Retinal blood vessel-origin yes-associated protein (YAP) governs astrocytic maturation via leukaemia inhibitory factor (LIF).

OBJECTIVES: To testify that endothelial cells (ECs) induce astrocyte maturation by leukaemia inhibitory factor (LIF) secretion. MATERIALS AND METHODS: In vivo experiments, mice bearing floxed alleles of YAP were crossed with mice expressing a Cre recombinase driven by the endothelial Tek promoter (Tek-Cre) to finally obtain the following three genotypes: YAPf/f , Tek-Cre; YAPf/w , Tek-Cre; and YAPf/f . Retinal vascularization and astrocyte network were evaluated by whole-mount fluorescence and Western blotting. In vitro, experiments were performed in an astrocyte and human microvascular endothelial cell (HMEC-1) coculture model to analyse the mechanisms underlying the effect of endothelial YAP on astrocytes. RESULTS: In vivo, YAPf/f ;Tek-Cre mice showed delayed angiogenesis, sparse vessels and decreased glial fibrillary acidic protein (GFAP)+ astrocytes but aberrant growth of endothelial networks and immature astrocytes (platelet-derived growth factor A, PDGFRA+ astrocytes) overgrowth. In vitro, Yap deletion attenuated the LIF release that delayed the maturation of retinal astrocyte which was consistent with the results of HMEC-1-astrocyte coculture. The effect of YAP overexpression on LIF-LIFR axis in HMEC-1 interferes the GFAP expression of astrocyte. In contrast, LIF protein rescues the astrocytic GFAP expression when EC YAP was inhibited by siRNAs. CONCLUSIONS: We show that EC yes-associated protein (YAP) is not only a critical coactivator of Hippo signalling in retinal vessel development but also plays an essential role in retinal astrocyte maturation by regulating LIF production.

The link between apolipoprotein E, presenilin 1, and kinesin light chain 1 gene polymorphisms and age-related cortical cataracts in the Chinese population.

PURPOSE: To study whether presenilin 1 (PSEN1), apolipoprotein E (APOE), and kinesin light chain 1 (KLC1) genotypes are associated with the risk of developing age-related cortical cataracts in the Han Chinese population. METHODS: We collected and analyzed the blood samples of 227 cortical cataract patients and 263 controls. Genotyping was performed by direct sequencing after PCR amplification, and allele frequencies were tested for the Hardy-Weinberg equilibrium. RESULTS: The G allele and GG genotype of KLC1 rs8702 were significantly over-represented among cataract patients, as compared to healthy controls (allele P[χ2]=0.001 and genotype P[χ2]=0.008, respectively) and are associated with an odds ratio for cataract development of 1.54 (95% confidence interval of 1.19-2.01). More specifically, carrying the rs8702 C allele was associated with a decreased cortical cataract risk among individuals devoid of the APOE4 allele (OR=0.55; P[χ2]=0.003), whereas it has no significant effect among APOE4 carriers (OR=0.57; P[χ2]=0.36). CONCLUSIONS: The KLC1 and APOE genes may be novel susceptibility genes for age-related cataracts.

Amino-Nogo inhibits optic nerve regeneration and functional recovery via the integrin αv signaling pathway in rats.

BACKGROUND: Nogo-A, a major myelin-associated inhibitor, can inhibit injured optic nerve regeneration. However, whether Amino-Nogo is the most important functional domain of Nogo-A remains unknown. This study aimed to identify the role of Amino-Nogo following optic nerve injury, and the mechanism of the Amino-Nogo-integrin αv signaling pathway in vivo. METHODS: Sprague-Dawley rats with optic nerve crush injury were injected with Nogo-A siRNA (Nogo-A-siRNA), the Nogo-66 functional domain antagonist peptide of Nogo-A (Nep1-40) or a recombinant rat Amino-Nogo-A protein (∆20) into the vitreous cavity to knock down Nogo-A, inhibit Nogo-66 or activate the Amino-Nogo, resparately. Retinal ganglion cell (RGC) density, axon regeneration and the pattern of NPN of visual electrophysiology (flash visual evoked potentials [F-VEP]) at different times post-injury were investigated. RESULTS: Our study revealed a lower RGC survival rate; shorter axonal outgrowth; longer N1, P1 and N2 waves latencies; and lower N1-P1 and P1-N2 amplitudes in the Δ20 group, and Δ20 treatment significantly attenuated integrin αv expression and phosphorylated focal adhesion kinase (p-FAK) levels. In the Nep1-40 and Nogo-A siRNA groups, there were higher RGC survival rates, longer axonal outgrowth, shorter N1 and P1 wave latencies, and higher N1-P1 and P1-N2amplitudes. Nogo-A siRNA treatment significantly increased integrin αv expression and p-FAK levels. Nepl-40 treatment did not alter integrin αv expression. In addition, there was no significant change in integrin α5 in any group. CONCLUSION: These results suggest that the integrin signaling pathway is regulated by Amino-Nogo, which inhibits optic nerve regeneration and functional recovery, and that the integrin subunit involved might be integrin αv but not integrin α5.

