Synaptic connectivity impairment and neuronal degeneration in the macula of diabetic patients along with the vascular abnormalities

Abstract

Purpose : Vascular disturbances have been described as the main cause of vision loss in patients with diabetic retinopathy. However, neurodegeneration and synaptic connectivity is scarcely described in relation with the vision loss. The aim was to confirm whether morphological alterations occur in the retinal cells in the macula of human donor with diabetes.

Methods : Cross-sections or flat mount retinas were processed from human donor with diabetes (n=3) or diabetic retinopathy (n=2) and control (n=4). Immunohistochemistry and confocal microscopy were performed to assess the structure of the retinal and glial cells, their synaptic connectivity, and the vascular plexuses.

Results : Diabetic and control group had a mean age of 63±5 and 64±7 years, respectively. Müller cells were swollen, and the external limiting membrane was altered. Cone photoreceptors spread their axons to the inner retina in the presence of the intraretinal cysts. Loss or impairment of the outer plexiform layer was observed using antibodies against bassoon and vesicular glutamate transporter 1 (VGlut-1). Rod bipolar cells were altered mainly in their synaptic terminals in both plexiform layers and horizontal cells showed sprouting of their terminals in retinas with diabetic retinopathy. Microglia migrated towards the vessels gathering around the microaneurysms and endothelial cell marker was accumulated within them. Moreover, intermediate, and deep capillary plexuses of the diabetic group showed capillary bends and vascular loops. Epiretinal membrane caused tractions over the superficial vascular plexus and the basement membrane of the vessels was disrupted in the retinas with diabetic retinopathy.

Conclusions : Vascular abnormalities associated with the neuronal degeneration and the synaptic connectivity impairment may contribute to the vision loss in diabetic retinopathy.

Funding: Spanish Ministry of Science and Innovation (FEDER-PID2019-106230RB-I00). Spanish Ministry of Universities (FPU18/02964). National Institute of Health Carlos III (RETICS-FEDER RD16/0008/0016). Generalitat Valenciana (IDIFEDER/2017/064, PROMETEO/2021/024, ACIF/2020/203) and University of Alicante (MARSALAS21-35).

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.