Mitochondria dynamics in the aged mice eye and the role in the RPE phagocytosis

Aging is a predominant risk factor for various eye diseases. Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and its etiology remains unclear. Fragmented and dysfunctional mitochondria are associated with age-related diseases. The retinal pigment epithelium (RPE), a polarized cell layer that functions in visual pigment recycling and degeneration, is suspected as the primary region site of AMD. In the present study, we investigated the relationship between mitochondrial dysfunction and RPE aging. Compared to young mice, aged pigmented mice (C57BL/6J, 12-month-old) exhibit decreased visual function without retinal thinning. Consistently, the rhodopsin expression level decreased in the outer segment of aged mice. Moreover, the cell volume of the RPE increased in aged animals. Interestingly, the expression of mitochondria dynamics-related proteins, including Drp1, was altered in the RPE-choroid complex but not in the neural retina after aging. Electron microscopy revealed that mitochondrial size decreased and cristae width increased in aged RPE. The photoreceptor outer segment (POS) treatment of ARPE-19 cells causes Drp1 activation. Furthermore, pharmacological suppression of mitochondrial fission improved the phagocytosis of the POS. These findings indicate that mitochondrial dysfunction and fission in RPE impede phagocytosis and cause retardation of the visual cycle, which can be one of the age-related defects in the retina that may contribute to the onset of AMD.