1: Invest Ophthalmol Vis Sci. 2010 Mar 10; [Epub ahead of print] 

Increased fundus autofluorescence in neovascular age-related macular
degeneration is associated with outer segment shortening in macular
translocation model.

Chen FK, Patel PJ, Coffey PJ, Tufail A, Da Cruz L.

Vitreoretinal Surgery, Moorfields Eye Hospital, London, United Kingdom.

Purpose: To report the frequency and origins of increased fundus
autofluorescence (AF) in age-related macular degeneration using the model of
macular translocation. Methods: In this retrospective observational case series,
post-operative serial fundus AF images from 40 consecutive patients were
examined. The origin of well-delineated increased AF changes was explored by
examining simultaneous spectral-domain optical coherence tomography (SD-OCT)
scans and co-registered microperimetry. Results: AF images were taken between a
mean of 13 and 36 months. A total of 7 eyes were excluded from analysis due to
lack of post-operative AF imaging or extensive macular RPE atrophy. Of the
remaining, 9 had masking of foveal AF pattern, 21 had small round increased AF
lesions in the fovea and 3 had a near normal pattern of foveal hypo-AF.
Parafoveal increased AF was seen in all 33 patients in 1 of 3 patterns:
well-delineated homogenous increased AF patches (17), curvilinear increased AF
bands (4) and speckled increased AF (12). Simultaneous SD-OCT showed loss of
signal from the interface of the inner and outer segments (OS) of the
photoreceptor cell layer with variable loss of outer nuclear layer thickness.
Microperimetry showed subnormal retinal sensitivity in regions with increased
AF. Parafoveal increased AF size remained stable during 2-5 years of follow-up.
Conclusions: SD-OCT and microperimetry changes observed after translocation may
be due to shortening of the OS. A corresponding reduction of visual pigment in
the shortened OS may lead to unmasking effect. Increased AF in some macular
diseases may be due to unmasking of AF rather than increased fluorophores within
abnormal retina.

PMID: 20220058  [PubMed - as supplied by publisher]

2: Invest Ophthalmol Vis Sci. 2010 Mar 10; [Epub ahead of print] 

Role of Matrix Metalloproteinase-9 in the Development of Diabetic Retinopathy
and its Regulation by H-Ras.

Kowluru RA.

Ophthalmology, Wayne State University, Detroit, United States.

Objective: Diabetes activates small molecular weight G-protein, H-Ras, in the
retina and its capillary cells, and H-Ras activation is implicated in the
apoptosis of retinal capillary cells. Matrix metalloproteinase-9 (MMP-9) is
regulated by H-Ras, and in diabetes its activation is associated with increased
vascular permeability. The goal of this study is to investigate the role of
sustained activation of MMP-9 in the pathogenesis of diabetic retinopathy, and
illustrate the mechanism via which it is upregulated in diabetes. Methods:
Retinal MMP-9 activation and its tissue inhibitor-TIMP-1, were quantified in
streptozotocin-induced diabetic rats. Inhibition of H-Ras by simvastatin on
diabetes-induced activation of H-Ras was evaluated. The mechanism via which
diabetes regulates retinal MMP-9 was confirmed by determining the effect of
genetic or pharmacologic regulation of H-Ras on its activation in retinal
endothelial cells. Results: In diabetic rats MMP-9 was activated and expression
of TIMP-1 decreased in the retina and its microvasculature at both 2 months and
12 months durations. In retinal endothelial cells, high glucose activated MMP-9,
and inhibition of its activation (by pharmacologic inhibitor or siRNA)
ameliorated accelerated apoptosis. Inhibition of H-Ras, both in diabetic rats
(simvastatin) and in isolated endothelial cells (H-Ras siRNA), abrogated the
activation of MMP-9 and prevented reduction in TIMP-1. Conclusions:
Hyperglycemia-induced activation of MMP-9 accelerates apoptosis of retinal
capillary cells, a phenomenon that predicts the development of diabetic
retinopathy, and the activation of MMP-9 is downstream of H-Ras. Characterizing
the role of MMP-9 in the development of diabetic retinopathy will help explore
novel molecular targets for future pharmacological interventions.

PMID: 20220057  [PubMed - as supplied by publisher]

3: Invest Ophthalmol Vis Sci. 2010 Mar 10; [Epub ahead of print] 

Apelin in Plasma and Vitreous and in Fibrovascular Retinal Membranes from
Patients with Proliferative Diabetic Retinopathy.

Tao Y, Lu Q, Jiang YR, Qian J, Wang JY, Gao L, Jonas JB.

Ophthalmology, People's Hospital, Peking University, Beijing, China.

Purpose: Apelin is an endogenous ligand for the angiotensin-1-like receptor APJ.
Since apelin has been reported to regulate angiogenesis, we searched for
associations between apelin and proliferative diabetic retinopathy (PDR).
Methods: The study included 55 patients undergoing vitrectomy for PDR (study
group), and of 34 patients undergoing vitrectomy for idiopathic pre-retinal
membranes or macular hole (control group). Using enzyme-linked immunosorbent
assay, we measured the concentrations of apelin and vascular endothelial growth
factor (VEGF) in the vitreous and plasma. The expression of apelin and
angiotensin-1-like receptor APJ in the excised membranes was examined by
fluorescence Immunostaining and semiquantitative reverse transcription
polymerase chain reaction. Results: Vitreous concentrations of apelin were
significantly higher in the study group than in the control group (P=0.005),
while plasma concentrations of apelin did not vary significantly (P=0.66). The
vitreous concentrations (P<0.001) and the plasma concentrations (P=0.03) of VEGF
were significantly higher in the study group than in the control group. Neither
the vitreous concentrations of apelin and VEGF (P=0.47) nor the plasma
concentrations of apelin and VEGF (P=0.19) were significantly associated with
each other. In the fibrovascular membranes of the study group, a co-localization
of the endothelial markers CD31 with the markers for apelin and a
co-localization of the endothelial markers CD31 and APJ was observed. Expression
of apelin mRNA (P=0.03), APJ mRNA (P=0.02) and VEGF mRNA (P<0.01) was
significantly higher in fibrovascular PDR membranes than in idiopathic
epiretinal membranes. Conclusions: The apelin/APJ system may be involved in
retinal neovascularization during the development of proliferative diabetic
retinopathy.

PMID: 20220056  [PubMed - as supplied by publisher]

4: Invest Ophthalmol Vis Sci. 2010 Mar 10; [Epub ahead of print] 

Intravitreous Delivery of the Corticosteroid FluocinoloneAcetonide Attenuates
Retinal Degeneration in S334ter-4 Rats.

Glybina IV, Kennedy A, Ashton P, Abrams G, Iezzi R.

Ophthalmology, Wayne State University, Kresge Eye Institute, Detroit, United
States.

