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Patrice E Fort, Weixiang Zhang, Navasuja Chandrasekar, Katelyn Green; Regulation of Crystallins in Primates and Humans during Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5815.
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To better characterize the specific and respective roles of crystallin proteins in the retina and how diabetes affects them. We previously demonstrated that they are upregulated in various rodent models of diabetes and that their biochemical properties are affected by diabetes, however their exact implication and role in retinal function and how it is affected by diabetes in primates and humans remained to be clarified.
Detailed specific cellular localization of crystallin proteins in the retina of diabetic and non-diabetic age-matched rhesus monkeys and human donors was analyzed by immunohistochemistry. Similarly, the impact of diabetes on expression, phosphorylation and subcellular localization of crystallins was assessed using biochemical methods including immunoblotting and fractionation.
We demonstrated that several members of the crystallin proteins family were upregulated in a tissue and even cell-specific manner in diabetic conditions. While expressed in other region of the ocular tissue, several crystallins were primarily upregulated in the retina in a regional manner. Further, immunohistochemistry lead us to show that while several crystallin proteins were upregulated, they were expressed in specific and distinct cells of the retina. We further demonstrated that this upregulation was associated with changes in post-translational modification associated with alteration of function.
This work clearly demonstrates the effect of diabetes on crystallin proteins in primate and human ocular tissues and especially in the retina. Crystallin proteins are clearly affected in an ocular-tissue specific manner and display a different localization in the retina in response to diabetes. This study demonstrates how diabetes can alter the action of intrinsic protective mechanisms and how understanding such mechanisms is critical in order to prevent loss of vision in patients with diabetes.
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