Jayakrishna Ambati, MD
Year elected: 2007
Current membership category: Active
Age-related macular degeneration (AMD) is a principal cause of vision loss worldwide. It affects more Americans than do all cancers combined. The goal of the Ambati laboratory is to identify the molecular mechanisms underlying the development of AMD, determine the triggers of the angiogenic switch that converts this disease from an atrophic to a neovascular phenotype, and to develop novel therapeutics to prevent and treat this blinding condition. Our lab reported the first mouse model of AMD (Nature Medicine 2003) that recapitulates the salient features of the human disease and identified complement activation as an important angiogenic trigger in humans and mice (PNAS 2006). We also determined the molecular basis of corneal avascularity, a feature critical for optimal vision and one that can be exploited in developing new anti-angiogenic strategies (Nature 2006). We recently identified (Kleinman et al. Nature 2008) the immune receptor TLR3 as a surprising signaling receptor for small interfering RNAs (siRNAs) in a sequence-independent manner. We showed that siRNAs "generically" suppress angiogenesis in multiple mouse models by activating cell surface TLR3 rather than by triggering RNA interference. Concomitantly, we discovered (Yang et al. NEJM 2008) a hypomorphic polymorphism in TLR3 which confers protection against the atrophic form of AMD. These findings, which were covered in Commentaries by Nature Medicine and Nature Biotechnology, advance the nascent understanding of the multifunctional aspects of the immune system within the eye. We will continue our investigations into immunovascular biology with the goal of mapping this critical interface while creating more effective and tolerable medicines to treat neovascular diseases.
University of Virginia School of Medicine (Primary)
Alexander S. Krupnick, MD is the representative at this institution.