Purpose: To study the neuroprotective properties of low-dose, sustained-release
intravitreous fluocinolone acetonide (FA) in transgenic S334ter-4 rats. Methods:
S334ter-4 rats aged 4 weeks were divided into four groups: 0.5mug/day FA-loaded
intravitreous drug-delivery implant (IDDI); 0.2mug/day FA-loaded IDDI; inactive
IDDI; and unoperated controls. Electroretinography (ERG) was performed
pre-operatively and every two weeks post-operatively for eight weeks. At 12
weeks of age, outer nuclear layer (ONL) and inner nuclear layer (INL)
thicknesses were measured. Microglial cell counts were obtained from retinal
wholemounts labeled for Iba-1. Results: At the end of the study, unoperated and
inactive IDDI-implanted rats demonstrated 50-60% reduction in ERG amplitudes
compared to the ERGs recorded at 4 weeks (p<0.001 for both groups). FA
0.2mug/day-animals demonstrated 15% amplitude attenuation, while FA
0.5mug/day-animals showed 30% reduction. ONL thickness in FA 0.2mug/day-treated
eyes was 25.8%+/-2.3% higher than in control group eyes (p<0.001) and
30.0%+/-2.1% higher than in inactive IDDI-implanted eyes (p<0.001). In FA
0.5mug/day-treated eyes, ONL thickness was 22.4%+/-2.8% higher than in control
group eyes (p<0.001) and 22.3%+/-3.7% higher than in inactive IDDI-implanted
eyes (p<0.01). No statistically significant difference was observed between the
two control groups. No statistically significant difference between the two
FA-treated groups was found. FA-treated groups demonstrated significantly fewer
activated microglial cells, as compared to control groups. Conclusion: Chronic
intravitreous infusion of FA preserves ONL cell morphology, ERG a- and b-wave
amplitudes, and reduces retinal neuroinflammation in S334ter rats. Based on
these findings, the synthetic corticosteroid FA may promise a therapeutic role
in patients with retinal degenerations.

PMID: 20220055  [PubMed - as supplied by publisher]

5: Invest Ophthalmol Vis Sci. 2010 Mar 10; [Epub ahead of print] 

High Resolution Fourier-Domain Optical Coherence Tomography of Choroidal
Neovascular Membranes Associated with Age-Related Macular Degeneration.

Park SS, Truong S, Zawadzki R, Alam S, Choi S, Telander DG, Werner J, Morse LS.

Ophthalmology, University of California Davis Eye Center, Sacramento, United
States.

Purpose: To investigate to use of high resolution Fourier-domain optical
coherence tomography (Fd-OCT) to image choroidal neovascular membranes (CNVM)
associated with exudative age-related macular degeneration (eAMD). Methods: An
Fd-OCT instrument with axial resolution of 4 to 4.5 mum and transverse
resolution of 10 to 15 mum was used to image 21 eyes (19 subjects) with
newly-diagnosed eAMD. A raster series of 100 B-scans separated by 60 mum was
used study the growth pattern of CNVM and associated morphologic changes. CNVM
size was determined using 250 to 300 serial virtual C-scans of reconstructed
3-dimensional macular volume. Results: A highly reflective subretinal and/or
sub-retinal pigment epithelial (RPE) lesion that co-localized with the CNVM seen
on fluorescein angiography was detected in all eyes using Fd-OCT. Although a
combined subretinal and sub-RPE growth pattern of varying degrees was noted in
15 eyes (71%), a statistically significant difference in the distribution of
growth pattern was noted when classic CNVM was compared to occult CNVM (chi2 =
10.4, df = 2, p < 0.005). Classic lesions had >90% subretinal growth pattern
while occult lesions had a more variable growth pattern. Angiographic CNVM size
correlated with size on Fd-OCT but correlation was better for classic CNVM
(r=0.99, p<0.0001 for classic; r=0.78, p<0.001 for non-classic). Conclusions:
Fd-OCT is a promising potential alternative modality to visualize CNVM with AMD.
Angiographic lesion size and type correlated with growth pattern and size of
CNVM on Fd-OCT with correlation being stronger for classic lesions.

PMID: 20220054  [PubMed - as supplied by publisher]

6: Invest Ophthalmol Vis Sci. 2010 Mar 10; [Epub ahead of print] 

Variable retinal phenotypes caused by mutations in the X-linked photopigment
gene array.

Mizrahi-Meissonnier L, Merin S, Banin E, Sharon D.

Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Purpose: To examine the involvement of the long (L) and middle (M)
wavelength-sensitive cone opsin genes in cone dominated phenotypes. Methods:
Clinical and molecular analyses included family history, color vision testing,
full-field electroretinography (ERG), linkage analysis, and mutation detection.
Results: We recruited 18 families with X-linked retinal disease characterized by
cone impairment in which affected males usually had nystagmus, reduced visual
acuity, normal to subnormal rod ERG, and reduced or extinguished cone ERG
responses. A search for mutations in the L-M pigment gene array revealed
disease-causing mutations in 6 families. In two of them, novel mutations were
identified: a large deletion affecting both opsin genes and a single L opsin
gene harboring a likely pathogenic mutation, p.Val120Met. A third family carried
a single hybrid gene with the p.Cys203Arg mutation. Interestingly, patients from
the three remaining families carried a single opsin gene harboring two similar
rare haplotypes. Although the phenotype of members in one of the families was
compatible with blue cone monochromacy (BCM), patients from the two other
families, who shared an identical haplotype, had only reduced or even normal
full field cone ERG but maculopathy was evident. Conclusions: We present here
novel and known mutations affecting the L-M opsin gene array in families with
X-linked cone-dominated phenotypes. Our results show that different mutations in
this gene array can cause a variety of phenotypes including BCM, cone dystrophy,
and maculopathy. We propose that males with X-linked cone-dominated diseases
should be routinely analyzed for mutations in the L-M opsin gene array.

PMID: 20220053  [PubMed - as supplied by publisher]

7: Invest Ophthalmol Vis Sci. 2010 Mar 10; [Epub ahead of print] 

Interferon Gamma-inducible Protein (IP-10) and Eotaxin Are Associated with
Age-related Macular Degeneration.

Mo FM, Proia AD, Johnson WH, Cyr D, Lashkari K.

Schepens Eye Research Institute, Harvard Medical School, Boston, United States.

Purpose: To analyze serum cytokine levels in subjects with different stages of
AMD and to study the expression of salient cytokines in postmortem eyes with
AMD. Methods: A Bio-Plex system was used to analyze sera (n = 18 to 20/group)
from control subjects and those with AREDS stage 1 (early AMD), AREDS stage 3
(intermediate AMD), advanced AMD with geographic atrophy (GA), or neovascular
AMD (CNV). Postmortem eyes with AMD or controls were examined
immunohistochemically for expression of IP-10 and eotaxin (n = 4 to 8/group).
Results: Serum eotaxin and IP-10 levels were significantly elevated in all
stages of AMD except for eotaxin levels in neovascular AMD (P<0.07). The peak of
serum IP-10 concentration was at AREDS stage 3. In postmortem eyes, IP-10 and
eotaxin expressions were increased in the RPE of eyes with early AMD, GA, and
CNV. Eotaxin accumulated within the layer of basal linear/laminar deposits in
all stages of AMD, while IP-10 was mainly in eyes with GA and CNV. IP-10 was
abundant in the connective tissue matrix associated with CNV, and eotaxin was
usually present but more focally and with less intense staining. Both IP-10 and
eotaxin were expressed by neovascular endothelial cells. Both IP-10 and eotaxin
were expressed in the neurosensory retina, but there was no detectable
difference in staining among eyes with or without AMD. Conclusions: IP-10 and
eotaxin may be early biomarkers in AMD, and we hypothesize that the relative
balance between levels of IP-10 and eotaxin may be critical in regulating the
neovascular response.

