Mitochondrial decay and impairment of antioxidant defenses in aging RPE cells.
In the eye, the retinal pigment epithelium (RPE) is exposed to a highly oxidative environment, partly due to elevated oxygen partial pressure from the choriocapillaris and to digestion of polyunsaturated fatty acid laden photoreceptor outer segments. Here we examined the vulnerability of RPE cells to stress and changes in their mitochondria with increased chronological aging and showed that there is greater sensitivity of the cells to oxidative stress, alterations in their mitochondrial number, size, shape, matrix density, cristae architecture, and membrane integrity as a function of age. These features correlate with reduced cellular levels of ATP, ROS, and [Ca(2+)](c), lower Deltapsim, increased [Ca(2+)](m) sequestration and decreased expression of mtHsp70, UCP2, and SOD3. Mitochondrial decay, bioenergetic deficiencies, and weakened antioxidant defenses in RPE cells occur as early as age 62. With increased severity, these conditions may significantly reduce RPE function in the retina and contribute to age related retinal anomalies.
Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA, USA. openji7127@hotmail.com
Yuan
Y
He
Joyce
J
Tombran-Tink
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000368:Aged; D000375:Aging / Q000187:drug effects / Q000473:pathology*; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D002648:Child; D005434:Flow Cytometry; D005452:Fluoresceins / Q000378:metabolism; D005453:Fluorescence; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D053141:Organelle Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*
C110400:2',7'-dichlorodihydrofluorescein diacetate; D000975:Antioxidants; D005452:Fluoresceins; D024101:Mitochondrial Proteins; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D002118:Calcium