Evaluation of sex differences in laser-induced choroidal neovascularization severity, phenotype and disease progression

Abstract

Age-related macular degeneration (AMD) progresses through two phases: a non-exudative “dry” stage that compromises vision but does not involve angiogenesis, and an angiogenic “wet” phase characterized by choroidal neovascularization (CNV), in which neovessels from the choroid break through the Bruch’s membrane to form neovascular lesions in the macula. If left untreated, CNV leads to permanent central blindness, which the current standard of care (anti-VEGF therapy) arrests but does not reverse. In laser-induced CNV, a laser is used to rupture the Bruch’s membrane, prompting the outgrowth of choroidal blood vessels in a wound healing response. This model was used to develop currently available CNV therapeutics, such as intravitreal injection of anti-VEGF and corticosteroid therapies and is considered a gold standard model for CNV. Laser-induced CNV thus remains a highly clinically relevant model of CNV secondary to AMD and other pathologies, such as myopia. A rapidly growing body of research suggests that the pathogenesis of myriad diseases is highly dependent on biological sex, yet most studies use only male animals. This highlights the importance of determining whether the severity and pathogenesis of commonly used models of disease, for example laser-induced CNV, differ between sexes. In the present study, we tracked longitudinal progression and pathogenesis of laser-induced CNV in male and female animals, and found that CNV severity did not differ between sexes. This lack of difference recapitulates findings in human patients with CNV, which have also identified that both sexes are at equal risk of CNV development in the contexts of both age-related macular degeneration induced CNV and myopic CNV.