Aims/hypothesis: The study aimed to evaluate the efficacy of recombinant adenovirus expressing αA-crystallin (Ad-αAc-Gfp) in reducing pericyte loss within retinal vasculature in early diabetes. Methods: Diabetes was induced by streptozotocin injection into C57BL/6 mice. Ad-αAc-Gfp was delivered by intravitreous injection to the right eyes of mice 2 weeks before induction of diabetes. Vascular leakage was determined by fluorescent angiography, Evans Blue leakage assay and leucocyte adhesion test. Production of αA-crystallin was analysed by immunoblotting and double immunostaining and pericyte loss was analysed by pericyte count. Results: Vessel leakage and pericyte loss were observed in the streptozotocin-induced diabetic retina. Decreased abundance of αA-crystallin in retinas 2 and 6 months after the induction of diabetes was confirmed by two-dimensional electrophoretic analysis, immunoblotting and RT-PCR. Double immunofluorescence staining for αA-crystallin and NG2 chondroitin sulphate proteoglycan revealed that αA-crystallin was predominantly produced in the retinal pericyte and that the number of αA-crystallin-producing pericytes decreased in the diabetic retina. Retinal infection with Ad-αAc-Gfp led to decreased pericyte loss and vascular leakage compared with control. Conclusions/interpretation: Intravitreal delivery of Ad-αAc-Gfp protects against vascular leakage in the streptozotocin-induced model of diabetes. This effect is associated with the inhibition of diabetic retinal pericyte loss in early diabetes, suggesting that αA-crystallin has a role in preventing the pathogenesis of early diabetic retinopathy. © 2012 Springer-Verlag.
CITATION STYLE
Kim, Y. H., Park, S. Y., Park, J., Kim, Y. S., Hwang, E. M., Park, J. Y., … Choi, W. S. (2012). Reduction of experimental diabetic vascular leakage and pericyte apoptosis in mice by delivery of αa-crystallin with a recombinant adenovirus. Diabetologia, 55(10), 2835–2844. https://doi.org/10.1007/s00125-012-2625-y
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