Alpha-Smooth Muscle Actin Expression and Parafoveal Blood Flow Pathways Are Altered in Preclinical Diabetic Retinopathy

PURPOSE: To investigate differences in alpha smooth muscle actin (αSMA) expression and parafoveal blood flow pathways in diabetic retinopathy (DR). METHODS: Human donor eyes from healthy subjects (n = 8), patients with diabetes but no DR (DR–; n = 7), and patients with clinical DR (DR+; n = 13) were perfusion labeled with antibodies targeting αSMA, lectin, collagen IV, and filamentous actin. High-resolution confocal scanning laser microscopy was used to quantify αSMA staining and capillary density in the parafoveal circulation. Quantitative analyses of connections between retinal arteries and veins within the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were performed. RESULTS: Mean age between the groups was not different (P = 0.979). αSMA staining was seen in the SVP and ICP of all groups. The DCP was predominantly devoid of αSMA staining in control eyes but increased in a disease stage–specific manner in the DR– and DR+ groups. The increase in αSMA staining was localized to pericytes and endothelia of terminal arterioles and adjacent capillary segments. Capillary density was less in the DCP in the DR+ group (P < 0.001). ICP of the DR– and DR+ groups received more direct arteriole supplies than the control group (P < 0.001). Venous outflow pathways were not altered (all P > 0.284). CONCLUSIONS: Alterations in αSMA and vascular inflow pathways in preclinical DR suggest that perfusion abnormalities precede structural vascular changes such as capillary loss. Preclinical DR may be characterized by a “steal” phenomenon where blood flow is preferentially diverted from the SVP to the ICP and DCP.