PMID: 20220052  [PubMed - as supplied by publisher]

8: Invest Ophthalmol Vis Sci. 2010 Mar 10; [Epub ahead of print] 

Optical Defocus Influences Refractive Development in Monkeys via Local,
Regionally Selective Mechanisms.

Smith EL, Hung LF, Huang J, Blasdel TL, Humbird TL, Bockhorst KH.

University of Houston, College of Optometry, Houston, United States.

PURPOSE. To characterize the influence of optical defocus on ocular shape and
the pattern of peripheral refractions in infant rhesus monkeys. METHODS.
Starting at 3 weeks of age, 8 infant monkeys were reared wearing -3 D spectacle
lenses over one eye that produced relative hyperopic defocus in the nasal field,
but allowed unrestricted vision in the temporal field (NF group). Six infants
were reared with monocular -3 D lenses that produced relative hyperopic defocus
across the entire field of view. Control data were obtained from 11 normal
monkeys. Refractive development was assessed by streak retinoscopy performed
along the pupillary axis and at eccentricities of 15 degrees , 30 degrees and 45
degrees along the vertical and horizontal meridians. Central axial dimensions
and eye shape were assessed with magnetic resonance imaging (MRI). RESULTS. In
response to full-field hyperopic defocus, the eye developed relative central
axial myopia, became less oblate in shape, and exhibited relative peripheral
hyperopia in both the nasal and temporal hemifields. On the other hand,
nasal-field hyperopic defocus produced relative myopia that was largely
restricted to the nasal hemifield; these alterations in the pattern of
peripheral refractions in the NF monkeys were associated with local,
region-specific alterations in vitreous chamber depth in the treated
hemi-retina. CONCLUSIONS. Optically imposed defocus can alter the shape and
pattern of peripheral refractions in infant primates. Like form deprivation, the
effects of optical defocus in primates are dominated by mechanisms that
integrate visual signals in a spatially restricted manner and exert their
influence in a regionally selective manner.

PMID: 20220051  [PubMed - as supplied by publisher]

9: Invest Ophthalmol Vis Sci. 2010 Mar 10; [Epub ahead of print] 

Changes in fibroblast mechanostat set point and mechano-sensitivity suggest an
adaptive response to mechanical stress in Floppy Eyelid Syndrome.

Ezra DG, Ellis JS, Beaconsfield M, Collin R, Bailly M.

Moorfields Eye Hospital and UCL Institute of Ophthalmology, NIHR Biomedical
Research Centre for Ophthalmology, London, United Kingdom.

Purpose: Floppy eyelid syndrome (FES) is an acquired hyperelasticity disorder
affecting the upper eyelid. The tarsal plate becomes hyperelastic with a loss of
intrinsic rigidity. As a result, the eyelid is subjected to cyclic mechanical
stress. This condition was used as a model to investigate changes in dynamic
fibroblast contractility in the context of chronic cyclic mechanical stress.
Methods: Contractile efficiency was investigated using a free floating 3
dimensional collagen matrix model. Intrinsic cellular force measurements and
responses to changes in gel tension were explored using a tensioning culture
force monitor (t-CFM). Gene expression differences between cell lines exhibiting
differences in contractile phenotype were explored using a genome level
microarray platform and RT-PCR. Results: FES Tarsal plate fibroblasts (TFs)
showed an increased contractile efficiency compared to control cells and t-CFM
measurements confirmed a higher intrinsic cellular force at plateau levels.
Cyclic stretch/relaxation experiments determined that TFs in FES maintained a
functional tensional homeostasis response but with an altered sensitivity,
operating around a higher mechanostat set point. Gene expression array and
RT-PCR analysis identified V-CAM1 and PPP1R3C as being upregulated in FES TFs.
Conclusion: We propose that these changes represent an adaptive response that
allows tensional homeostasis to be maintained at the high levels of tissue
stress experienced in FES. Gene expression studies point to a role for V-CAM1
and PPP1R3C in mediating changes in the dynamic range of mechanosensitivity of
TFs. This work identifies FES as a useful model to study adaptive physiological
responses to mechanical stress.

PMID: 20220050  [PubMed - as supplied by publisher]

10: Invest Ophthalmol Vis Sci. 2010 Mar 10; [Epub ahead of print] 

Gene Expression Profile of Hyperoxic/Hypoxic Retinas in Mouse Model of
Oxygen-induced Retinopathy.

Ishikawa K, Yoshida S, Kadota K, Nakamura T, Niiro H, Arakawa S, Yoshida A,
Akashi K, Ishibashi T.

Ophthalmology, Kyushu University, Fukuoka, Japan.

PURPOSE. To determine a profile of gene expression in retinas of a murine model
of oxygen-induced retinopathy (OIR). METHODS. OIR was induced in C57BL/6N mice
by exposing postnatal day 7 (P7) pups to 75% oxygen for 5 days, and then
returning them to room air at P12. Gene microarrays containing more than 47,000
transcripts were used to study the changes in gene expression in retinas
isolated immediately (P12) and at 12 hours (P12.5) after the hyperoxic exposure.
The retinas of P12 mice raised under normoxic conditions served as controls.
Quantitative RT-PCR and multiplex ELISA were performed to validate the
microarray analyses. RESULTS. The expression of 83 gene transcripts were
significantly altered in the hyperoxic P12 retinas. These genes were classified
into cellular components, development, metabolism, transport, stress response,
cell adhesion, inflammation, and vision. The genes related to retinal growth,
such as Pdgfb and Robo4 which are associated with vascular development, were
down-regulated. In contrast, the expression levels of 95 genes were
significantly altered in the hypoxic P12.5 retinas which contained several known
hypoxia-regulated genes including Vegfa and Hif1alpha. The differentially
expressed genes could be broadly clustered into development, inflammation,
metabolism, signaling, anti-apoptosis, cellular component, transport,
glycolysis, and vision. The genes related to organogenesis, e.g., Vegfa, Igfbp3,
Tnfrsf12a, and Nestin, and to inflammation e.g., Ccl3, Ccl4, and MHCs, were
up-regulated. The results of quantitative RT-PCR and multiplex ELISA were in
agreement with the microarray data. CONCLUSIONS. These alterations in gene
expression may determine the hyperoxic growth retardation, post-ischemic
inflammation, neovascularization, and remodeling in retinas of murine OIR.

PMID: 20220049  [PubMed - as supplied by publisher]

11: Invest Ophthalmol Vis Sci. 2010 Mar 10; [Epub ahead of print] 

A Comparison of Visual Field Sensitivity to Photoreceptor Thickness in Retinitis
Pigmentosa.

Rangaswamy NV, Patel HM, Locke KG, Hood DC, Birch DG.

Retina Foundation of Southwest, Dallas, United States.

