Impact of diabetes on alpha-crystallins and other heat shock proteins in the eye

Abstract

Diabetes and its related complications represent a major growing health concern and economic burden worldwide. Ocular manifestations of diabetes include cataractogenesis and retinopathy, the latter being the leading cause of blindness in the working-age population. Despite numerous studies and recent progress, the exact pathophysiology of the disease remains to be fully elucidated and development of new and improved therapeutic strategies for this chronic condition are greatly needed. Heat shock proteins (Hsps) are highly conserved families of proteins, which are generally regarded as protective molecules that play a wide variety of roles and can be expressed in response to different types of cellular stresses. In recent years, numerous studies have reported their implication in various ocular diseases including diabetic retinopathy. The present review focuses on the potential implication of Hsps in ocular diabetic complications and discusses their specific mechanisms of regulation with respect to their expression, functions and alteration during diabetes. The review will conclude by examining the potential of Hsps as therapeutic agents or targets for the treatment of diabetic retinopathy.

Pro-inflammatory cytokines downregulate Hsp27 and cause apoptosis of human retinal capillary endothelial cells

“…HG alone also reduced Hsp27 phosphorylation. Together, these data suggest that under diabetic conditions, the combined actions of HG and cytokines could markedly deplete Hsp27 and its phosphorylation in HREC, consistent with our previous data of reduction of the rodent homolog, Hsp25 in the STZ-mouse model [31]. We also tested whether cytokines ± HG treatments as above altered the αB-crystallin levels in HREC.…”

“…Moreover, whether Hsp27 is downregulated in endothelial cells of diabetic retina is unknown. There is evidence for upregulation of heat shock proteins in general and the specific upregulation of Hsp27 in the diabetic retina [31, 41, 42]. It is possible that there may be an overall increase in these proteins in diabetic retina, but at the same time locally within capillary endothelial cells, there may be a decrease.…”

Diabetic Retinopathy—Update on Prevention Techniques, Present Therapies, and New Leads

“…99,100 Conversely, levels of ocular crystallins and other heat shock proteins (HSPs) that normally elicit neuroprotective responses in stress conditions have been shown to be overexpressed in the diabetic retina; however, their protective functions are impaired. 101–103 Erythropoietin (EPO) is another agent proved imperative for retinal cell survival and compensatory mechanisms in response to early neuronal damage in retinopathy; however, its upregulation in advanced stages of disease development can alternately contribute to neovascularization and worsen PDR. 104 Studies are underway to further characterize the therapeutic potential of these natural protective agents, either in their native or slightly modified form, in early stages of diabetic retinopathy.…”

Heat shock protein‐70 and hypoxia inducible factor‐1α in type 2 diabetes mellitus patients complicated with retinopathy

“…Heat shock proteins (HSPs) are a group of ubiquitous, well‐described proteins which are generally regarded as protective molecules that play a wide variety of roles and can be expressed in response to different types of cellular stresses (Heise & Fort ). They are expressed in conditions of thermal, ischaemic and oxidative stress (Morteza et al.…”