Abstract
Purpose :
Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, and its prevalence is growing rapidly due to the increasingly aging global population. Choroidal neovascularization (CNV) is the aberrant growth of blood vessels beneath the retina that characterizes the most severe form of AMD. Mechanisms underlying the improper vascularization of the choroid are not entirely understood. A handful of microRNAs become dysregulated in ocular tissue during the progression of AMD and of these miR-34a may play a significant role due to its involvement in many gene pathways relating to inflammation, angiogenesis, and cellular senescence. Although a positive correlation has been previously established between miR-34a and CNV in the ocular tissue of patients suffering from wet AMD, there has yet to be a causal link made between the two. Therefore, we hypothesized that the upregulation of miR-34a in ocular tissue with age promotes CNV.
Methods :
To investigate the role of miR-34a in CNV, we used an experimental mouse model of laser-induced CNV. Further analysis using bulk-RNA sequencing analysis of choroidal cell lysates revealed downstream targets of miR-34a likely to be implicated in the progression of CNV.
Results :
Using whole-body miR-34a-/- mice we found that CNV lesions were significantly decreased in the absence of miR-34a compared to wild-type controls. Additionally, preliminary RNA-seq analysis revealed genes that are potential downstream targets of miR-34a in the context of laser-induced CNV.
Conclusions :
Ultimately, we found that miR-34a may promote CNV by downregulating key genes that regulate angiogenesis in the choroid. Investigating the underlying mechanisms of miR-34a in promoting CNV will lead to an improved understanding of AMD pathogenesis and may provide novel treatment strategies for this debilitating disease.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.