Purpose: To explore the relationship between visual field sensitivity and
photoreceptor layer thickness in patients with retinitis pigmentosa (RP).
Methods: Static automated perimetry with Humphrey Field Analyzer (central 30-2
threshold program with spot size III) and frequency domain optical coherence
tomography (fd-OCT) scans with Spectralis HRA+OCT were obtained from 10
age-matched normal controls and 20 patients with RP retaining good central
vision (better than 20/32). The OS+ thickness [the distance between retinal
pigment epithelium (RPE)/Bruch's membrane (BM) to the photoreceptor inner-outer
segment junction], outer nuclear layer (ONL) and total retinal thickness were
measured at locations corresponding to visual field test loci up to 21 degrees
eccentricity. Results: The average OS+ thickness in the control eyes was 63.1
+/- 5.2 mum, varying from approximately 69 mum in the foveal center to 56 mum at
21 degrees eccentricity. In patients with RP, OS+ thickness was below normal
limits outside the fovea, and thickness decreased with loss in local field
sensitivity, reaching an asymptotic value of 21.5 mum at about -10 dB. The ONL
thickness also decreased with local field sensitivity loss. While relative OS
thickness was linearly related to visual field loss at all locations examined, a
slightly better correlation was found between the product of OS and ONL
thickness and visual field loss. Conclusion: In patients with RP with good
foveal sensitivity, the OS thickness and the product of OS thickness and ONL
thickness (assumed to represent number of photoreceptor) decreases linearly with
loss of local field sensitivity. In general, in regions where perimetric
sensitivity loss is -10 dB or worse, the OS+ thickness approaches the thickness
of the RPE/BM complex.

PMID: 20220048  [PubMed - as supplied by publisher]

12: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Effects of Bone Marrow Mesenchymal Stem Cells Transplantation on Light-Damaged
Retina.

Zhang Y, Wang W.

Peking University Third Hospital, Peking University Eye Center, Beijing, China.

Purpose: to investigate the effects and possible mechanisms of rat bone marrow
mesenchymal stem cells (BMSCs) transplantation on light-damaged retinal
structure and the apoptosis of photoreceptors. Methods: 4' 6- diamidino
-2-phenylindole (DAPI)-labeled BMSCs were transplanted into the subretinal space
of light-damaged Sprague-Dawley (SD) rats 10 days after exposure. BMSCs were
cultivated with the supernatant of homogenized retina (SHR). Results: Compared
with the phosphate buffered solution (PBS) injection group and the light damage
group, the outer nuclear layer (ONL) contained significantly more cells and the
percentage of apoptotic ONL cells was significantly reduced in the BMSCs
transplantation group. Most DAPI-labeled BMSCs expressed brain-derived
neurotrophic factor (BDNF). There was elevated basic fibroblast growth factor
(bFGF) and BDNF immunoreactivity in the retinas of the BMSCs transplantation
group, as compared with the light damage group. In vitro culture showed that 10%
BMSCs changed from fusiform shape to multipolar shape. A fraction of cells
expressed MAP2 or GFAP, and some cells expressed bFGF or BDNF when cultivated
with light-damaged SHR for 7 days. Conclusion: BMSCs subretinal transplantation
could inhibit photoreceptors apoptosis and slow down retinal damage in
light-damaged eyes. BMSCs could express bFGF (in vitro) and BDNF (in vitro and
in vivo), pointing to potential trophic and protective effects on light-damaged
retinas.

PMID: 20207980  [PubMed - as supplied by publisher]

13: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Prevalence of Amblyopia and Strabismus in Young Singaporean Chinese children.

Chia A, Dirani M, Chan YH, Gazzard G, Au Eong KG, Selvaraj P, Ling Y, Quah BL,
Young T, Mitchell P, Varma R, Wong TY, Saw SM.

Paediatric Services, Singapore National Eye Centre, Singapore, Singapore.

Purpose: To determine the prevalence of amblyopia and strabismus in young
Singapore Chinese children. Methods: 3009 Singaporean children, aged 6 -72
months, underwent complete eye examinations and cycloplegic refraction. Visual
acuity (VA) was measured with logMAR chart when possible, and Sheridan Gardner
test when not. Strabismus was defined as any manifest tropia. Unilateral
amblyopia was defined as a 2-line difference between eyes with VA<20/30 in the
worse eye, and with coexisting anisometropia (>/=1.00D for hyperopia, >/=3.00D
for myopia, >/=1.50D for astigmatism), strabismus or past/present visual axis
obstruction. Bilateral amblyopia was defined as VA in both eyes <20/40 (in
children 48-72months) and <20/50 (<48months), with coexisting hyperopia >/=
4.00D, myopia /=2.50D, or past/present visual axis
obstruction. Results: The amblyopia prevalence in children aged 30 to 72 months
was 1.19% (95% confidence interval, CI, 0.73-1.83) with no age (p=0.37) or
gender (p=0.22) differences. Unilateral amblyopia (0.83%) was twice as frequent
as bilateral amblyopia (0.36%). The most frequent causes of amblyopia were
refractive error (85%) and strabismus (15%); anisometropic astigmatism >1.50D
(42%) and isometropic astigmatism >2.50D (29%) were frequent refractive errors.
The prevalence of strabismus in children aged 6 to 72 months was 0.80% (95%CI
0.51-1.19), with no gender (p=0.52) or age (p=0.08) effects. The exotropia:
esotropia ratio was 7:1 with most exotropia being intermittent (63%). Of
children with amblyopia, 15.0% had strabismus, while 12.5% of children with
strabismus had amblyopia. Conclusion: The prevalence of amblyopia was similar
while the prevalence of strabismus was lower than in other populations.

PMID: 20207979  [PubMed - as supplied by publisher]

14: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Correlation of relative afferent pupillary defect and retinal nerve fiber layer
loss in unilateral or asymmetrical demyelinating optic neuropathy.

Younis A, Eggenberger E.

Neurology and Ophthalmology, Michigan State University, East lansing, United
States.

PURPOSE: To investigate the relationship between the relative afferent pupillary
defect (RAPD) and retinal nerve fiber layer (RNFL) thickness assessed by optical
coherence tomography (OCT) in patients with unilateral or asymmetrical
demyelinating optic neuropathy. METHODS: Seventy-two patients with unilateral or
asymmetrical demyelinating optic neuropathy were retrospectively evaluated. The
RAPD was measured by the swinging flashlight method using neutral density
filters, and RNFL thickness was measured with the Stratus OCT. Relationships
between the RAPD and RNFL thickness difference/ ratio between the two eyes (in
superior, inferior, temporal, nasal quadrants and total thickness) were
evaluated by linear regression. Coefficients of determination (R2) were
calculated using a multivariate model. RESULTS: The mean RNFL thickness in the
more affected eyes was 82.7 +/- 18.7microm and in the fellow eyes was 88.9 +/-
13.97microm (R2 = 0.406, P < 0.0001). The RAPD size correlated significantly
with both RNFL thickness difference (total: R2 = 0.191, P < 0.0001, superior: R2
= 0.203, P < 0.0001, inferior: R2 = 0.126, P= 0.002, temporal: R2 = 0.059,
P=0.040, nasal: R2 = 0.062, P= 0.035) and RNFL thickness ratio ( total: R2 =
0.325, P = 0.0001, superior : R2 = 0.339, P < 0.0001, inferior: R2 = 0.256, P <
0.0001, temporal: R2 = 0.151, P = 0.0001, nasal: R2 = 0.156, P= 0.001).
CONCLUSIONS: The RAPD as measured in log units significantly correlated with the
total and quadrantic RNFL thickness differences and ratios; the total, superior
and inferior quadrant data produced the strongest correlations.

PMID: 20207978  [PubMed - as supplied by publisher]

15: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

FLUOROPHOTOMETRIC STUDY OF THE EFFECT OF the GLAUKOS TRABECULAR MICRO-BYPASS
STENT ON AQUEOUS HUMOR DYNAMICS.

