Neuronal and synaptic connectivity impairment along with the vascular alterations in the macula of diabetic patients

Abstract

Purpose: Retinal neurodegeneration in diabetic patients appears to occur along with the vascular abnormalities. Some structural and functional changes have been described in the retina of these patients. The aim was to describe the morphological alterations present in the retinal cells and the vascular network in the macula of human donor with diabetes. Methods: Retinas of human donor with diabetes or diabetic retinopathy (n = 5) and control (n = 3) were processed in cross‐sections or flat mount retinas. The vascular network and the retinal cells were analysed in the macula through immunohistochemistry and confocal microscopy. Analysis of the vessel density was performed with the Angio‐tool software. Results: Diabetic and control group had a mean age of 60 ± 10 and 62 ± 2 years, respectively. Capillary bends, vascular loops, microaneurysms and an increase of the vascular density were the main findings in the intermediate and deep capillary plexuses of the diabetic group. Disruption of the basement membrane of the retinal vessels and tractions due to the epiretinal membrane were observed in the superficial vessels. Interpericyte tunnelling nanotubes appeared altered in the plexuses of the diabetic retinas. Endothelial cell marker was accumulated inside the microaneurysms, and microglial nodules were surrounding them. Disruption of the external limiting membrane and swelling of Müller cells were present. Disorganization or loss of the outer plexiform layer observed with bassoon, vesicular glutamate transporter and synaptophysin as well as sprouting of the horizontal cells existed in some diabetic retinas. Cone photoreceptors seem to extend their axons to maintain the synaptic connectivity in the intraretinal cysts. Synaptic terminals of the bipolar cells in the plexiform layers were altered. Conclusions: In addition to the specific vascular changes, alterations in the synaptic connectivity and the morphology of retinal cells are present in the fovea of diabetic patients.