Abstract
Purpose :
Most common retinal diseases are age related, but global mechanisms for this phenomenon are unclear. Since it is well-established that blood vessels change with age (reduced plasticity, modified neurovascular communication, altered metabolism, etc.), one potential explanation centers on age-dependent retinal vascular alterations. We used a newly developed retinal vasculature analysis workflow to compare the vasculature of aged and young adult mice.
Methods :
Retinas were collected from young (14 weeks, n=6) and old (82-85 weeks, n=3) wild type mice and stained with antibodies to CD31 (endothelium) and Collagen IV (COLIV; vascular basement membrane). We performed z-stack confocal microscopy to visualize all three retinal capillary plexi (RCPs). The intersections of the entire retinal capillary network were quantified with Sholl analysis (vascular complexity). Anatomical and spatial features of individual RCPs (total capillary junctions, capillary vessel length, capillary vessel diameter, acellular capillaries) were determined using a recently published workflow utilizing ImageJ and AngioTool software.
Results :
Retinal vascular complexity was significantly reduced (p≤0.0001) in aged retinas. For both CD31 and COLIV, total capillary junctions and total capillary vessel length were reduced in all three plexi (superficial retinal capillary plexus [SRCP], intermediate retinal capillary plexus [IRCP], and deep retinal capillary plexus [DRCP]) in aged retinas. Capillary vessel diameter showed plexus-specific changes in aged retinas. Only the IRCP manifested substantial vessel dilatation (CD31 and COLIV; both p≤0.01). Furthermore, the IRCP showed significant capillary loss (increased acellular capillaries, p≤0.0001). Additional studies with transmission electron microscopy focused on the IRCP and its interaction with the blood retina barrier (BRB) are ongoing.
Conclusions :
The retinal vasculature of aged retinas shows multiple phenotypes when compared to young adult retinas. While some phenotypes are seen across all RCPs, the IRCP, a component of the BRB, displays several unique phenotypes. Finally, understanding age related, plexus-specific phenotypes may be useful for early diagnosis and prediction of disease outcomes.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.