Abstract
Abstract: :
Purpose: Synaptic and nonsynaptic brain mitochondria have different respiratory activities and differential susceptibilities to oxidative stress and hypoxia. There are also two different mitochondrial populations in photoreceptors, but little is known about their physiologic significance and pathologic implications. The purpose of this study was to determine if the two photoreceptor mitochondrial types are differentially sensitive to light–induced oxidative stress. Methods: Male Sprague–Dawley rats were dark adapted and then stimulated with bright light for 5 or 7 hours. Retinas were examined immunohistochemically 11 hours after light onset to localize DNA polymerase γ and the glutamate transporter VGlut1. These retinas were also examined by electron microscopy and compared to dark controls. Conventional histological techniques were followed. Results: Electron microscopy revealed two morphologically different sets of photoreceptor mitochondria. Those within the ellipsoid, totaling 8, are up to 10 µm in length and 300 nm in diameter, and are arranged vertically about the periphery of the cell, while synaptic mitochondria occur singly near the synaptic ribbon and are about 1000 nm in diameter. The mitochondrial repair enzyme DNA polymerase γ peaks in retina 6 hours following 5 hours of light treatment (Western blot analysis, ARVO 2004). DNA polymerase γ immunolocalizes only at photoreceptor terminals at this time and only in superior central retina, as corroborated by colocalization of polymerase γ and the synaptic terminal marker VGlut1. However, at 4 hours following 7 hours of light treatment, polymerase γ also localizes in inner segments. Conclusions: There are two populations of photoreceptor mitochondria, ellipsoid and synaptic, which are physically and functionally separate. Bright light treatment induces mitochondrial damage, but the synaptic population contains polymerase γ at shorter stimulus times than the inner segments, suggesting a greater sensitivity of the synaptic form to oxidative stress. The inner segment does not label with polymerase γ unless the stimulus time is increased, implying that ellipsoid mitochondria are better able to deal with light–induced oxidative stress, possibly because the "high risk" environment of the inner segment possesses more robust protective mechanisms. This suggests that manipulation of existing repair processes may contribute to the rescue of photoreceptors in degenerative diseases. Supported by NIH EY05121; DARPA HR0011–04–C–0068
Keywords: oxidation/oxidative or free radical damage • mitochondria • photoreceptors