Diabetic eNOS Knockout Mice Develop Accelerated Retinopathy

Abstract

Purpose: : Dysfunction of endothelial nitric oxide synthase (eNOS) has been implicated in pathogenesis of diabetic vascular complications in recent studies, we aimed to determine the role of eNOS in the development of DR by investigating the functional consequence of its deficiency in the diabetic state.

Results: : Diabetic eNOS-/- mice exhibit more severe retinal vascular permeability, detectable as early as 3 weeks after induced diabetes comparing to age-matched diabetic C57B/6 mice. Diabetic eNOS-/- mice also show increased leukocytes adhesion, earlier onset and increased number of acellular capillaries. Proliferating retinal endothelial cells can be detected 3 month after induced diabetes, increased rapidly after 5 month, whereas they were not detectable in C57B/6 mice at all stages of diabetes studied (up to 13 month after induced diabetes).

Conclusions: : These results show that diabetic eNOS-/- mice exhibit significantly wider range of severe retinal vascular complications than age-matched diabetic C57B/6 mice, supporting the notion that eNOS- derived NO plays an essential role in retinal vascular function. This mouse model also better resembles the vascular changes associated human disease, thus provides a good model to further study the pathologic mechanism and to develop effective therapeutic strategies.

Keywords: diabetic retinopathy • diabetes • nitric oxide