Fernandez-Barrientos Y, Garcia-Feijoo J, Martinez de la Casa JM, Pablo LE,
Fernandez-Perez C, Garcia Sanchez J.

Instituto de Investigaciones Ramon Castroviejo, Hospital Clinico Universitario
San Carlos, Madrid, Spain.

Purpose: To evaluate the changes in aqueous humor dynamics and the efficacy and
safety of the iStent(R) in combination with cataract surgery. Methods:
Prospective, randomized, clinical study in patients with open-angle glaucoma or
ocular hypertension, undergoing cataract surgery. Aqueous flow (F) and
trabecular outflow facility (CT) was measured by fluorophotometry preoperatively
and at months 1, 6 and 12 in both groups. Results: Thirty-three eyes of 33
patients were randomized to either two stents and cataract surgery (n=17, Group
1) or cataract surgery alone (n=16, Group 2). Preoperatively, F and CT were
similar in Groups 1 and 2 (1.78 +/- 0.44 and 1.74 +/- 0.82 microl/min, p=0.18;
0.12 +/- 0.03 and 0.13 +/- 0.06 microl/min/mmHg, p=0.71, respectively).
Postoperatively, there were no changes of note in F, however, CT increased in
both groups. At one year, CT was 0.45+/-0.27 microl/min/mmHg in Group 1 and
0.19+/-0.05 microl/min/mmHg in Group 2 (p=0.02), which represented increases of
275% and 46%, respectively. Mean IOP reduction was also greater in Group 1 than
in Group 2 (6.6 +/- 3.0 vs. 3.9 +/- 2.7 mmHg; p=0.002). The mean number of
medications was significantly lower in Group 1 vs. Group 2 (0.0 vs. 0.7 +/- 1.0,
respectively; p=0.007). Conclusions: Compared with cataract surgery alone,
implantation of the iStent(R) concomitant with cataract extraction significantly
increased the trabecular outflow facility, achieved IOP reduction, and reduced
the number of medications at one year. Longer follow-up is needed to assess the
long-term effect on outflow facility.

PMID: 20207977  [PubMed - as supplied by publisher]

16: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Use of single-vision distance spectacles improves landing control during step
descent in well-adapted multifocal lens-wearers.

Timmis MA, Johnson L, Elliott DB, Buckley JG.

Division of Medical Engineering, School of Engineering Design & Technology,
University of Bradford, Bradford, United Kingdom.

Purpose: Epidemiological research has shown that multifocal spectacle wearers
(bifocal and progressive addition lenses, PALs) are more than twice as likely to
fall compared with non-multifocal spectacle wearers with this risk further
increasing when negotiating stairs. The present study investigated whether
step/stair descent safety is improved by using single-vision distance lenses.
Methods: From a stationary standing position on top of a block, twenty long-term
multifocal wearers stepped down (from different block heights) onto a lower
level wearing either bifocal, PALs or single-vision distance lenses. Results:
Use of single-vision distance spectacles lead to an increased single-limb
support time, a reduced ankle and knee angle and vertical centre-of-mass
velocity at contact with the lower level, and a reduced ankle angular velocity
and vertical centre-of-mass velocity during initial landing (p < 0.03). These
findings indicate that landing occurred in a more controlled manner when wearing
single-vision distance spectacles, rather than tending to 'drop' onto the lower
level as occurred when wearing bifocals or PALs. Conclusion: Use of
single-vision distance spectacles lead to improvements in landing control,
consistent with individuals being more certain regarding the precise height of
the lower floor level. This was attributed to having a view of the foot, step
edge and immediate floor area that was not blurred, magnified or doubled and
that did not suffer from image jump or peripheral distortions. These findings
provide further evidence that use of single-vision distance lenses in everyday
locomotion may be advantageous for elderly multifocal wearers who have a high
risk of falling.

PMID: 20207976  [PubMed - as supplied by publisher]

17: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Ocular Risk Factors for Choroidal Neovascularization in Pathological Myopia.

Ikuno Y, Jo Y, Hamasaki T, Tano Y.

Ophthalmology, Osaka University Medical School, Suita, Japan.

PURPOSE. To identify the risk factors for development of myopic choroidal
neovascularization (mCNV), a major cause of visual impairment. METHODS. We
included 23 consecutive patients with bilateral high myopia (axial length
>/=26.5 mm or refractive error PMID: 20207975  [PubMed - as supplied by publisher]

18: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Histamine reduces flash sensitivity of ON retinal ganglion cells in primate
retina.

Akimov NP, Marshak DW, Frishman L, Glickman RD, Yusupov RG.

Physiology, University of Texas Health Science Center, San Antonio, United
States.

Purpose. In Old World primates, the retina receives input from histaminergic
neurons in the posterior hypothalamus. They are a subset of the neurons that
project throughout the central nervous system and fire maximally during the day.
In order to learn how they contribute to vision, we applied histamine to a dark
adapted, superfused baboon eyecup preparation while recording extracellularly
from peripheral retinal ganglion cells. Methods. The stimuli were 5 ms, 560 nm,
weak, full-field flashes in the low scotopic range. Ganglion cells with
sustained and transient ON responses and two cell types with OFF responses were
distinguished; their responses were recorded with a 16-channel microelectrode
array. Results. Low micromolar doses of histamine decreased the rate of
maintained firing and the light sensitivity of ON ganglion cells. Both sustained
and transient ON cells responded similarly to histamine. There were no
statistically significant effects of histamine in a more limited study of OFF
ganglion cells. The response latencies of ON cells were about 5 ms slower, on
average, when histamine was present. Histamine also reduced the signal to noise
ratio of ON cells, particularly for those cells whose maintained activity was
increased by histamine. Conclusions. A major action of histamine released from
retinopetal axons under dark adapted conditions, when rod signals dominate the
response, is to reduce the sensitivity of ON ganglion cells to light flashes.
These findings may relate to reports that humans are less sensitive to light
stimuli in the scotopic range during the day, when histamine release in the
retina is expected to be maximal.

PMID: 20207974  [PubMed - as supplied by publisher]

19: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

A comparison of rates of change in neuroretinal rim area and retinal nerve fiber
layer thickness in progressive glaucoma.

Alencar LM, Zangwill LM, Weinreb RN, Bowd C, Sample PA, Girkin CA, Liebmann JM,
Medeiros FA.

Hamilton Glaucoma Center, University of California, San Diego, La Jolla, United
States.

Purpose: To evaluate and compare rates of change in neuroretinal rim area (RA)
and retinal nerve fiber layer thickness (RNFLT) measurements in glaucomatous
patients, glaucoma suspects, and normals followed over time. Methods:
Observational cohort study including patients recruited from two longitudinal
studies (Diagnostic Innovations in Glaucoma Study-DIGS and African Descent and
Evaluation Study-ADAGES), which were followed with standard achromatic perimetry
(SAP), optic disc stereophotographs, confocal scanning laser ophthalmoscopy
(HRT-3) and scanning laser polarimetry (GDx-VCC) imaging. Progression was
determined by the Guided Progression Analysis software for SAP and by masked
assessment of serial optic disc stereophotographs by expert graders. Random
coefficient models were used to evaluate rates of change in average RNFLT and
global RA measurements and their relationship with glaucomatous progression.
Results: At baseline, 194 (31%) eyes were glaucomatous; 347 (55%) were suspects
and 88 (14%) were normals. Forty-six eyes (9%) showed progression by SAP and/or
stereophotographs, during an average follow-up of 3.3 (+/-0.7) years. The
average rate of decline for RNFLT measurements was significantly higher in the
progressing group compared to the non-progressing group (-0.65mum/year vs.
-0.11mum/year, respectively; P<0.001), whereas for RA it was not significantly
different between these groups (-0.0058mm(2)/year vs. -0.0073mm(2)/year,
respectively; P=0.727). The areas under the receiver operating characteristic
curves (ROC) used to discriminate progressing versus non-progressing were 0.811
and 0.507, for the rates of change in RNFLT and RA, respectively (P<0.001).
Conclusion: The ability to discriminate eyes progressing by SAP and/or
stereophotographs from stable eyes was significantly greater for RNFLT compared
to RA measurements.

