Aging of the human choriocapillaris: Evidence that early pericyte damage can trigger endothelial changes

We examined human donor eyes (age: 56-94 years; N = 24), and found that CC pericyte damage preceded endothelial changes. With aging (>70 years), the sub-macular choroid accumulated debris in Bruch's membrane (BM). Of the debris content, the long-spaced collagens had a tendency to settle over the capillary basal lamina (BL), and this often resulted in endothelial projection into capillary lumen. Between 75 and 83 years, pericytes contained dark mitochondria, and their processes facing the BM debris showed partial loss of BL and intermediate filaments (IFs), when the endothelium remained unaltered. The endothelial changes appeared beyond 83 years, the abundance of IFs and autophagy reinforced their survival until late aging. TUNEL+ pericytes, and immunoreactivity to carboxymethyl lysine and 4-hydroxy 2-nonenal, but no nitro-tyrosine, was detected in aged CC walls. Iba-1+ dystrophic microglia were present in the vicinity of the CC. Our data indicate that (1) BM debris exerts pressure on the CC, leading to the damage of the capillary BL and pericyte processes (2) loss of IFs result in early pericyte destabilization (3) capillary wall undergoes lipid peroxidative and glycative damage, and (4) pericyte damage leads to late endothelial changes and ultimately CC loss. Future research should explore the normal ways of pericyte maintenance in the aging nervous system.PMID:34624336 | DOI:10.1016/j.exer.2021.108771
Source: Experimental Eye Research - Category: Opthalmology Authors: Source Type: research