Redistribution of Aquaporin Proteins in Retinal Blood Vessels in Human Diabetic Retinopathy

Diabetic macular edema, the primary cause of vision loss in non-proliferative diabetic retinopathy (NPDR), is traditionally attributed to microvascular leakage but may also involve structural and caliber change in large retinal vessels. This study investigated the spatial distributions of key aquaporins from the aquaporin family mediating water transport or membrane stability in donor human retinas with diabetic retinopathy (DR).

Human donor retinas were fixed, sectioned and labeled for immunohistochemistry using antibodies against Aquaporin 0 (AQP0), Aquaporin 1 (AQP1) and Aquaporin 4 (AQP4). Labeling was performed in combination with vascular and cellular markers including calbindin, A kinase anchor protein-2 (AKAP-2), vimentin, glial fibrillary acidic protein (GFAP), Kir4.1, and collagen IV. Images were acquired using high-resolution laser scanning confocal microscopy and analyzed using ImageJ.

AQP0 distribution in the inner retina remained unchanged in DR. In contrast, both AQP1 and AQP4 exhibited marked redistribution within and around large retinal vessels. Specifically, AQP1, typically confined to the endothelium of superficial vessels, was detected in the middle layer of vessel walls in DR. AQP4, normally localized to the ganglion cell layer and associated with vimentin-positive Müller glia processes, was observed in the outer vessel layers, even in the absence of significant GFAP upregulation.

The novel localization of AQP1 within the vessel wall may reflect altered spatial organization of water transport pathways within retinal vessel walls, contributing to impaired contractile function. These findings indicate that alterations in aquaporin distribution may be associated with vascular remodeling observed in DR.