PMID: 20207973  [PubMed - as supplied by publisher]

20: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Influence of Corneal Collagen Crosslinking With Riboflavin and Ultraviolet-A
Irradiation on Excimer Laser Surgery.

Kampik D, Ralla B, Keller S, Hirschberg M, Friedl P, Geerling G.

Department of Ophthalmology, University of Wuerzburg, Wuerzburg, Germany.

Purpose: Riboflavin/UVA crosslinking (CXL) of corneal collagen is a novel method
to stabilize corneal mechanical properties and prevent progression of
keratectasias. The study investigates whether CXL influences ablation rate, flap
thickness and refractive results of Excimer laser procedures ex vivo. Methods:
In enucleated porcine eyes corneal epithelium was removed and CXL performed with
riboflavin 0.1% and UVA radiation (365nm, 3mW/cm(2)) for 30min. Controls
received epithelial abrasion only. Diffusion of riboflavin through the cornea
was assessed using infrared-excited 2-photon microscopy of riboflavin
autofluorescence combined with second harmonic generation of fibrillar collagen.
During phototherapeutic keratectomy corneal thickness was measured by optical
coherence pachymetry. During myopic LASIK flap thickness of microkeratome cuts
was measured and the induced refractive change assessed by Placido topography.
Data were analyzed by Shapiro-Wilk test and Student's t-test. Results:
Multiphoton-imaging showed a rapid (30min) and even distribution of riboflavin
throughout the corneal stroma. No difference in ablation rate was measured in
treated and untreated corneas (p=0.90). Mean flap thickness was increased by 44%
in crosslinked corneas (p<0.01). After myopic LASIK for 4 dpt up to 25 dpt, mean
corneal refractive change was reduced in CXL-treated eyes by 20.1% (p<0.05).
This effect was less pronounced in thinner flaps. Conclusion: CXL reduces the
amount of refractive change after myopic LASIK. While laser ablation rate is
unaffected, CXL results in an increased flap thickness. This study suggests a
need for adjustment of microkeratome and laser parameters for LASIK after CXL
and indirectly endorses the theory of a direct stiffening effect of CXL.

PMID: 20207972  [PubMed - as supplied by publisher]

21: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Surface topographies of glaucoma drainage devices and their influence on human
tenon fibroblast adhesion.

Choritz L, Koynov K, Renieri G, Barton K, Pfeiffer N, Thieme H.

BiomaTiCS Research Group, Department of Ophthalmology, University Medical Center
Mainz, Mainz, Germany.

Purpose: This study was performed to investigate the surface topography of
different glaucoma drainage devices, and the effects of surface roughness on
cell adhesion of cultured human tenon fibroblasts. Methods: The surface
topography of four widely used devices (Ahmed FP7, Ahmed S-2, Baerveldt 350,
Molteno S1) was investigated by scanning electron microscopy, roughness was
quantified using white light confocal microscopy. Cells were grown for 72 hours
on the surfaces of implants fixed to standard culture dishes. Cells were
labelled with a fluorescent dye and detected using confocal laser scanning
microscopy, while simultaneously imaging the surface reflectance. Collagen
adsorption was quantified immunologically using fluorescent beads coupled to
secondary antibody. Results: The root-mean-square roughness was 1.5 +/- 0.1
microm (mean +/- SE) for the silicone Ahmed model (FP7) and 1.3 +/- 0.1 microm
for the polypropylene base plate (S-2). The Baerveldt was substantially smoother
with a mean roughness of 0.1 +/- 0.01 microm. The Molteno was the smoothest of
all devices (0.07 +/- 0.01 microm). Cell adhesion was most profound on base
plates with higher surface roughness, markedly less pronounced on the smoother
base plates, and independent of collagen adsorption. Conclusions: This study
shows that the most frequently implanted glaucoma drainage devices are of
markedly different surface topography. Surface roughness appears to correlate
with tenon fibroblast adhesion in vitro and also with the rate of occurrence of
post-implantation hypertensive phase and failure due to fibrous encapsulation.
Surface roughness may thus play a role in triggering excessive fibrovascular
reactions. Smoother base plate surfaces might enhance success rates of these
devices.

PMID: 20207971  [PubMed - as supplied by publisher]

22: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Identification of novel substrates for the serine protease HTRA1 in the human
RPE secretome.

An E, Sen S, Park SK, Gordish-Dressman H, Hathout Y.

Institute of Biomedical Science, Program in Biochemistry and Molecular Genetics,
The George Washington University, Washington, United States.

PURPOSE. To define a role of the serine protease HTRA1 in Age-related Macular
Degeneration (AMD) by examining its expression level and identifying its
potential substrates in the context of primary RPE cell extracellular milieu.
METHODS. Primary RPE cell cultures were established from human autopsy eyes and
screened for CFH, ARMS2 and HTRA1 risk genotypes using TaqMan assay. HTRA1
expression in genotyped RPE cells was determined using real time PCR and
quantitative proteomics. Potential HTRA1 substrates were identified by
incubating RPE conditioned media with or without human recombinant HTRA1.
Selectively cleaved proteins were quantified using differential stable isotope
labeling by amino acids in cell culture strategy. RESULTS. HTRA1 mRNA levels
were 3 fold higher in primary RPE cells homozygous for the HTRA1 promoter risk
allele than in RPE cells with the wild type allele. This translated into a 2
fold increase in HTRA1 secretion by RPE cells with the risk genotype. A total of
196 extracellular proteins were identified in the RPE secretome and only 8 were
found selectively cleaved by the human recombinant HTRA1. These include
fibromodulin with 90% cleavage, clusterin (50%), ADAM9 (54%), vitronectin (54%)
and alpha 2 macroglobulin (55%) as well as some cell surface proteins including
talin-1 (21%), fascin (40%) and chloride intracellular channel protein 1 (51%).
CONCLUSIONS. Recombinant HTRA1 cleaves RPE secreted proteins involved in
regulation of the complement pathway (clusterin, vitronectin and fibromodulin)
and of amyloid deposition (clusterin, alpha 2 macroglobulin and ADAM9). These
findings suggest a potential link between HTRA1, complement regulation and
amyloid deposition in AMD pathogenesis.

PMID: 20207970  [PubMed - as supplied by publisher]

23: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

The Role of TLR4 in Photoreceptor {alpha}A Crystallin Upregulation During Early
EAU.

Saraswathy S, Nguyen AM, Rao NA.

Ophthalmology, Doheny Eye Institute, Los angeles, United States.

