(485bk) Reversing Retinal Cell Death in Diabetic Rats' with Subconjunctivally Implanted Hydrogels

Diabetic retinopathy involves retinal neuronal cell loss which leads to vision loss. Intensive metabolic control with systemic insulin therapy reduces the risk of diabetic retinopathy, but it may induce hypoglycemia. Our group has been developing novel hydrogels consisting of thermoresponsive and hydrolytically degradable properties for long-term release of low dose insulin to the retina toretard the development and progression of early diabetic retinopathy. The hydrogels were formulated by synthesizing in dimethyl formamide medium under UV irradiation. FITC-labeled insulin or Humalog was loaded during the process of hydrogel synthesis. The hydrogels released FITC-labeled insulin in phosphate buffered saline, PBS, at 37 °C for more than 5 months and composition of the hydrogels and their formulation strategies regulated the release of inulsin. Hydrogels did not show any adverse inflammatory effects for 2 months after subconjunctival implantation to rats. The implanted hydrogels released both FITC-labeled insulin and Humalog, which were detected by confocal microscopy and Humalong-specific radioimmunoassay, respectively. Ex-vivo retinal cultures confirmed that insulin released from hydrogels was bio-active. Humalog-loaded hydrogels decreased DNA fragmentation, caused due to cell death, in the retina of diabetic rats after subconjunctival implantation suggesting that the hydrogels have potential to reverse the symptoms of diabetic retinopathy.