Abstract
Purpose :
Ageing is linked with physical degeneration, which heightens the risk of several retinal diseases such as age-related macular degeneration (AMD), glaucoma, diabetic retinopathy, and hypertensive retinopathy. In order to develop successful interventions, it is imperative to investigate the fundamental mechanisms and reliable biomarkers of ageing and their contribution to the onset and progression of retinal disease. Extracellular vesicles (EVs) are nano-sized, lipid bilayer-delimited particles that are released by various cells. They are now recognized as playing crucial roles in modulating the cross talk between all kinds of cells as messengers by delivering cargos such as RNAs and proteins. Tissue EVs may thus lend insights into physiological and pathological mechanisms in the retina locally and directly. To this end, we performed a comparative proteomics analysis of the retina-derived small EVs (rdsEVs) and retina-derived large EVs(rdlEVs) from ageing mouse retinas using 4D label-free quantification proteomics, and profiled 360 retinas from 180 mice across three different ages.
Methods :
We first compared the protein content of rdsEVs and rdlEVs, and then further compared the two subpopulations of EVs in three different age groups.
Results :
We observed that the protein content of rdsEVs was more diverse than that of rdlEVs. We also found significant differences in the protein cargo of these isolated EVs, including several specific proteins, as well as in pyruvate metabolism and lysosomal pathways. The results of the rdsEVs comparison showed distinct differences in oxidative phosphorylation, lysosomal, thermogenesis pathways. Interestingly, we found distinctive metabolic pathways, Huntington's disease pathway, EGFR tyrosine kinase inhibitor resistance pathway, and spinocerebellar ataxia pathways amang rdlEVs.
Conclusions :
In conclusion, our work documents quantitative and qualitative differences between rdsEVs and rdlEVs. By providing a detailed comparison of two subpopulations of EVs isolated directly from retina tissues, we may better understand the function of EVs in the physiology and pathology of the ageing retina and their potential use in the discovery of biomarkers of retina ageing.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.