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Ruth E. Rosenstein, Pablo H. Sande, Mónica S. Chianelli, Hernán J. Aldana Marcos, Diego C. Fernandez; Induction Of Ischemic Tolerance Protects he The Retina From Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5957.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) is a leading cause of acquired blindness. Available treatments are not very effective. We investigated the effect of a weekly application of brief retinal ischemia pulses (ischemic conditioning) on retinal damage induced by experimental diabetes.
Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ). Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 min; this maneuver started 3 days after STZ injection and was weekly repeated in one eye while the contralateral eye was submitted to a sham procedure. DR was evaluated in terms of: i) retinal function (electroretinogram (ERG) and oscillatory potentials (OPs)), ii) integrity of blood- retinal barrier (by albumin-Evan's Blue complex leakage and astrocyte glial fibrillary acidic protein (GFAP) immunohistochemistry) iii) optical and electron microscopy histopathological studies, and iv) vascular endothelial growth factor (VEGF) levels (by Western blot and immunohistochemistry).
Brief ischemia pulses significantly preserved ERG a- and b-wave and OPs, avoided albumin-Evan's blue leakage, prevented the decrease in astrocyte GFAP levels, and reduced the appearance of retinal edemas in diabetic rats. Ischemia pulses prevented the increase in VEGF levels induced by experimental diabetes. When the application of ischemia pulses started 6 weeks after diabetes onset, retinal function was significantly preserved.
These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies in DR treatment.
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