Abstract
Diurnal phagocytosis of shed photoreceptor outer segments (POS) by the underlying retinal pigment epithelium (RPE) is essential for vision. RPE receptor proteins identified thus far to play a role in recognition and engulfment of POS include the integrin receptor αvβ5, the tyrosine kinase MerTK, and the scavenger receptor CD36. These receptors have in common that they also contribute to phagocytosis of apoptotic cells by other phagocytic cell types. Tissue transglutaminase 2 (TG2) is a multifunctional enzyme with several functions in the cytoplasm and as a component of the extracellular matrix. Complex formation of extracellular TG2 with αvβ3 integrin receptors facilitates phagocytosis of apoptotic cells by macrophages. Here, we investigated whether TG2 also plays a role in diurnal POS phagocytosis by RPE cells that depends on αvβ5 integrin, which is closely related to αvβ3. To this end, we examined retinal morphology and RPE phagocytic activity in TG2 knockout (TG2−/−) mice. TG2−/− retinas showed no obvious abnormalities in mice of 2 or 12 months of age. Furthermore, quantification of numbers of POS phagosomes in the RPE in situ at different times of day revealed a robust peak of phagosomes in TG2 null RPE at 1 h after light onset but minimal phagosomes 8 h later. Thus, RPE cells lacking TG2 phagocytose POS in a diurnal rhythm like wild-type RPE cells and unlike RPE cells lacking αvβ5 integrin. These data indicate that TG2 is not required for RPE-mediated phagocytosis of shed POS.
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Acknowledgments
These studies were supported by NIH grant EY-13295 to S.C.F. and Hungarian Research Fund OTKA 77587 to Z.S.
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Ruggiero, L., Sarang, Z., Szondy, Z., Finnemann, S.C. (2012). αvβ5 Integrin-Dependent Diurnal Phagocytosis of Shed Photoreceptor Outer Segments by RPE Cells Is Independent of the Integrin Coreceptor Transglutaminase-2. In: LaVail, M., Ash, J., Anderson, R., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 723. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0631-0_93
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DOI: https://doi.org/10.1007/978-1-4614-0631-0_93
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