Abstract
Daily phagocytosis of shed photoreceptor outer segment fragments (POS) is a key task of the retinal pigment epithelium (RPE) in the retina. Lack or inefficiency of daily POS clearance causes early onset, rapid, and complete retinal degeneration in experimental animals and likely contributes to human blinding diseases such as retinitis pigmentosa and age-related macular degeneration (Dowling and Sidman, 1962, Gal et al., 2000). The phagocytic mechanism of the RPE belongs to a group of conserved non-inflammatory clearance pathways that mediate recognition and engulfment of apoptotic cells in both non-professional and professional phagocytic cells, such as fibroblasts and macrophages, respectively (Finnemann and Rodriguez-Boulan, 1999). These pathways share the use of phagocyte cell surface receptors such as the lipid scavenger receptor CD36 (Ryeom et al., 1996), the integrin adhesion receptor αv β5 (Finnemann et al., 1997; Miceli et al., 1997; Lin and Clegg, 1998) and the receptor tyrosine kinase Mer (MerTK) (D’Cruz et al., 2000; Nandrot et al., 2000). In vitro phagocytosis assays studying primary or permanent RPE in culture fed with isolated POS suggest that CD36 and MerTK participate in the engulfment step of the phagocytic process (Chaitin and Hall, 1983; Finnemann and Silverstein, 2001), while αv β5 integrin promotes POS recognition/binding and initiates a downstream cytoplasmic signaling cascade in the RPE (Finnemann et al., 1997). However, the precise function of these receptors and their roles in the intact retina are so far only poorly understood. Most recently, we have begun to study phagocytosis and receptor activity in animal models that lack αv β5 integrin or MerTK to determine how these different plasma membrane receptors of the RPE functionally interact to coordinate particle uptake.
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References
Chaitin, M. H., and Hall, M. O., 1983, Defective ingestion of rod outer segments by cultured dystrophic rat pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 24:812–820.
D’Cruz, P. M., Yasumura, D., Weir, J., Matthes, M. T., Abderrahim, H., LaVail, M. M., and Vollrath, D., 2000, Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum. Mol. Genet. 9:645–651.
Dowling, J. E., and Sidman, R. L., 1962, Inherited retinal dystrophy of the rat. J. Cell Biol. 14:73–109.
Edwards, R. B., and Szamier, R. B., 1977, Defective phagocytosis of isolated rod outer segments by RCS rat retinal pigment epithelium in culture. Science. 197:1001–1003.
Eliceiri, B. P., Puente, X. S., Hood, J. D., Stupack, D. G., Schlaepfer, D. D., Huang, X. Z., Sheppard, D., and Cheresh, D. A., 2002, Src-mediated coupling of focal adhesion kinase to integrin avb5 in vascular endothelial growth factor signaling. J. Cell Biol. 157:149–160.
Feng, W., Yasumura, D., Matthes, M. T., LaVail, M. M., and Vollrath, D., 2002, Mertk triggers uptake of photoreceptor outer segments during phagocytosis by cultured retinal pigment epithelial cells. J. Biol. Chem. 277:17016–17022.
Finnemann, S. C., 2003, Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors. EMBO J. 22:4143–4154.
Finnemann, S. C., Bonilha, V. L., Marmorstein, A. D., and Rodriguez-Boulan, E., 1997, Phagocytosis of rod outer segments by retinal pigment epithelial cells requires avb5 integrin for binding but not for internalization. Proc. Natl. Acad. Sci. U. S. A. 94:12932–12937.
Finnemann, S. C., and Rodriguez-Boulan, E., 1999, Macrophage and retinal pigment epithelium phagocytosis: apoptotic cells and photoreceptors compete for αvβ3 and αvβ5 integrins, and protein kinase C regulates αvβ5 binding and cytoskeletal linkage. J. Exp. Med. 190:861–874.
Finnemann, S. C., and Silverstein, R. L., 2001, Differential roles of CD36 and αvβ5 integrin in photoreceptor phagocytosis by the retinal pigment epithelium. J. Exp. Med. 194:1289–1298.
Gal, A., Li, Y., Thompson, D. A., Weir, J., Orth, U., Jacobson, S. G., Apfelstedt-Sylla, E., and Vollrath, D., 2000, Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa, Nat. Genet. 26:270–271.
Ilic, D., Furuta, Y., Kanazawa, S., Takeda, N., Sobue, K., Nakatsuji, N., Nomura, S., Fujimoto, J., Okada, M., and Yamamoto, T., 1995, Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature. 377:539–544.
Lin, H., and Clegg, D. O., 1998, Integrin αvβ5 participates in the binding of photoreceptor rod outer segments during phagocytosis by cultured human retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 39:1703–1712.
Miceli, M. V., Newsome, D. A., and Tate, Jr., D. J., 1997, Vitronectin is responsible for serum-stimulated uptake of rod outer segments by cultured retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 38:1588–1597.
Mullen, R. J., and LaVail, M. M., 1976, Inherited retinal dystrophy: primary defect in pigment epithelium determined with experimental rat chimeras. Science. 192:799–801.
Nandrot, E., Dufour, E. M., Provost, A. C., Pequignot, M. O., Bonnel, S., Gogat, K., Marchant, D., Rouillac, C., Sepulchre de Conde, B., Bihoreau, M. T., Shaver, C., Dufier, J. L., Marsac, C., Lathrop, M., Menasche, M., and Abitbol, M. M., 2000, Homozygous deletion in the coding sequence of the c-mer gene in RCS rats unravels general mechanisms of physiological cell adhesion and apoptosis. Neurobiol. Dis. 7:586–599.
Nandrot, E. F., Kim, Y., Brodie, S. E., Huang, X., Sheppard, D., and Finnemann, S. C., 2004, Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking αvβ5 integrin. J. Exp. Med. 200:1539–1545.
Parsons, J. T., 2003, Focal adhesion kinase: the first ten years. J. Cell Sci. 116:1409–1416.
Ryeom, S. W., Sparrow, J. R., and Silverstein, R. L., 1996, CD36 participates in the phagocytosis of rod outer segments by retinal pigment epithelium. J. Cell Sci. 109:387–395.
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Finnemann, S.C., Nandrot, E.F. (2006). Mertk Activation During RPE Phagocytosis in Vivo Requires αVβ5 Integrin. In: Hollyfield, J.G., Anderson, R.E., LaVail, M.M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 572. Springer, Boston, MA. https://doi.org/10.1007/0-387-32442-9_69
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DOI: https://doi.org/10.1007/0-387-32442-9_69
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