December 2015
Volume 56, Issue 13
Research Highlight  |   December 2015
Photoreceptor Mitochondrial Reserve Capacity: Is It the Etiology for Differential Compartmental Vulnerability?
Author Affiliations
  • Donald A. Fox
    College of Optometry University of Houston, Houston, Texas, United States;
  • Elda M. Rueda
    College of Optometry University of Houston, Houston, Texas, United States;
Investigative Ophthalmology & Visual Science December 2015, Vol.56, 8437. doi:
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      Donald A. Fox, Elda M. Rueda; Photoreceptor Mitochondrial Reserve Capacity: Is It the Etiology for Differential Compartmental Vulnerability?. Invest. Ophthalmol. Vis. Sci. 2015;56(13):8437. doi:

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      © ARVO (1962-2015); The Authors (2016-present)

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The study of mitochondrial function/dysfunction and its relation to neurodegeneration requires standardized and sensitive techniques that enable the identification of molecular targets for cell type–specific neuroprotection. Using small central retinal punches from light-adapted wild-type and transgenic (Tg) C57BL/6J mice, Kooragayala et al.1 examined changes in the retinal oxygen consumption rate (OCR) from the Seahorse XF24 Bioanalyzer normalized to mitochondrial cytochrome a content. Maximal and high uncoupled OCRs in wild-type mice were achieved with Ames media or glucose plus lactate, but not with mitochondrial-specific fuels. Using mitochondrial uncouplers with wild-type and Nrl−/− mice, they concluded that rod and cone photoreceptor (PR) mitochondria have a similar and limited mitochondrial reserve capacity (MRC) of 20% to 25%, albeit uncoupler-induced MRC in isolated rat retinal mitochondria is 82%.2 In contrast, Tg mice with dysfunctional or no PRs have lower OCRs, but higher MRCs: results attributed to the inner retina.1 They suggest the limited MRC in PR mitochondria serves as an early indicator of high metabolic stress, which increases vulnerability of PRs to energy challenges, oxidative stress, and degeneration. However, glucose use, lactate production [∼P], and/or oxygen consumption are not uniform in different retinal layers or among the four distinct PR mitochondrial compartments.3,4 For example, PR synaptic terminals have a higher [∼P], lower oxygen consumption, and increased vulnerability to toxicant-induced stress relative to inner segments.3,4 The current study1 advances the understanding of PR mitochondrial vulnerability and thereby emphasizes the importance of determining the MRC of different retinal cells and their compartments in other models of retinal disease. To further enhance the usefulness of this ex vivo technique, future studies might also determine the Pasteur and Crabtree effects; MRC of the different PR mitochondrial populations during pathophysiological conditions and development; and alternative strategies that PRs use to accommodate their cellular requirements for [∼P]. 
Kooragayala K, Gotoh N, Cogliati T, et al. Quantification of oxygen consumption in retina ex vivo demonstrates limited reserve capacity of photoreceptor mitochondria. Invest Ophthalmol Vis Sci. 2015; 56: 8428–8436.
Medrano CJ, Fox DA. Substrate-dependent effects of calcium on rat retinal mitochondrial respiration: physiological and toxicological studies. Toxicol Appl Pharmacol. 1994; 124: 309–321.
Matchinsky FM, Passonneau JV, Lowry OH. Quantitative histochemical analysis of glycolytic intermediates and cofactors with an oil well technique. J Histochem Cytochem. 1968; 16: 29–39.
Perkins GA, Scott R, Perez A, Ellisman MH, Johnson JE, Fox DA. Bcl-xL-mediated remodeling of rod and cone synaptic mitochondria after postnatal lead exposure: electron microscopy, tomography and oxygen consumption. Mol Vis. 2012; 18: 3029–3048.

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