Proline metabolism and transport in retinal health and disease.

Autor: Du J; Department of Ophthalmology and Visual Sciences, West Virginia University, Morgantown, WV, 26506, USA. jianhai.du@hsc.wvu.edu.; Department of Biochemistry, West Virginia University, Morgantown, WV, 26506, USA. jianhai.du@hsc.wvu.edu.; One Medical Center Dr, WVU Eye Institute, PO Box 9193, Morgantown, WV, 26505, USA. jianhai.du@hsc.wvu.edu., Zhu S; Department of Ophthalmology and Visual Sciences, West Virginia University, Morgantown, WV, 26506, USA.; Department of Biochemistry, West Virginia University, Morgantown, WV, 26506, USA., Lim RR; Department of Ophthalmology, University of Washington, Seattle, WA, 98109, USA., Chao JR; Department of Ophthalmology, University of Washington, Seattle, WA, 98109, USA.
Jazyk: angličtina
Zdroj: Amino acids [Amino Acids] 2021 Dec; Vol. 53 (12), pp. 1789-1806. Date of Electronic Publication: 2021 Apr 19.
DOI: 10.1007/s00726-021-02981-1
Abstrakt: The retina is one of the most energy-demanding tissues in the human body. Photoreceptors in the outer retina rely on nutrient support from the neighboring retinal pigment epithelium (RPE), a monolayer of epithelial cells that separate the retina and choroidal blood supply. RPE dysfunction or cell death can result in photoreceptor degeneration, leading to blindness in retinal degenerative diseases including some inherited retinal degenerations and age-related macular degeneration (AMD). In addition to having ready access to rich nutrients from blood, the RPE is also supplied with lactate from adjacent photoreceptors. Moreover, RPE can phagocytose lipid-rich outer segments for degradation and recycling on a daily basis. Recent studies show RPE cells prefer proline as a major metabolic substrate, and they are highly enriched for the proline transporter, SLC6A20. In contrast, dysfunctional or poorly differentiated RPE fails to utilize proline. RPE uses proline to fuel mitochondrial metabolism, synthesize amino acids, build the extracellular matrix, fight against oxidative stress, and sustain differentiation. Remarkably, the neural retina rarely imports proline directly, but it uptakes and utilizes intermediates and amino acids derived from proline catabolism in the RPE. Mutations of genes in proline metabolism are associated with retinal degenerative diseases, and proline supplementation is reported to improve RPE-initiated vision loss. This review will cover proline metabolism in RPE and highlight the importance of proline transport and utilization in maintaining retinal metabolism and health.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
Databáze: MEDLINE
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