Understanding photoreceptor outer segment phagocytosis: Use and utility of RPE cells in culture

•RPE cells in culture phagocytose photoreceptor outer segment fragments (POS).•Capacity and rate of POS phagocytosis depends on the specific type of cultured RPE.•Capacity and rate of POS phagocytosis depends on exact cell culture conditions.•RPE cells in situ and in culture use the same mechanism for POS phagocytosis.

RPE cells are the most actively phagocytic cells in the human body. In the eye, RPE cells face rod and cone photoreceptor outer segments at all times but contribute to shedding and clearance phagocytosis of distal outer segment tips only once a day. Analysis of RPE phagocytosis in situ has succeeded in identifying key players of the RPE phagocytic mechanism. Phagocytic processes comprise three distinct phases, recognition/binding, internalization, and digestion, each of which is regulated separately by phagocytes. Studies of phagocytosis by RPE cells in culture allow specifically analyzing and manipulating these distinct phases to identify their molecular mechanisms. Here, we compare similarities and differences of primary, immortalized, and stem cell-derived RPE cells in culture to RPE cells in situ with respect to phagocytic function. We discuss in particular potential pitfalls of RPE cell culture phagocytosis assays. Finally, we point out considerations for phagocytosis assay development for future studies.