Ocular findings in Zucker Diabetic Fatty rats emphasize the key role of neuroglia degeneration in diabetic retinopathy pathophysiology

Abstract

Diabetes mellitus is a leading cause of acquired vision loss and one of the world's fastest growing chronic diseases. Diabetic retinopathy (DR), a specific complication of chronic hyperglycemia, is the leading cause of acquired vision loss worldwide in middle-aged and therefore economically active people that also increases the medical and economic burden on the society (Klein, 2007). The natural history of DR has been divided into two clinical stages based on the proliferative status of the retinal vasculature: an early, non-proliferative stage and an advanced, proliferative or neovascular stage. Although DR has been regarded as a vascular disorder for many years, neuroglial abnormalities have also been recognized and are still being explored to determine their clinical significance. A lot of important information or clues on the development of DR can be obtained from human studies; however, the complete mechanisms of DR development have not yet been elucidated. In this sense, diabetic rat models are playing key roles in elucidating the pathogenesis of human diabetes and its complications, such as nephropathy, retinopathy, and neuropathy. Although spontaneous diabetic rat models are well characterized in terms of retina-choroid vascular modifications, changes in retinal cells (neurons and glia) associated with hyperglycemia have not been studied in detail on most available models (Lai and Lo, 2013; Olivares et al., 2017). Early structural gliotic reactions were initially described in pharmacologically induced rat models of diabetes (Rungger-Brändle et al., 2000). Recently, neuroglial morphologic degenerative changes have been described in spontaneous diabetic Zucker Diabetic Fatty (ZDF) rats prior to changes in vasculature appearance (Fernandez-Bueno et al., 2017). The ocular findings observed in animal models of diabetes, such as the ZDF rats, emphasize that DR is not, at least initially, a primary vascular disorder and that prolonged damage to the neural and glial components of the retina plays a key role in the development of the disease. [Texto extraído introducción]