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M Nour, K Alvarez, A Quiambao, WM Peterson, MR Al-Ubaidi, MI Naash; Effects of P2Y2 Receptor Agonist (INS37217) on Recovery of Retinal Morpohology and Function Following Subretinal Injections in Mice: Potential Use in Gene Therapy Delivery . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4610.
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Purpose: To evaluate the effects of P2Y2 receptor agonist, INS37217, on recovery of retinal morphology and electroretinography (ERG) following subretinal therapeutic delivery of viral vectors in mice. INS37217 has previously been shown to enhance subretinal fluid reabsorption in experimental models of retinal detachment. Methods: Subretinal injections of 1µl of fluorescent micro-beads, saline, or INS37217 (100µM) were made using the intra-corneal method in C57BL/6 mice. Control, mock-injected animals underwent corneal puncture without subretinal injection. Histological and ERG evaluations were made at 0-1 hr, 8 hr, 24 hr, 3 days, 7 days, 14 days and 2 months post-injection (PI). Results: Fluorescent images show a distribution of micro-beads to ∼ 90% of the subretinal space following a single injection. An extensive retinal detachment was visible immediately after each subretinal injection and morphological reattachment was evident by 24 hr PI. Relative to mock-injected controls, at 24 hr PI, saline-injected animals showed a 40% recovery of dark-adapted a- and b-wave amplitudes. Gradual recovery of the rod response was evident at later time points, reaching 90% at 2 months PI. Preliminary data indicates that INS37217 delivery to the subretinal space contributes to an additional 30% functional improvement, first seen at 24 hr PI. Studies are currently underway to evaluate the effects of INS37217 in the recovery of retinal function following subretinal injection of AAV viral vectors. Conclusions: While morphological reattachment of the retina is apparent as early as 24 hr post-injection, our results demonstrate that ERG recovery remains significantly delayed. Current data suggests a potential role for P2Y2 agonist, INS37217, in enhancing the rate of ERG recovery following subretinal injections.
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