My laboratory specializes in the mechanisms of cell death, cell survival, and the consequences of these processes on the immune and visual systems. This unique perspective has allowed us to make many important contributions to understanding the molecular basis of blinding eye diseases and the relationship between the eye and the immune system. We were the first to describe FasL (CD95L) as a mediator of immune privilege in the eye, where expression of this protein on ocular cells induces apoptosis in invading inflammatory cells. This protects the visual axis from damaging inflammation. FasL expression is also critical to the success of corneal transplants. We were first to determine that only certain subtypes of macrophages promoted angiogenesis in AMD models, while others were inhibitory. We have also explored the role of the immune system in models of AMD and are exploring the idea that targeting the immune privilege might lead to effective therapies for retinal disease. This laboratory also has considerable expertise in the phagocytosis of apoptotic cells by dendritic cells and the impact of this process on the immune response. We are now putting our expertise (and significant effort) toward understanding the role of autophagy in the functions of the eye and CNS, as well as examining the consequences of the deletion of crucial autophagy genes in the cells of the eye. We have shown that autophagy is important for retinal pigment epithelium (RPE) phagocytosis of photoreceptors outer segments, the RPE visual cycle, and the regulation of phototransduction in the rod photoreceptors. Recently, we demonstrated that cones uniquely utilize autophagic mechanisms to maintain structure and function. Specifically, induced autophagy protects cone-mediated vision (daytime vision) from light and metabolic stress; while basal autophagy (in the form of mitophagy) prevents cell damage and maintains cone energy supplies by continuously removing oxidatively damaged mitochondria.

Current projects in the lab:
Müller glial cells and Immune privilege of the eye: We are undertaking studies to determine the precise role of Müller glial cell autophagy in the immune privilege of the eye. Our approach utilizes cell-type specific knockouts of essential autophagy genes coupled with ocular inflammatory models of retinal disease. scRNA-seq analysis is employed to study gene expression in Müller cells to understand the molecular basis of immune privilege.
Müller glial cell phagocytosis: In phagocytic cells (e.g. macrophages and RPE cells) phagocytosis of extracellular material (bacteria, photoreceptor outer segments) engages elements of autophagy pathway. This process is termed LC3-associated phagocytosis (or LAP) and disruption of the pathway can lead to autoimmunity and vision loss. Muller cells are also phagocytic, thus, we examining the role of LAP in Müller cells by testing the idea that autophagy supports phagocytosis in Müller cells promoting their anti-inflammatory properties.
Autophagy and cone photoreceptor function: The function of cones as our daytime photoreceptors depends critically on the rapid recovery of their sensitivity after exposure to bright light, a process known as dark adaptation. We are studying the role of autophagy in cone-driven photopic dark adaptation. Recent studies suggest that without autophagy cone dark adaptation is slowed. When autophagy is enhanced in normal cones by systemic starvation dark adaptation is accelerated. Whether autophagy regulates dark adaptation at the level of the visual cycle or synaptic transmission is currently under study. 

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