Murine models of neovascular AMD revisited: Mechanistic pathways, immune-metabolic crosstalk, and the impact of aging and sex - PubMed
4 hours ago
- #Murine models
- #AMD research
- #Aging and sex in disease
- Neovascular AMD (nAMD) involves choroidal neovascularization, leakage, and fibrotic remodeling, with anti-VEGF therapy facing issues like resistance and fibrosis.
- Pathogenesis of nAMD involves metabolic dysfunction, oxidative stress, inflammation, hypoxia, and extracellular matrix changes in the outer retina.
- Key mechanisms include mitochondrial dysfunction, lipid handling in RPE, complement activation, inflammasome signaling, macrophage reprogramming, and hypoxia-driven VEGF expression.
- Murine models like laser-induced CNV, two-stage laser-induced fibrosis, and genetic systems (JR5558, VLDLR-deficient, CYP27A1-deficient) offer mechanistic insights.
- Aging and sex impact metabolism, immune responses, and wound healing, but many models use young, single-sex animals, underrepresenting these factors.
- The review stresses incorporating age and sex into preclinical models to enhance translational relevance and mechanistic understanding.