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Papers by Silvia Finnemann

Experimental Eye Research, 2014

retinal pigment epithelium phagocytosis signaling photoreceptor outer segment renewal engulfment ... more retinal pigment epithelium phagocytosis signaling photoreceptor outer segment renewal engulfment a b s t r a c t 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.

Journal of Experimental Medicine, 2004

Daily phagocytosis by the retinal pigment epithelium (RPE) of spent photoreceptor outer segment f... more Daily phagocytosis by the retinal pigment epithelium (RPE) of spent photoreceptor outer segment fragments is critical for vision. In the retina, early morning circadian photoreceptor rod shedding precedes synchronized uptake of shed photoreceptor particles by RPE cells. In vitro, RPE cells use the integrin receptor ␣ v ␤ 5 for particle binding. Here, we tested RPE phagocytosis and retinal function in ␤ 5 integrin-deficient mice, which specifically lack ␣ v ␤ 5 receptors. Retinal photoresponses severely declined with age in ␤ 5 Ϫ / Ϫ mice, whose RPE accumulated autofluorescent storage bodies that are hallmarks of human retinal aging and disease. ␤ 5 Ϫ / Ϫ RPE in culture failed to take up isolated photoreceptor particles. ␤ 5 Ϫ / Ϫ RPE in vivo retained basal uptake levels but lacked the burst of phagocytic activity that followed circadian photoreceptor shedding in wild-type RPE. Rhythmic activation of focal adhesion and Mer tyrosine kinases that mediate wild-type retinal phagocytosis was also completely absent in ␤ 5 Ϫ / Ϫ retina. These results demonstrate an essential role for ␣ v ␤ 5 integrin receptors and their downstream signaling pathways in synchronizing retinal phagocytosis. Furthermore, they identify the ␤ 5 Ϫ / Ϫ integrin mouse strain as a new animal model of age-related retinal dysfunction.

Experimental Eye Research, 2014

retinal pigment epithelium phagocytosis signaling photoreceptor outer segment renewal engulfment ... more retinal pigment epithelium phagocytosis signaling photoreceptor outer segment renewal engulfment a b s t r a c t 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.

Journal of Experimental Medicine, 2004

Daily phagocytosis by the retinal pigment epithelium (RPE) of spent photoreceptor outer segment f... more Daily phagocytosis by the retinal pigment epithelium (RPE) of spent photoreceptor outer segment fragments is critical for vision. In the retina, early morning circadian photoreceptor rod shedding precedes synchronized uptake of shed photoreceptor particles by RPE cells. In vitro, RPE cells use the integrin receptor ␣ v ␤ 5 for particle binding. Here, we tested RPE phagocytosis and retinal function in ␤ 5 integrin-deficient mice, which specifically lack ␣ v ␤ 5 receptors. Retinal photoresponses severely declined with age in ␤ 5 Ϫ / Ϫ mice, whose RPE accumulated autofluorescent storage bodies that are hallmarks of human retinal aging and disease. ␤ 5 Ϫ / Ϫ RPE in culture failed to take up isolated photoreceptor particles. ␤ 5 Ϫ / Ϫ RPE in vivo retained basal uptake levels but lacked the burst of phagocytic activity that followed circadian photoreceptor shedding in wild-type RPE. Rhythmic activation of focal adhesion and Mer tyrosine kinases that mediate wild-type retinal phagocytosis was also completely absent in ␤ 5 Ϫ / Ϫ retina. These results demonstrate an essential role for ␣ v ␤ 5 integrin receptors and their downstream signaling pathways in synchronizing retinal phagocytosis. Furthermore, they identify the ␤ 5 Ϫ / Ϫ integrin mouse strain as a new animal model of age-related retinal dysfunction.

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