The current focus of the lab focuses on mechanisms for the efficient targeting of phagocytosed material for waste processing in the visual system which we have expanded to include bacterial pathogenesis, specifically Porphyromonas gingivalis (P.g.). The central the theme of our studies is to understand how a cell identifies, tags and disposes of what it perceives as “trash”- those components that are no longer useful or wanted. Trash however is a tricky thing- it may be recycled as in the case of components ingested during phagocytosis by the epithelium or it made be immediately tagged for degradation as is the case with bacteria ingested by immune cells. The inability to efficiently and adequately degrade phagosomes leads to both degenerative and inflammatory disease. ; in the RPE incomplete degradation of phagosomes leads to the accumulation of liposfuscin contributing to age-related retinal degenerative diseases. Macrophages, one of the first lines of host defense, target ingested pathogens for degradation. Often, however, these pathogens hijack and subvert the normal degradative pathway. One such example is the subversion by Porphyromonas gingivalis (P.g.) of autophagosome dependent degradation. Cells utilize numerous processes to identify and target ingested material for degradation these include phagocytosis and autophagy. Recently, a novel hybrid pathway that utilizes components of both of these pathways has been characterized and is termed LC3 associated phagocytosis (LAP). Using a combination of confocal imaging and biochemical techniques as well as in vitro and in vivo models we have characterized this LAP process in the RPE’s function as a professional phagocyte. Moreover, we have identified a novel modulator of LAP, a small LC3 binding protein called melanoregulin, MREG. Our current studies focus on the generation of neuroprotectin D1 by the RPE from LAP processes as well as the metabolic consequences to the RPE when ketone body production from ingested fatty acids is compromised. When OS phagocytes is compromised and degradation delayed as with loss of LC3B, boht in vivo and in vitro models phenocopy pathologies associated with Age-related macular degeneration (AMD). MREG is also involved in maintaining the size of intracellular melanosomes, we have shown that loss of MREG rescues the phenotype of Ocular Albinism -1 (OA1) in an animal model. OA1 is a rare genetic disorder leading to blindness and often deafness at a young age. Continuation of these studies is underway through collaborators at the Vision of Color Foundation.