Alpha-Smooth Muscle Actin-Positive Perivascular Cells in Diabetic Retina and Choroid

Structural alterations of pericytes in microvessels are important features of diabetic retinopathy. Although capillary pericytes had been known not to have alpha-smooth muscle actin (alpha SMA), a recent study revealed that a specific fixation method enabled the visualization of alpha SMA along retinal capillaries. In this study, we applied snap-fixation in wild type and streptozotocin-induced diabetic mice to evaluate the differences in vascular smooth muscle cells of the retina and the choroid. Mice eyeballs were fixed in ice-cold methanol to prevent the depolymerization of filamentous actin. Snap-fixated retina showed alpha SMA expression in higher-order branches along the capillaries as well as the arterioles and venules, which were not detected by paraformaldehyde fixation. In contrast, most choriocapillaris, except those close to the arterioles, were not covered with alpha SMA-positive perivascular mural cells. Large choroidal vessels were covered with more alpha SMA-positive cells in the snap-fixated eyes. Diabetes induced less coverage of alpha SMA-positive perivascular mural cells overall, but they reached higher-order branches of the retinal capillaries, which was prominent in the aged mice. More alpha SMA-positive pericytes were observed in the choroid of diabetic mice, but the alpha SMA-positive expression reduced with aging. This study suggests the potential role of smooth muscle cells in the pathogenesis of age-related diabetic retinopathy and choroidopathy.