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Patrice Fort, Sean Grafton, Katelyn Roth; Specific Role and Regulation of αA- and αB-Crystallins in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2684.
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To better characterize the specific and respective roles of αA- and αB-crystallin, the two members of the α-crystallin sub-family in the retina and how diabetes affects them. We previously demonstrated that they are upregulated in diabetic conditions 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 remained to be clarified.
Specific cellular localization of α-crystallins in the retina of diabetic and non-diabetic littermate mice was analyzed by immunohistochemistry. A similar approach was used to characterize the localization of α-crystallins in the human retina and how it is affected by diabetes and diabetic retinopathy. In addition α-crystallins knockout mice were used to dissect the respective functions of α-crystallins in the retina in control conditions and in response to diabetes. Retinal function was analyzed using non-invasive methods such as optical coherence tomography and electroretinographic recordings whereas specific retinal cell survival was analyzed using cell-death assay and immunohistochemistry.
We demonstrated that αA- and αB-crystallin were both upregulated in diabetic conditions but that their cellular localization was different. While αA-crystallin shows mainly a specific upregulation in Muller glial cells, αB-crystallin present with a more diffuse staining concentrated in the inner retina. We previously showed that the retina of mice lacking either αA- or αB-crystallins did not present any anatomical or functional defects under normal conditions. Interestingly while the absence of αA- or both αA- and αB-crystallin led to a larger increase in retinal cell death and perturbations of retinal functions during diabetes, absence of αB-crystallin prevented it.
This work clearly demonstrates the independent and specific respective roles of αA- and αB-crystallin in the retina especially in the context of chronic disease conditions such as diabetes. αA- and αB-crystallin proteins clearly display a different localization in the retina as well as different impact on retinal function in diabetic retinopathy. 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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