Neuronal Degeneration and Glial Activation in the Absence of Vascular Changes in Human Retinas of Patients With Diabetes.

Purpose: This study assessed retinal cells in the macula of human donors with diabetes with or without retinopathy. Methods: Seventeen human donor retinas were classified as diabetes mellitus (DM, n = 7), diabetes with diabetic retinopathy (DR, n = 3), or control (n = 8). Macular transversal sections were analyzed for photoreceptors, bipolar cells, horizontal cells, ganglion cells, their synaptic connections, and Müller cells using immunohistochemistry and confocal microscopy. The densities of bipolar cells, horizontal cells, and ganglion cells and the thickness of the inner plexiform layer (IPL) were quantified around the fovea. Results: In the macula, cone photoreceptors elongated their axons to establish synapses with bipolar and horizontal cells in intraretinal cysts. Bipolar cells were reduced in the DM group compared to the control (P < 0.001), and rod bipolar cells showed morphological alterations in the cell body and synaptic terminals in both diabetic groups. Morphological changes were observed in both plexiform layers, with a decrease in the IPL thickness in DR. Horizontal cell terminals sprouted into the outer and inner retina in DR, despite no density differences existing between DM and control (P = 0.498). Ganglion cell density was reduced in the DM retinas compared to control (P < 0.001). Müller cells exhibited thickening of their cell bodies and end feet in all diabetic retinas. Conclusions: The degeneration of neurons and synaptic connectivity within the macula in individuals with DM, even in the absence of clinical vascular signs, is associated with impaired visual function. These early changes suggest potential new biomarkers for imaging techniques and emphasize the need for therapies for diabetic patients without clinical signs.