Abstract
Abstract: :
Purpose: Mitochondrial fission and fusion regulate energy and calcium levels, and are an early event in apoptosis. The purpose of this study was to determine whether photoreceptor mitochondria undergo fission and fusion in vivo. Methods: Male Sprague–Dawley rats were dark adapted and then stimulated with bright light for 1, 2, 3, 4, or 5 hours. Some retinas were examined immediately by electron microscopy; others were examined after 10 days by light and electron microscopy. Outer nuclear layer thicknesses were measured in vertical sections of entire retinas and compared to dark controls to determine percent of cell loss. Results: In healthy retinas there were 8 long peripheral mitochondria per ellipsoid in rat rod photoreceptors. These were straight, arranged peripherally, and up to 10 µm in length. After 5 hours of bright light, these mitochondria became rounded and increased in number (17 per outer segment in plane of section), and after 4 and 5 hours of light + 10 days, 11% and 54%, respectively, of photoreceptors were lost. Retinas examined 10 days after 1, 2, and 3 hours of light treatment did not lose photoreceptors, but their ellipsoid mitochondria rapidly rounded up and underwent fission within the stimulus interval; mitochondria undergoing fission were seen with 2–3 completely separated inner membrane–bound units surrounded by a single intact outer membrane. Finally, retinas examined 10 days after 2 hours of light exhibited long mitochondria. Conclusions: Bright light treatment initiates photoreceptor ellipsoid mitochondrial fission. If the light stimulus is of long enough duration, photoreceptor death occurs by apoptosis. However, if the light stimulus is of sub–threshold duration, mitochondrial fission is induced, but photoreceptors recover and ellipsoid mitochondria undergo fusion. The ellipsoid mitochondria are capable of altering their morphology, probably to best meet cell demands, by the processes of fission and fusion. When these demands cannot be met, cell death by apoptosis follows, suggesting that mitochondrial fission may be an early event in photoreceptor cell death. Supported by NIH EY05121; DARPA HR0011–04–C–0068.
Keywords: mitochondria • photoreceptors • apoptosis/cell death