The Novel Role of an Intracellular Nuclear Receptor in AMD Pathogenesis

This project aims to uncover the mechanisms by which a lipid-sensing nuclear receptor RORa links lipid dysregulation with abnormal macrophage recruitment and chronic inflammation in AMD pathogenesis.

Age-related macular degeneration (AMD) is a leading cause of blindness among people aged 60 and older. It is a multifactorial disease involving multiple cellular pathways, among which lipid dysregulation and inflammation are major pathogenic factors. Researchers will investigate the role of a lipid-sensing nuclear receptor retinoic acid-related orphan receptor alpha (RORa) in regulating chronic subretinal inflammation to elucidate AMD pathogenesis. They will assess if genetic deletion of RORa in a type of inflammatory cells may lead to lipid dysregulation and chronic inflammation.

Lipid dysregulation is implicated in AMD pathogenesis, yet the mechanisms through which lipid dysregulation in macrophages/microglia leads to chronic inflammation impact AMD is not fully clear. This research proposal aims to fill this knowledge gap by investigating a novel role of a nuclear receptor retinoic acid-related orphan receptor alpha (RORa) that may link lipid dysregulation and chronic subretinal inflammation involving macrophage/microglia in AMD pathogenesis. This project will provide a potential new druggable target RORa in resolving chronic inflammation in AMD.

Successful completion of this proposal will advance the field of AMD research by uncovering new knowledge on how a novel lipid regulator RORa may transcriptionally link lipid dysregulation and chronic inflammation in early AMD disease processes. Such information may provide new breakthroughs and new druggable molecular targets for designing potential AMD therapies.