Inhibition of retinal ganglion cell axonal outgrowth through the Amino-Nogo-A signaling pathway.

Nogo-A is a myelin-derived inhibitor playing a pivotal role in the prevention of axonal regeneration. A functional domain of Nogo-A, Amino-Nogo, exerts an inhibitory effect on axonal regeneration, although the mechanism is unclear. The present study investigated the role of the Amino-Nogo-integrin signaling pathway in primary retinal ganglion cells (RGCs) with respect to axonal outgrowth, which is required for axonal regeneration. Immunohistochemistry showed that integrin αv, integrin α5 and FAK were widely expressed in the visual system. Thy-1 and GAP-43 immunofluorescence showed that axonal outgrowth of RGCs was promoted by Nogo-A siRNA and a peptide antagonist of the Nogo-66 functional domain of Nogo-A (Nep1-40), and inhibited by a recombinant rat Nogo-A-Fc chimeric protein (Δ20). Western blotting revealed increased integrin αv and p-FAK expression in Nogo-A siRNA group, decreased integrin αv expression in Δ20 group and decreased p-FAK expression in Nep1-40 group. Integrin α5 expression was not changed in any group. RhoA G-LISA showed that RhoA activation was inhibited by Nogo-A siRNA and Δ20, but increased by Nep1-40 treatment. These results suggest that Amino-Nogo inhibits RGC axonal outgrowth primarily through the integrin αv signaling pathway.

Association between MTHFR C677T polymorphism and primary open-angle glaucoma: a meta-analysis.

Epidemiological studies have evaluated the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and primary open-angle glaucoma (POAG) risk. However, the results remain conflicting. The aim of this study was to investigate the association between MTHFRC677T polymorphism and POAG risk. All genetic association studies on MTHFR C677T polymorphism and POAG were systematically searched by the electronic databases PubMed, Embase and Web of Science. Study selection, data abstraction and study quality evaluation were conducted in duplicate independently. The strength of association between MTHFR C677T polymorphism and POAG was measured by odds ratios (ORs) and 95% confidence intervals (CIs). Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 10 studies including 1224 cases and 1105 controls were included in our final meta-analysis. There was no evidence of significant association of the overall population (for allelic model: OR=1.17, 95% CI=0.94-1.46; for additive model: OR=1.15, 95% CI=0.85-1.57; for dominant model: OR=1.19, 95% CI=0.92-1.55 and for recessive model: OR=1.11, 95% CI=0.83-1.49). Significant associations were found between MTHFR C677T polymorphisms and POAG in allelic model (OR=1.39, 95% CI=1.05-1.83) and additive model (OR=1.88, 95% CI=1.04-3.43) for population-based (PB) subgroup. This meta-analysis suggested that there were significant associations between MTHFR C677T polymorphism and POAG in allelic model and additive model for PB subgroup which indicated that the T allele or TT genotype might increase the risk of POAG, whereas no evidence of significant association was shown of the overall studied population. However, this conclusion should be interpreted cautiously. More large sample-size and multi-ethnicity studies with well-defined POAG patients and well-study design are needed in the future study.

Clinical features of ankylosing spondylitis associated with acute anterior uveitis in Chinese patients.