PURPOSE: Previous studies indicate that upregulation of alphaA crystallin
prevents photoreceptor mitochondrial oxidative stress mediated apoptosis in EAU.
In this study, the role of TLR4 was investigated in the upregulation of alphaA
crystallin in the retinas of animals with EAU. METHODS: TLR4-/-, iNOS -/-,
TNF-alpha -/-, MyD88 -/-, wild type (WT) control (C57BL/6) animals, and Nude
mice (B6.Cg-Foxn1nu) were immunized with IRBP mixed with complete Freund's
adjuvant; eyes were enucleated on day 7 post immunization. Real-time polymerase
chain reaction was first used to detect upregulated inflammatory cytokines and
alphaA crystallin in retinas with EAU; confirmed with Western blot, and the site
of upregulation was localized by immunohistochemistry. Oxidative stress was
localized using 8-OHdG and TUNEL staining was used to detect apoptosis. RESULTS:
In early EAU, increased expression of TNF-alpha, iNOS, and alphaA crystallin
genes were detected in the retinas of WT mice, whereas such upregulation was
absent in TLR4-deficient mice (P<0.001). alphaA crystallin was not elevated in
MyD88-/-,TNF-alpha -/- and iNOS-/- mice with EAU. Immunostains revealed
TNF-alpha, iNOS, and alphaA crystallin localization in the photoreceptor inner
segments and outer plexiform layer in the WT controls with EAU; but such
staining was absent in TLR4-deficient mice with EAU. 8-OHdG staining showed
oxidative stress in the photoreceptors in WT mice with EAU and there was no
apoptosis. CONCLUSIONS: TLR4 plays an important role in the upregulation of
alphaA crystallin through the interaction of MyD88 and subsequent generation of
TNF-alpha and iNOS in the EAU retina. Such crystallin upregulation may prevent
oxidative stress mediated apoptosis of photoreceptors in uveitis.

PMID: 20207969  [PubMed - as supplied by publisher]

24: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Reading strategies in mild to moderate strabismic amblyopia: an eye movement
investigation.

Kanonidou E, Proudlock FA, Gottlob I.

Ophthalmology, University of Leicester, Leicester, United Kingdom.

Purpose. To investigate oculomotor strategies in strabismic amblyopia and
evaluate abnormalities during monocular and binocular reading. Methods. Eye
movements were recorded using a head-mounted infrared video eye-tracker (250Hz,
<0.01 degrees resolution) in twenty strabismic amblyopes (mean age 44.9+/-10.7
years) and twenty normal controls (mean age 42.8+/-10.9 years) whilst silently
reading text paragraphs. Monocular reading comparisons were made between the
amblyopic eye versus non-dominant eye of controls, non-amblyopic eye versus
dominant eye of controls. Binocular reading between the amblyopic and controls
was also compared. Results. Mean reading speed, numbers of progressive and
regressive saccades per line, saccadic amplitude (of progressive saccades) and
fixation duration were estimated. Inter- and intra-subject statistical
comparisons were made. Reading speed was significantly slower in amblyopes
compared to controls during monocular reading with amblyopic (13.094
characters/s v 22.188 characters/s, p<0.0001) and non-amblyopic eyes (16.241
characters/s v 22.349 characters/s, p<0.0001), and binocularly (15.698
characters/s v 23.425 characters/s, p<0.0001). In amblyopes, reading was
significantly slower with the amblyopic eye compared to non-amblyopic eye and
binocular viewing (p<0.05). These differences were associated with significantly
more regressive saccades and longer fixation durations but not with changes in
saccadic amplitudes. Conclusions. In strabismic amblyopia, reading is impaired,
not only under monocular viewing with amblyopic eye, but also with non-amblyopic
eye and binocularly, even though normal visual acuity pertains to the latter two
conditions. The impaired reading performance is associated with differences in
both saccadic and fixational patterns most likely as adaptation strategies to
abnormal sensory experiences such as crowding and suppression.

PMID: 20207968  [PubMed - as supplied by publisher]

25: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Gene Expression within the Amacrine Cell Layer of Chicks Following Myopic and
Hyperopic Defocus.

Ashby RS, Feldkaemper MP.

Section of Neurobiology of the Eye, Institute for Ophthalmic Research,
University of Tuebingen, Tuebingen, Germany.

Purpose: Ocular growth is regulated locally by signals produced in the retina.
As the highly heterogeneous nature of the retina may mask important changes in
gene expression during global analysis, this study focused on changes in gene
expression specifically within the amacrine cell layer (ACL), the most likely
generator of growth signals, during optical manipulation of ocular growth.
Method: Chicks were monocularly treated with either -7D (n=6) or +7D (n=6)
lenses for 24hrs. Untreated age-matched chicks served as controls (n=6). Total
RNA from the ACL was isolated from 10microm thick sections, obtained using laser
capture microdissection. Labelled cRNA was prepared from three samples per
condition and hybridized to Affymetrix GeneChip Chicken Genome arrays. Changes
in gene expression were validated using semi-quantitative real-time RT-PCR.
Results: 128 genes were differentially expressed in the ACL of
minus-lens-treated chicks, while plus-lens-treated eyes displayed 58 changes,
24hrs after treatment. The differential expression of glial-cell-line-derived
neurotrophic factor family receptor alpha 1 (GFRA1), general transcription
factor IIH, polypeptide 5 (GTF2H5), Rab22a and the hypothetical protein
LOC425969 were validated in plus lens treated eyes. Similarly, the differential
expression of angiopoietin 2 (ANGPT2), D4, zinc and double PHD fingers, family 3
(DPF3), G protein gamma 13 (GNG13), GRFA1, CD180 Toll-like receptor (CD180), the
cDNA clones (ChEST267a2, ChEST49o10) and the hypothetical protein LOC425969 were
validated in minus lens treated eyes. Conclusion: The selective removal of the
ACL enabled the identification of several novel genes which may form part of the
growth regulatory pathways of the eye.

PMID: 20207967  [PubMed - as supplied by publisher]

26: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

The Intraflagellar Transport Protein Ift80 is essential for Photoreceptor
Survival in a Zebrafish Model of Jeune Asphyxiating Thoracic Dystrophy.

Hudak LM, Lunt S, Chang CH, Winkler E, Flammer H, Lindsey M, Perkins B.

Texas A&M University, College Station, United States.

Purpose: Jeune's Asphyxiating Thoracic Dystrophy (JATD) is an autosomal
recessive disorder with symptoms of retinal degeneration, kidney cysts, and
chondrodysplasia and results from mutations in the ift80 gene. This study was
conducted to characterize zebrafish lacking ift80 function for photoreceptor
degeneration and defects in ciliogenesis in order to establish zebrafish as a
vertebrate model for visual dysfunction in JATD and to determine if ift80
interacts genetically with Bardet-Biedl Syndrome (BBS) genes. Methods: Zebrafish
were injected with morpholinos (MOs) targeted to the ift80 gene. Retinas were
analyzed by histology, transmission electron microscopy, and
immunohistochemistry. Ear and kidney cilia were analyzed by whole-mount
immunostaining. Intraflagellar Transport (IFT) particle composition was analyzed
by Western blotting. Genetic interactions were tested by co-injection of MOs
against ift80 and bbs4 or bbs8 followed by in situ hybridization. Results:
Zebrafish lacking ift80 function exhibited defects in photoreceptor outer
segment formation, and photoreceptor death. Staining with opsin antibodies
revealed opsin mislocalization in both rods and cones. Ultrastructural analysis
showed abnormal disk stacking and shortened photoreceptor outer segments. The
kinocilia of the ear and motile cilia in the kidney were shorter and reduced in
number. Western blotting revealed a slight increase in the stability of other
IFT proteins. Co-injection of MOs against ift80 and BBS genes led to
convergent-extension defects. Conclusions: Zebrafish lacking ift80 exhibited
defects characteristic of Jeune's Asphyxiating Thoracic Dystrophy. Because the
developing outer segments degenerated, Ift80 could possibly act as a maintenance
factor for the IFT particle.

