A major function of the retinal pigment epithelium (RPE) is to ingest and degrade outer segment disk membranes from the photoreceptor cells. This catabolic role in the turnover of the phototransductive disk membranes is essential for the viability of the photoreceptor cells. The efficiency by which this role is carried out is also important for the health of the RPE cells, with related defects leading to pathogenesis. The ingestion and maturation of the ensuing phagosomes is dependent upon motor protein activity. The proposed research focuses on understanding this motor protein activity and the interactions of phagosomes with endo-lysosomes. The approach will include high-speed, live-cell imaging analysis in order to elucidate the dynamics of underlying cellular and molecular mechanisms. In a series of studies, the function of the Usher 1B protein, MYO7A, and microtubule motors will thus be investigated, in order to provide a detailed understanding of how these motors move POS phagosomes in RPE cells, and how the resulting phagosome motility facilitates phagosome maturation. The results will provide a new level of understanding of a central function of the RPE, with high relevance to retinal aging and disease.
The proposed research will provide a fundamental mechanistic understanding of the way phagosomes, originating from photoreceptor disk membranes, are transported and degraded in the retinal pigment epithelium (RPE). Its focus is on the motility of phagosomes and endo-lysosomes, which, when compromised, leads to RPE pathology. The research is relevant to retinal aging and disease.
| Esteve-Rudd, Julian; Hazim, Roni A; Diemer, Tanja et al. (2018) Defective phagosome motility and degradation in cell nonautonomous RPE pathogenesis of a dominant macular degeneration. Proc Natl Acad Sci U S A 115:5468-5473 |
| Hazim, Roni A; Volland, Stefanie; Yen, Alice et al. (2018) Rapid differentiation of the human RPE cell line, ARPE-19, induced by nicotinamide. Exp Eye Res 179:18-24 |
