Reduction of experimental diabetic vascular leakage and pericyte apoptosis in mice by delivery of αa-crystallin with a recombinant adenovirus

Y. H. Kim, S. Y. Park, J. Park, Y. S. Kim, E. M. Hwang, J. Y. Park, G. S. Roh, H. J. Kim, S. S. Kang, G. J. Cho, W. S. Choi

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19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2835-2844
Number of pages10
JournalDiabetologia
Volume55
Issue number10
DOIs
Publication statusPublished - 2012 Oct 1

Keywords

  • BRB breakdown
  • Diabetic retinopathy
  • Pericyte loss
  • αA-Crystallin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Kim, Y. H., Park, S. Y., Park, J., Kim, Y. S., Hwang, E. M., Park, J. Y., Roh, G. S., Kim, H. J., Kang, S. S., Cho, G. J., & 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