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D.R. Lopez–Osa, W.C. Gordon, M.S. Cortina, N.G. Bazan; Ellipsoid mitochondrial fission in light–induced photoreceptor apoptosis . Invest. Ophthalmol. Vis. Sci. 2004;45(13):780.
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Purpose: Photoreceptors have numerous long mitochondria in the ellipsoid, and large spherical mitochondria located near the synaptic ribbon. Differences in their metabolic rates in complexes I, II, III, IV, and V have been found suggesting that synaptic mitochondria are more susceptible to oxidative stress than non–synaptic forms. These mitochondria respond differentially to light. The mtDNA repair enzyme DNA polymerase γ is upregulated and selectively localized to synaptic mitochondria while ellipsoid mitochondria are spared. The purpose of this study was to define the response of retinal mitochondria to bright light. Methods: Sprague Dawley rats, dark adapted 2d, were light–treated for 3, 4, 5 or 7h and returned to darkness until killed at one hour intervals up to 8 hours. Control animals were maintained in darkness until sacrificed. Retinas were collected and processed for electron microscopy, immunohistochemistry and Western blot studies. Antibodies against DNA polymerase γ and Bax were used. Surface and volume measurements were obtained for both mitochondrial populations by electron microscopy. Results: Electron microscopy showed morphological differences in light treated ellipsoid mitochondria, compared to dark controls. At 0h after light treatment ellipsoid mitochondria appear fragmented and more numerous while synaptic mitochondria remain structurally unchanged. Western blot analysis demonstrated overexpression of Bax and upregulation of DNA polymerase γ at 6h. Immunohistochemistry for DNA polymerase γ showed selective localization of the enzyme to synaptic mitochondria. Only after the light stimulus was increased to 7h were the ellipsoid mitochondria labeled in a limited area of the retina. The calculated surface to volume ratios of dark control ellipsoid and synaptic mitochondria are 12.13 and 4.76 respectively. Conclusions: Ellipsoid and synaptic mitochondria respond differently to bright light. Oxidative stress–induced photoreceptor apoptosis involves ellipsoidal mitochondrial fission and upregulation of Bax, a proapoptotic molecule known to induce mitochondrial fragmentation, while upregulation of DNA polymerse γ occurs mainly to repair synaptic mtDNA. This evidence suggests a differential activity of synaptic and ellipsoid mitochondria during photoreceptor apoptosis.
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