dinoprost and Retinal-Degeneration

Green tea extracts exhibit anti-oxidative and anti-inflammatory actions in different disease conditions. We hypothesized that green tea extract and its catechin constituents ameliorate sodium iodate-induced retinal degeneration in rats by counteracting oxidative stress. In this study, adult Sprague-Dawley rats were intravenously injected with a single dose of sodium iodate. Green tea extract (GTE; Theaphenon-E) or combinations of its catechin constituents, including (-)-epigallocatechin gallate (EGCG), were administered intra-gastrically before injection. Live imaging analysis using confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography showed a progressive increase of degenerating profile across the retinal surface and decrease in thickness of outer nuclear layer (ONL) at Day-14 of post-injection. These lesions were significantly ameliorated by Theaphenon-E and catechin combinations with EGCG. Catechins with exclusion of EGCG did not show obvious protective effect. Histological analyses confirmed that Theaphenon-E and catechins containing EGCG protect the retina by reducing ONL disruption. Retinal protective effects were associated with reduced expression of superoxide dismutase, glutathione peroxidase and caspase-3, and suppression of 8-iso-Prostaglandin F2α generation in the retina. In summary, GTE and its catechin constituents are potent anti-oxidants that offer neuroprotection to the outer retinal degeneration after sodium iodate insult, among which EGCG is the most active constituent.

Topics: Administration, Oral; Animals; Antioxidants; Catechin; Dinoprost; Gene Expression Regulation; Iodates; Ophthalmoscopy; Oxidative Stress; Rats, Sprague-Dawley; Retinal Degeneration; Retinal Pigment Epithelium; Tea

To evaluate the long-term protective effects of transscleral unoprostone (UNO) against retinal degeneration in transgenic (Tg) rabbits (Pro347Leu rhodopsin mutation).. The UNO release devices (URDs) were implanted into the sclerae of Tg rabbits and ERG, optical coherence tomography (OCT), and ophthalmic examinations were conducted for 40 weeks. Unoprostone metabolites in retina, choroid/RPE, aqueous humor, and plasma from wild-type (Wt) rabbits were measured using liquid chromatography-tandem mass spectrometry. In situ hybridization and immunohistochemistry evaluated the retinal distribution of big potassium (BK) channels, and RT-PCR evaluated the expressions of BK channels and m-opsin at 1 week after URD treatment.. The URD released UNO at a rate of 10.2 ±1.0 μg/d, and the release rate and amount of UNO decreased during 32 weeks. Higher ERG amplitudes were observed in the URD-treated Tg rabbits compared with the placebo-URD, or nontreated controls. At 24 weeks after implantation into the URD-treated Tg rabbits, OCT images showed preservation of retinal thickness, and histologic examinations (44 weeks) showed greater thickness of outer nuclear layers. Unoprostone was detected in the retina, choroid, and plasma of Wt rabbits. Retina/plasma ratio of UNO levels were 38.0 vs. 0.68 ng UNO*hour/mL in the URD-treated group versus control (topical UNO), respectively. Big potassium channels were observed in cone, cone ON-bipolar, and rod bipolar cells. Reverse-transcriptase PCR demonstrated BK channels and m-opsins increased in URD-treated eyes.. In Tg rabbits, URD use slowed the decline of retinal function for more than 32 weeks, and therefore provides a promising tool for long-term treatment of RP.

Topics: Animals; Animals, Genetically Modified; Aqueous Humor; Choroid; Chromatography, Liquid; Delayed-Action Preparations; Dinoprost; Disease Models, Animal; DNA; DNA Mutational Analysis; Drug Implants; Electroretinography; Follow-Up Studies; Gene Expression Regulation; Immunohistochemistry; In Situ Hybridization; Large-Conductance Calcium-Activated Potassium Channels; Mutation; Rabbits; Retina; Retinal Degeneration; Reverse Transcriptase Polymerase Chain Reaction; Rhodopsin; Sclera; Time Factors; Tomography, Optical Coherence