We study the organization of the retina in health and disease.  Toward this end, the phenotypes of transgenic and knockout/ knock-in mice carrying mutations in genes linked to retina dystrophies are analyzed.  We are particularly interested in mechanisms that lead to cell death, remodeling of the inner retina subsequent to photoreceptor (rod, cone) degeneration, and signal transduction in ON-bipolar cells.  In several neurodegenerative diseases, unfolded proteins accumulate intracellularly as insoluble inclusions, and appear to play a critical role in disease pathogenesis.  If native polypeptide conformations are lost through postsynthetic damage (e.g., environmental stresses) or genetic mutation, cells have elaborate mechanisms to prevent the aggregation of unfolded proteins, to attempt refolding, and, if refolding is impossible, to degrade the abnormal polypeptides into amino acids.  

We have shown that, in a mouse model for human adRP, the expression of a mutant rhodopsin (visual pigment) generates a protein that fails to mature, transport and support rod photoreceptor outer segment formation and, moreover, is cytotoxic.  What is the link between expression of a misfolded, mutant protein and induction of cell death?  To address questions such as this, we employ microscopy, gene cloning, and related techniques in cell and molecular biology.