The effect of age on wound healing in the laser induced choroidal neovascularization model

The laser induced model of choroidal neovascularization (LiCNV) is a commonly used in vivo rodent model to study neovascular age-related macular degeneration (nAMD), although progression of this model is not well understood. In this study we characterize and compare the longitudinal progression of wound healing of laser induced choroidal neovascular (CNV) lesions in young and old mice. Using 2-month and 12-month-old C57BL/6J mice and ocular computerized tomography (OCT), fluorescein and indocyanine green angiography we performed a longitudinal imaging analysis at 3-, 7-, 14- and 28-days following laser injury. This was compared with immunohistochemical analysis of the lesions at similar timepoints for markers of angiogenesis, fibrosis, epithelial-to-mesenchymal transition (EMT), and gliosis. OCT analysis determined an increased lesion volume in older mice. In contrast younger mice demonstrated earlier vascularization and fibrosis with no difference in neovascularization or leakage. Reactive gliosis occurs directly above the laser-induced CNV lesion in both ages. The RPE in this model encloses the lesion area by day 14 in both young and old mice. This study concludes that age is an important variable in some but not all aspects of laser-induced CNV.