PMID: 20207966  [PubMed - as supplied by publisher]

27: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

TIMP 1 neutralizes MMPs activity to inhibit pterygium invasion.

Tsai YY, Chiang CC, Yeh KT, Lee H, Cheng YW.

China Medical University Hospital, Department of Ophthalmology, Taichung,
Taiwan.

Purpose: The migration and invasion of tumor cells correlates with the
interaction between MMP and TIMP. Therefore, the aim of this study was to
determine the role of MMP-9, MMP-10 and TIMPs in pterygium formation and
progression. Methods: MMP-9, MMP-10 and TIMP proteins were studied using
immunohistochemistry on 82 pterygial specimens and 30 normal conjunctivas.
Pterygium epithelial cells (PECs), cultured in a serum-free culture medium, and
siRNA were used to knockdown TIMP gene expression to understand the role of TIMP
in pterygium invasion. Results: Among the 82 pterygial samples, there were 29
specimens (35.4%) positive for MMP-9 expression, 28 positive for MMP-10 (34.1%)
and 59 positive for TIMP1 (72.0%). Staining for MMPs was limited to the
cytoplasm of the epithelial layer. The TIMP staining was detected in the
pterygium epithelium, fibroblasts and corneal epithelium. In the cell model,
cell invasion and migration ability increased in TIMP knockdown PEC cells
compared with the parental control. Conclusion: MMP-9 and MMP-10 may play a role
in pterygium formation and TIMPs may contribute to pterygium invasion
inhibition.

PMID: 20207965  [PubMed - as supplied by publisher]

28: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Relationship of Retinal Vascular Tortuosity with Neuroretinal Rim: The Singapore
Malay Eye Study.

Koh VT, Cheung CY, Zheng Y, Wong TY, Wong WL, Aung T.

Singapore Eye Research Institute, Singapore , Singapore.

Purpose: To describe the association of retinal vascular tortuosity, measured
quantitatively, with neuroretinal rim. Methods: A population-based,
cross-sectional study of Malay persons aged 40-80 years residing in Singapore
was conducted. Retinal vascular tortuosity was quantified using a semi-automated
computer-assisted program from retinal fundus photographs, following a
standardized protocol. Optic disc measurements including disc area, rim area and
rim-to-disc area (RDA) ratio were obtained with a confocal scanning laser
ophthalmoscope (Heidelberg Retinal Tomography II). Results: In analyses
adjusting for age, gender, spherical equivalent and retinal vascular caliber,
reduced arteriolar and venular tortuosity were associated with a decrease in
global RDA ratio (P =0.006 and P= 0.001 respectively). When compared to the
arterioles, retinal venular tortuosity demonstrated a stronger association on
RDA ratio. The temporal-inferior region of the neuroretinal rim was most
strongly associated with retinal vascular tortuosity. Conclusion: Straighter
retinal vessels were significantly associated with thinning neuroretinal rim.
These findings may provide additional insights into geometrical retinal vascular
changes seen in early glaucomatous optic neuropathy.

PMID: 20207964  [PubMed - as supplied by publisher]

29: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Taz-Tead1 Links Cell-Cell Contact to Zeb1 Expression, Proliferation and
Dedifferentiation in Retinal Pigment Epithelial Cells.

Liu Y, Xin Y, Ye F, Wang W, Lu Q, Kaplan HJ, Dean DC.

Louisville, United States.

PURPOSE. The Hippo signaling pathway imposes the cell contact inhibition which
establishes organ size and tissue topology from Drosophila to mammals. This
pathway regulates activity of the Yap and Taz transcription factors, which link
epithelial-mesenchymal transition (EMT) to cell proliferation. Here, we provide
evidence that Taz and its co-activator Tead1 regulate expression of the EMT
transcription factor Zeb1 to control RPE cell proliferation and differentiation.
METHODS. Real time PCR was used to examine mRNA expression during RPE
dedifferentiation in primary cultures of RPE cells and following knockdown of
Yap and Taz by lentivirus shRNA. Immunofluorescence was used to follow
subcellular localization of proteins in cells. Chromatin immunoprecipitation was
used to detect Taz at the Zeb1 promoter in vivo. RESULTS. Zeb1 is overexpressed
during RPE dedifferentiation leading to cell proliferation, EMT and repression
of the RPE specification transcription factor gene Mitf. Taz-TEAD1 translocation
to the nucleus coincides with loss of cell-cell contact and with onset of Zeb1
expression in the nucleus. shRNA knockdown of Taz prevented overexpression of
Zeb1 and in turn it prevented proliferation, repression of Mitf and Mitf target
genes and EMT when RPE cells were placed in primary culture. Taz binds to the
Zeb1 promoter in vivo, suggesting that it directly induces Zeb1 transcription.
CONCLUSION. These results provide evidence of a molecular mechanism linking
cell-cell contact to cell proliferation and dedifferentiation in RPE cells.

PMID: 20207963  [PubMed - as supplied by publisher]

30: Invest Ophthalmol Vis Sci. 2010 Mar 5; [Epub ahead of print] 

Monitoring Vigilance During Perimetry with Pupillography.

Henson DB, Emuh T.

School of Medicine, University of Manchester, Manchester, United Kingdom.

Purpose: To report and present data on a method for monitoring patient vigilance
during a visual field test using pupillometry. Methods: Pupil diameter was
recorded at 60Hz using a VET system (CRS, Cambridge, UK) from 13 patients
attending the glaucoma outpatient clinics at Manchester Royal Eye Hospital.
Patients were instructed to fixate a central target and to press a response
button when they saw a stimulus that was randomly presented either 5 degrees to
the left or right of fixation. A repetitive up/down bracketing strategy was used
(1dB steps, 2 s inter stimulus interval, 10 min duration) at these 2 locations.
Wavelet analysis (Wavelet Toolbox v 4.1, The MathWorks, Mass, USA) was used to
extract a de-noised measure of the pupil diameter and the amplitude of any
pupillary fatigue waves. The relationship between the probability of seeing a
stimulus and these 2 components of the pupil response were investigated.
Results: Good pupil data was obtained from 12 patients, most (8/12) showed a
gradual miosis and periods of pupillary fatigue waves during the recorded
session. Pupillary fatigue waves became more evident with test duration and the
probability of seeing a stimulus was higher when the pupil was dilated (p<0.001)
and the amplitude of the papillary fatigue waves was low (p<0.001). Conclusions:
Pupil miosis and fatigue wave amplitude are related to vigilance in patients
undertaking a perimetric-like test. Pupillography can be used to investigate
vigilance and how this contributes to perimetric variability.

PMID: 20207962  [PubMed - as supplied by publisher]