Date of this Version
Purpose: A sustained gene modulatory strategy is necessary for regulating abnormal gene expression in diabetic retinopathy, a long-term complication. We investigated the efficacy of a small interference RNA (siRNA) strategy in mediating the long-term downregulatory effect of fibronectin (FN) overexpression in vivo.
Methods: Streptozotocin-induced diabetic rats were intravitreally injected with 3 µM of FN-siRNA at six week intervals over a period of 4.5 months. Retinal FN protein expression, vascular basement membrane (BM) thickness, and retinal vascular cell loss were assessed by western blot, electron microscopy, and retinal trypsin digest, respectively.
Results: Retinal FN expression and BM thickness were significantly increased in diabetic rat retinas compared to those in non-diabetic control rats (188±14.2% of control versus 100±7.4% of control, p
Conclusions: These findings suggest that BM thickening is an important target for preventing vascular cell loss in a diabetic retina, and that the siRNA approach could be useful for long-term gene modulation in diabetic retinopathy.
This article is published under a Creative Commons Attribution-NonCommercial-NoDerivatives License 3.0, or CC BY-NC-ND 3.0 (see http://creativecommons.org/licenses/by-nc-nd/3.0/ for license terms).
Animals, Basement Membrane, Blood Glucose, Body Weight, Capillaries, Diabetic Retinopathy, Fibronectins, Hemoglobin A, Glycosylated, Intravitreal Injections, Male, Pericytes, RNA, Small Interfering, Rats, Sprague-Dawley, Retina, Time Factors
Roy, S., Nasser, S., Graves, D. T., & Roy, S. (2011). A Long-Term siRNA Strategy Regulates Fibronectin Overexpression and Improves Vascular Lesions in Retinas of Diabetic Rats. Molecular Vision, 17 3166-3174. Retrieved from https://repository.upenn.edu/dental_papers/28
Date Posted: 02 April 2015
This document has been peer reviewed.