Abstract
Purpose :
Aberrant ocular angiogenesis contributes to profound vision loss in conditions such as neovascular age-related macular degeneration (nvAMD), proliferative diabetic retinopathy (DR), retinopathy of prematurity (ROP), and ischemic retinal vein occlusion. Telomerase, a pivotal enzyme associated with telomere maintenance, has been extensively linked to endothelial cell proliferation, survival, migration, and invasion within the realm of tumor angiogenesis. Despite these known roles, its potential involvement in pathological ocular angiogenesis is still a relatively unexplored area. This study aims to unravel the proangiogenic impact of telomerase by employing a mouse model of laser-induced choroidal neovascularization (CNV).
Methods :
CNV was induced by laser injury in 10-12 week old C57BL/6J wild-type (WT), Tert−/−,and Terc−/− mice. Seven days after the laser injury, eyes were dissected and confocal microscopic imaging of CNV lesions stained with FITC-labeled Griffonia Simplicifolia Lectin I (GSL1) Isolectin B4 was performed. CNV lesion area and volumes were measured using Nikon NIS-Elements NIS.ai image analysis suite.
Results :
We observed significantly reduced CNV lesion area and volume in both Tert–/– the Terc–/– mice compared to WT mice. Since Tert–/– and Terc–/– mice were derived from heterozygous breeders (Tert+/− and Terc+/–), these knockout mice are not expected to have shortened telomeres. These results suggest that proangiogenic activity of Tert and Terc are independent of their canonical telomerase maintenance function.
Conclusions :
Telomerase has a proangiogenic activity in this laser-induced CNV mouse model. These findings highlight the new roles of telomerase components in ocular angiogenesis and suggest potential avenues for therapeutic interventions.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.