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Claire Allen, Jacqueline L Whatmore, Mark E Wood, Matthew Whiteman, David O Bates; Hydrogen sulfide as a novel therapeutic for diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4043.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of blindness worldwide. Current treatments for DR are limited, expensive and non-specific. The anti-inflammatory gaseous transmitter hydrogen sulfide (H2S) is significantly reduced in type 2 diabetic patients and correlates with microvascular dysfunction. H2S is thought to contribute to the healthy functioning of the microvasculature by preventing loss of the retinal endothelial glycocalyx and subsequent breakdown of the blood retinal barrier.
Fundus Fluorescein Angiography (FFA) was performed in isofluorane anaesthetised Norway Brown rats on day 0 and 7 using the Micron IV retinal imaging microscope (Phoenix Research Labs). Animals received an intraocular injection of the slow release H2S donor sodium 4-methoxyphenyl(morpholino)-phosphinodithioate (NaGYY4137; 1µM) on day 0 (Prevention) or on day 6 (Treatment). On day 1 some animals received a single dose of streptozotocin (50mg/kg, i.p.) to induce diabetes and blood glucose levels measured. Angiograms were imported into ImageJ software and fluorescence was measured in the interstitium and vessel. The ratio of interstitial to vascular fluorescence was adjusted for background and plotted against time and the slope used to determine an estimate of permeability.
NaGYY4137 significantly (p <0.05) reduced retinal permeability in non- and diabetic rats on day 7 when given as a single intraocular preventative dose on day 0. In addition NaGYY4137 significantly reduced (p <0.05) retinal permeability in non-diabetic rats when administered therapeutically (day 6) and stabilised retinal permeability in rats with pre-existing diabetes. This was further supported by fundus images showing increased capillary leakage and microaneurysm formation in the retina of diabetic animals.
NaGYY4137 protected the retinal endothelial permeability barrier from diabetes-associated loss of integrity and reduced the progression of DR. Slow release H2S donors may therefore be a potential alternative and more specific therapeutic candidate for DR.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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