Disconnection Between Microvascular Damage and Neurodegeneration in Early Diabetic Retinopathy

Abstract

Aim: Diabetic retinopathy (DR) is a common complication of diabetes mellitus and can result in vision loss. Early clinically diagnosed signs of DR are linked to vascular damage, impacting on the neural retina typically at later stages. However, vascular changes and potential effects on neural cells before clinical diagnosis of DR are less understood. Methods: To learn more about the earliest stages of DR we studied postmortem retina from diabetic donors who did not have clinical DR. Histological phenotyping and quantitative analysis were carried out on retina from 14 donors (3 controls, 10 diabetics, and 1 DR case) to examine capillary loss in the deeper vascular plexus (DVP) and the superficial vascular plexus (SVP) of the retinal vasculature and to study effects on the neural retina. Results: The advanced DR case exhibited profound vascular and neural damage as expected, whereas none of the ten randomly selected diabetic donors had any DR signs that would have been diagnosed clinically. Within that group, two showed very minor capillary dropout in the SVP, whilst in the remaining diabetic cases the SVP was indistinguishable from the controls. In contrast, over half of the diabetic retinas showed capillary dropout in the DVP and increased capillary diameter. Furthermore, a pan retinal loss of inner nuclear layer cells was observed in those diabetics with capillary dropout compared to the controls (p<0.05), but there was no local spatial correlation between neural cell loss and capillary dropout. Conclusions: Our study has established a novel histological biomarker for diabetes related tissue damage at the earliest stages of DR in human postmortem retina, which appears to be common in people with diabetes before DR can be clinically diagnosed. Furthermore, the diffuse neural loss in the INL at this very early stage of DR suggests a very close interplay between vascular and neural elements or diabetes impacting on both readouts independently.

Advances in Structural and Functional Retinal Imaging and Biomarkers for Early Detection of Diabetic Retinopathy

“…This review has delved into this topic in detail, aiming to elucidate the early structural and functional alterations in DR. A preprint study proposed that by employing histological phenotyping and quantitative analysis of postmortem retina from diabetic donors without clinical DR, the observed disparity between localized capillary dropout and widespread neural loss within the inner nuclear layer (INL) suggests that microvascular loss might not directly lead to neurodegeneration during the early stages of DR. This indicated that diabetes could independently impact these two indicators [168]. Both our review and this article suggest that combining structural and functional examinations may represent the optimal strategy for enhancing early detection of DR. Healthcare institutions can implement both structural and functional examinations for patients at high risk of developing DR, tailoring the approach according to their respective capabilities and resources.…”