title: Integrin αVβ5-mediated Removal of Apoptotic Cell Debris by the Eye Lens and Its Inhibition by UV Light Exposure.
abstract: Accumulation of apoptotic material is toxic and associated with cataract and other disease states. Identification of mechanisms that prevent accumulation of apoptotic debris is important for establishing the etiology of these diseases. The ocular lens is routinely assaulted by UV light that causes lens cell apoptosis and is associated with cataract formation. To date, no molecular mechanism for removal of toxic apoptotic debris has been identified in the lens. Vesicular debris within lens cells exposed to UV light has been observed raising speculation that lens cells themselves could act as phagocytes to remove toxic apoptotic debris. However, phagocytosis has not been confirmed as a function of the intact eye lens, and no mechanism for lens phagocytosis has been established. Here, we demonstrate that the eye lens is capable of phagocytizing extracellular lens cell debris. Using high throughput RNA sequencing and bioinformatics analysis, we establish that lens epithelial cells express members of the integrin αVβ5-mediated phagocytosis pathway and that internalized cell debris co-localizes with αVβ5 and with RAB7 and Rab-interacting lysosomal protein that are required for phagosome maturation and fusion with lysosomes. We demonstrate that the αVβ5 receptor is required for lens epithelial cell phagocytosis and that UV light treatment of lens epithelial cells results in damage to the αVβ5 receptor with concomitant loss of phagocytosis. These data suggest that loss of αVβ5-mediated phagocytosis by the eye lens could result in accumulation of toxic cell debris that could contribute to UV light-induced cataract formation.
authors.affiliation: From the Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida 33431.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chauss
authors.affiliation: From the Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida 33431.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Brennan
authors.affiliation: From the Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida 33431.
authors.forename: Olga
authors.initials: O
authors.lastname: Bakina
authors.affiliation: From the Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida 33431 mkantoro@health.fau.edu.
authors.forename: Marc
authors.initials: M
authors.lastname: Kantorow
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D030161:Avian Proteins / Q000378:metabolism*; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens; D004847:Epithelial Cells / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D010587:Phagocytosis / Q000528:radiation effects; D019030:Receptors, Vitronectin / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D030161:Avian Proteins; D005136:Eye Proteins; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D020691:rab GTP-Binding Proteins
keywords: UV light; apoptosis; cataract; cell survival; integrin; lens; phagocytosis