Complement activation, lipid metabolism, and mitochondrial injury: Converging pathways in age-related macular degeneration
Li Xuan Tan,
Colin J. Germer,
Nilsa La Cunza,
Aparna Lakkaraju
Affiliations
Li Xuan Tan
Department of Ophthalmology, School of Medicine, University of California, San Francisco, CA, USA
Colin J. Germer
Department of Ophthalmology, School of Medicine, University of California, San Francisco, CA, USA; Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, CA, USA
Nilsa La Cunza
Department of Ophthalmology, School of Medicine, University of California, San Francisco, CA, USA; Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, CA, USA
Aparna Lakkaraju
Department of Ophthalmology, School of Medicine, University of California, San Francisco, CA, USA; Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, CA, USA; Department of Anatomy, School of Medicine, University of California, San Francisco, CA, USA; Corresponding author. Department of Ophthalmology, University of California, San Francisco, 10 Koret Way, Room 233, San Francisco, 94143, CA, USA
The retinal pigment epithelium (RPE) is the primary site of injury in non-neovascular age-related macular degeneration or dry AMD. Polymorphisms in genes that regulate complement activation and cholesterol metabolism are strongly associated with AMD, but the biology underlying disease-associated variants is not well understood. Here, we highlight recent studies that have used molecular, biochemical, and live-cell imaging methods to elucidate mechanisms by which aging-associated insults conspire with AMD genetic risk variants to tip the balance towards disease. We discuss how critical functions including lipid metabolism, autophagy, complement regulation, and mitochondrial dynamics are compromised in the RPE, and how a deeper understanding of these mechanisms has helped identify promising therapeutic targets to preserve RPE homeostasis in AMD.
