Abstract
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 [Ca2+]c, lower Δψm, increased [Ca2+]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.
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Acknowledgments
This work was supported by grants from the Ben Franklin Foundation, PA, USA, the National Basic Research Program of China (No. 2007CB512200), and the National Natural Science Foundation of China (No.30672275, No.30400486), NEI Core Grant P30 EY01931 (PI, Janice M Burke), and by an unrestricted grant from Research to Prevent Blindness, Inc. to the Medical College of Wisconsin. The first author received support from the China Scholarship Council.
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He, Y., Tombran-Tink, J. (2010). Mitochondrial Decay and Impairment of Antioxidant Defenses in Aging RPE Cells. In: Anderson, R., Hollyfield, J., LaVail, M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 664. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1399-9_20
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