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Replenishment of TCA cycle intermediates provides photoreceptor resilience against neurodegeneration during progression of retinitis pigmentosa
Ashley A. Rowe, Pinkal D. Patel, Ruth Gordillo, Katherine J. Wert
Ashley A. Rowe, Pinkal D. Patel, Ruth Gordillo, Katherine J. Wert
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Research Article Metabolism Ophthalmology

Replenishment of TCA cycle intermediates provides photoreceptor resilience against neurodegeneration during progression of retinitis pigmentosa

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Abstract

The metabolic environment is important for neuronal cells, such as photoreceptors. When photoreceptors undergo degeneration, as occurs during retinitis pigmentosa (RP), patients have progressive loss of vision that proceeds to full blindness. Currently, there are no available treatments for the majority of RP diseases. We performed metabolic profiling of the neural retina in a preclinical model of RP and found that TCA cycle intermediates were reduced during disease. We then determined that (a) promoting citrate production within the TCA cycle in retinal neurons during disease progression protected the photoreceptors from cell death and prolonged visual function, (b) supplementation with single metabolites within the TCA cycle provided this therapeutic effect in vivo over time, and (c) this therapeutic effect was not specific to a particular genetic mutation but had broad applicability for patients with RP and other retinal degenerative diseases. Overall, targeting TCA cycle activity in the neural retina promoted photoreceptor survival and visual function during neurodegenerative disease.

Authors

Ashley A. Rowe, Pinkal D. Patel, Ruth Gordillo, Katherine J. Wert

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Usage data is cumulative from February 2025 through February 2026.

Usage JCI PMC
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PDF 143 27
Figure 490 9
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Citation downloads 151 0
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