AIM: To characterize the clinical features, diagnosis, treatment and prognosis of uveitis associated with ankylosing spondylitis (AS) in Chinese patients. METHODS: Two hundred and three patients with uveitis associated with AS followed-up in the Third Military Medical University Daping Hospital between 2005 and 2010 were retrospectively evaluated in this study. Complete ophthalmological examinations were evaluated at baseline and during the follow-up period. The gender, age, follow-up time, mean frequency of uveitis onset, and accompanying eye examination findings, history, demographical parameters were reviewed. All the patients presented complete clinical and radiologic (sacroiliac, lumbar, dorsal and cervical spine, knee, ankle, shoulder, hip, elbow) evaluation. HLA-B27 typing was also searched. RESULTS: There were 203 patients diagnosed with AS associated uveitis. All showed sacroiliac X-ray changes indicative of AS. There were 184 male and 19 female patients. The average age of patients was 35±12 (range 18-50). Mean follow-up period was 2.4 years (1-5 years). Acute anterior uveitis was the most common type of uveitis in both genders. 121 eyes presented unilateral involvement (55.2%), and 92 eyes presented bilateral involvement (45.3%) with onset alternately. 22 eyes occurred hypopyon, 16 eyes were found anterior vitreous cells, 7 eyes were noted reactive macular edema or exudation, 29 eyes presented posterior synechiae of iris, and 14 eyes presented cataract, 9 eyes presented secondary glaucoma, 2 eyes presented bend corneal degeneration and 1 eyes presented atrophy of eyeball. At the final visit, uveitis was well controlled in most patients. CONCLUSION: AS associated with uveitis in Chinese patients mainly manifests as acute anterior uveitis. A combination of corticosteroids with other mydriasis agents is effective for most AS associated with uveitis patients. In general, the prognosis is good in these cases.

[Expression of Nogo-A and Nogo receptor in neonatal rats visual system during development].

OBJECTIVE: To study the expression of Nogo-A and Nogo receptor (NgR) in the development of neonatal rats retinal and visual cortex and their effects on the development of central nervous system (CNS). METHODS: Immunohistochemical staining method was used to detect the expression of Nogo-A and NgR in neonatal rats retinal and visual cortex at 1, 3, 7, 14, 28, 56 days after birth. One-way Anova was used to analyze the results of Western blot analysis of Nogo-A and NgR in neonatal rats visual cortex. RESULTS: Nogo-A and NgR was found to express in neonatal rats retinal and visual cortex at the developing stage. In 1, 3, 7, 14, 28, 56 days, the IDV ratio of Nogo-A was 0.852 ± 0.026, 0.917 ± 0.024, 0.810 ± 0.028, 0.417 ± 0.053, 0.258 ± 0.029, 0.298 ± 0.054 respectively and the IDV ratio of NgR was 0.070 ± 0.014, 0.185 ± 0.035, 0.678 ± 0.046, 0.705 ± 0.021, 1.210 ± 0.057, 1.140 ± 0.0420 respectively by Western blot analysis. The expression of Nogo-A was decreased (F = 376.56, P = 0.000) and the expression of NgR was increased (F = 888.26, P = 0.000) during postnatal development. CONCLUSION: Nogo-A and NgR is closely related to the CNS growth and development.

A case of circumscribed choroidal hemangioma in Sturge-Weber syndrome in China.

We present a case of circumscribed choroidal hemangioma (CCH) in Sturge-Weber syndrome in a 30-year-old woman with congenital port-wine stains on the left side of face involving the upper eyelid, cheek and the nose, and she had undergone facial hemangioma surgery 3 years ago suggestive of Sturge-Weber syndrome. She presented with a 1-month history of rapidly decreased visual acuity (VA) to counting fingers in the left eye which had no prior history of visual problem. And there was no evidence of glaucoma. At 3 months after the treatment of the standard photodynamic therapy (PDT) the VA was 20/200. For some reasons, we have no idea about the changes of tumor thickness and subretinal fluid. We confirmed the curative effect of PDT treatment for CCH because of the significantly improved VA in the bad eye.

Bietti crystalline dystrophy with bilateral macular holes.

OBJECTIVE: Bietti crystalline dystrophy is a rare form of tapetoretinal degeneration associated with retinal crystalline deposits. However, Bietti crystalline dystrophy is extremely unusually associated with macular hole formation. A 32-year-old man with Bietti crystalline dystrophy and bilateral macular holes is described. DESIGN: Case report and literature review. RESULTS: Clinical and angiographic features, optical coherence tomography results, electroretinographic findings, and visual evoked potentials are reported. CONCLUSION: Bietti crystalline dystrophy can occur with bilateral macular holes, but the cause is unclear.