Strain-Independent Increases of Crystallin Proteins in the Retina of Type 1 Diabetic Rats

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.

RNA sequencing reveals retinal transcriptome changes in STZ-induced diabetic rats

“…αA- and αB-crystallin, which can protect retinal neurons from cell death ( 46 ), show increased expression in the early stages of the disease and decreased expression as the disease progresses. In the present study, it was found that the expression levels of αA- and αB crystallins were downregulated 12 weeks following STZ induction, and the inconsistency in these findings with those of other reports ( 47 – 49 ) may be due to different durations of hyperglycemia, different species and/or different strains of animals. The expression of crystallins is a dynamic process that is associated with the duration of hyperglycemia and the extent of the pathogenic condition ( 47 , 50 ).…”

Methylglyoxal induces retinopathy‐type lesions in the absence of hyperglycemia: studies in a rat model

“…A recent study demonstrated that up-regulation of crystallins in the retina is consistent across different rat models of diabetes. Indeed, similar expression patterns were observed after 4 wk of both diabetes and MG exposure, with concordant induction of aA, aB, bA2, bA4, bB2, gC, and gD crystallins (45). Retinal cells express transcripts for 20 different members of the crystallin gene family.…”

A specific phosphorylation regulates the protective role of αA-crystallin in diabetes

“…PTMs and their consequences on the chaperone function of α-crystallins have been only minimally studied outside of the lens. We and others previously demonstrated a correlation between levels of expression and phosphorylation on serine residues 19, 45, and 59 of αB-crystallin in the retina in response to diabetes (21,26). Serine residue 148 in rodents and threonine 148 in humans have been previously reported as phosphorylation sites of lenticular αA-crystallin (30) as well as in brain astrocytes in culture (31).…”

“…Such changes are associated with decreased chaperone activity and protective capacity of αB-crystallin, in part due to posttranslational modifications (PTMs) (20), such as its phosphorylation (21). However the nature and impact of αA-crystallin PTM remains poorly understood.…”