Abstract

Diabetic retinopathy is the leading cause of vision loss in working-age individuals in the United States and is expected to continue growing with the increased prevalence of diabetes. Streptozotocin-induced hyperglycemia in rats is the most commonly used model for diabetic retinopathy. Previous studies have shown that this model can lead to different inflammatory changes in the retina depending on the strain of rat. Our previous work has shown that crystallin proteins, including members of the alpha- and beta/gamma-crystallin subfamilies, are upregulated in the STZ rat retina. Crystallin proteins have been implicated in a number of cellular processes, such as neuroprotection, non-native protein folding and vascular remodeling. In this current study, we have demonstrated that unlike other strain-dependent changes, such as inflammatory cytokines and growth factor levels, in the STZ rat, the protein upregulation of crystallins is consistent across the Brown Norway, Long-Evans and Sprague-Dawley rat strains in the context of diabetes. Taken together, these data illustrate the potential critical role played by crystallins, and especially alpha-crystallins, in the retina in the context of diabetes.

Highlights

  • Diabetes mellitus is a growing health concern as well as economic burden worldwide, especially due to the difficult management of its associated complications

  • At 4 weeks, a slight increase in alphaA- and alphaB-crystallin mRNA levels was observed in the diabetic rats of the SD and Brown Norway (BN) strains compared to the mRNA levels of their control littermates

  • While profiles of transcription of all crystallin proteins were similar in all three strains tested, beta-crystallin transcripts were only affected by 12 weeks of diabetes in BN rats (Figure 2)

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Summary

Introduction

Diabetes mellitus is a growing health concern as well as economic burden worldwide, especially due to the difficult management of its associated complications. Numerous studies have demonstrated commonalities between this animal model and the human pathology, including neuronal cell loss, glial cell activation, increased vascular permeability and inflammation [2,3,4,5,6,7]. It has been shown, that different rat strains exhibit different responses to hyperglycemia and other insults to the retina [8,9,10]. This study was the first to demonstrate that some of the effects observed or associated with diabetes were strain dependent

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