Age as an independent risk factor for severity of experimental choroidal neovascularization.
PURPOSE: For many vascular diseases, aging appears to be an independent risk factor for severity of vascular complications, and blood vessels of aged individuals often demonstrate exaggerated repair responses to injury. This study was undertaken to determine the influence of aging on the severity of neovascularization in a mouse model of laser-induced choroidal neovascularization (CNV). METHODS: CNV was induced in young (2-month-old) and aged (16-month-old) C57BL/6 mice by making four separate choroidal burns in each eye with a diode red laser (650 nm). At 1, 2, and 4 weeks, the left eyes were removed for histopathology, and the right eyes were removed for flatmount analysis of CNV surface area, vascularity, and cellularity. RESULTS: Aged mice demonstrated a much larger area of CNV than did young mice (3.81 +/- 1.28 vs. 1.36 +/- 0.99 disc areas, P < 0.001) at 2 weeks, when the lesions showed maximum growth. Aged mice also demonstrated higher ratios for vascularity and cellularity of the CNV (1.34 +/- 0.06 vs. 1.03 +/- 0.11, P < 0.0001 and 4.06 +/- 1.19 vs. 1.91 +/- 0.81, P < 0.002 at 2 weeks, respectively). Histopathology revealed that CNV in older eyes was larger, thicker, and more cellular than in young eyes. CONCLUSIONS: In mice, age is associated with more severe CNV, defined as larger surface area, greater vascularity, and greater cellularity. Age-related systemic susceptibility factors, independent of local changes in the retina, may contribute to the greater severity of CNV in older than in younger individuals.
Espinosa-Heidmann, DG; Suner, I; Hernandez, EP; Frazier, WD; Csaky, KG; Cousins, SW
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