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Direct exposure to Ultraviolet (UV) radiation causes progressive damages in retinal cells, which is one of the hypothetical mechanisms underlying age-related retinopathy or macular degeneration. The protective effects of Apocynin against UV damages were firstly tested in retinal pigment epithelium cells (RPEs) and retinal ganglion cells (RGCs). Subsequently the beneficial effect of Apocynin on mouse retinas against light damage were examined. Next, microarray profiling was used to identify the genes regulated by Apocynin in both RPEs and RGCs. A candidate gene was isolated for functional characterisation by knock-down study. Apocynin was shown to inhibit cell death, reduce oxidative stress and deoxyribonucleic acid damages in both RPEs and RGCs challenged with UV. Intravitreal application of Apocynin also improved retinal dysfunction caused by light damage. Sirtuin 1 (SIRT1) was identified as induced by Apocynin by microarray study. The induction was confirmed by realtime-PCR and western blotting. Knocking down SIRT1 antagonised the protective effect of Apocynin against UV damages in both RPEs and RGCs. Apocynin is a novel agent that shows both in vitro and in vivo efficacies against UV radiation induced retina damages. SIRT1 pathway is implicated in UV radiation protection of Apocynin in retinal cells. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the role played by platelet-derived growth factor-αα (PDGFRαα) in oxidative stress-induced retinal cell death. A previous proteomic study from our laboratory showed that expression of PDGFRαα is elevated considerably in the retinas of an animal model of glaucoma--the excitatory amino acid carrier (EAAC) 1-deficient (EAAC1-/-) mouse. Methods: Retinal sites and expression patterns of PDGFRαα were determined by immunohistochemistry in the retinas of EAAC1-/- and control CRL:CD1(ICR) mice. A retinal cell line was exposed to hydrogen peroxide, and expression PDGFRαα determined by Western blot analysis. Effects of PDGF-AA and PDGFRαα-siRNA on hydrogen peroxide-induced retinal cell death were examined. Results: PDGFRαα was detected in the retinal ganglion cell layer (RGL) of both EAAC1-/- and ICR mice, and was also localized in the internal nuclear layer (INL) of EAAC1-/- mice. While treatment with excess PDGF-AA had no additional effect on retinal cell death, expression of PDGFRαα increased with exposure to hydrogen peroxide. Hydrogen peroxide-induced retinal cell death was inhibited by exposure to PDGF-AA via phosphatidylinositol 3 kinase (PI3K); cell death was promoted by PDGFRαα-siRNA. Conclusions: PDGFRαα is expressed in mouse retina, where it is essential for retinal cell survival under conditions of oxidative stress. [ABSTRACT FROM AUTHOR]

Purpose: Alkylphosphocholines (APCs) are investigated for their effect on Müller glial cell proliferation and F-actin stress fiber distribution in vitro. Materials and Methods: Müller cells were incubated with APCs (C18:1-PC and C22:1-PC) ± fetal calf serum. Proliferation was assessed by BrdU labeling and with the tetrazolium dye-reduction assay. Toxicity was measured using the trypan blue exclusion assay. The distribution of F-actin stress fibers was determined using FITC-phalloidin staining. Results: APCs are effective inhibitors of human and rat Müller glial cell proliferation and hypoxia-induced up-regulation of F-actin stress fibers in vitro in non-toxic concentrations. Conclusions: APCs might prevent intraretinal changes as a result of serum stimulation and hypoxia following retinal detachment. [ABSTRACT FROM AUTHOR]

Purpose : To investigate the effect of intraocular erucylphosphocholine (ErPC) on the retina, the retinal pigment epithelium (RPE), and the choroid in an in vivo rat model. Methods : Adult male Brown Norway rats were injected intravitreally with ErPC dissolved in balanced salt solution (BSS) at a final concentration of 10 or 100 μ M with BSS serving as control. Adverse effects on the anterior and posterior segment were assessed by slit-lamp biomicroscopy and ophthalmoscopy. Retinal toxicity was assessed by electroretinography (ERG), retinal ganglion cell (RGC) quantification, and histology 7 days after intravitreal administration of ErPC. Results : There was neither a statistically significant difference in the clinical examination nor in the ERG waves of treated versus control rats 7 days after intravitreal administration of ErPC. Correspondingly, the number of RGC after BSS injection did not differ significantly from ErPC-injected animals. Histologic sections of the posterior segment of 10 and 100 μ M ErPC-injected rats did not show any signs of retinal toxicity. Electron microscopy did not display a difference between the 10 μM and the control group. Only the 100 μM-injected animals showed a discrete irregularity of the Müller cell and the retinal ganglion cell cytoplasm at the ultrastructural level. Conclusions : ErPC can safely be injected into the vitreous of adult rats at a concentration of 10 μM without any retinal toxicity. Even a 10-fold increase in ErPC concentration leads only to a discrete cytoplasmic irregularity of the innermost retinal layers. [ABSTRACT FROM AUTHOR]