Department of Biological Sciences, Center for Cancer, Genetic Diseases, and Gene Regulation, Fordham University, 441 East Fordham Road, Larkin Hall, 10458, Bronx, NY, USA,
Adv Exp Med Biol. 2014;801:91-6. doi: 10.1007/978-1-4614-3209-8_12.
In the mammalian retina, life-long renewal of rod photoreceptor outer segments involves circadian shedding of distal outer segment tips and their prompt phagocytosis by the adjacent retinal pigment epithelium (RPE) every morning after light onset. Failure of this process causes retinal dystrophy in animal models and its decline likely contributes to retinal aging and some forms of degeneration of the human retina. We previously found that surface exposure of the membrane phospholipid phosphatidylserine (PS) is restricted to outer segment tips with discrete boundaries in mouse retina and that both frequency and length of tips exposing PS peak after light onset. Here, we sought to test mechanisms photoreceptors use to restrict PS specifically to their outer segment tips. To this end, we tested whether nocodazole or cytochalasin D, perturbing microtubule or F-actin microfilament cytoskeleton, respectively, affect localization of externalized PS at outer segment tips. Fluorescence imaging of PS exposed by rods in freshly dissected, live mouse retina showed normal PS demarcation of outer segment tips regardless of drug treatment. These results suggest that the mechanism that restricts externalized PS to rod tips is independent of F-actin and microtubule cytoskeletal systems.
在哺乳动物的视网膜中，杆状光感受器外节的终身更新涉及到在每天早晨光照开始后，远端外节尖端的昼夜节律性脱落，并迅速被相邻的视网膜色素上皮（RPE）吞噬。如果这个过程失败，会导致动物模型中的视网膜营养不良，其衰退可能导致视网膜老化和人类视网膜的某些形式的退化。我们之前发现，在小鼠视网膜中，质膜磷脂酰丝氨酸（PS）的表面暴露仅限于具有离散边界的外节尖端，并且 PS 暴露的频率和长度在光照开始后达到峰值。在这里，我们试图测试光感受器用来将 PS 特异性限制在外节尖端的机制。为此，我们测试了长春花碱或细胞松弛素 D 是否分别扰乱微管或 F-肌动蛋白微丝细胞骨架，从而影响外节尖端暴露的 PS 的定位。在新鲜分离的活体小鼠视网膜中，对杆状细胞暴露的 PS 进行荧光成像显示，无论药物处理如何，外节尖端的 PS 边界均正常。这些结果表明，将外显 PS 限制在杆状细胞尖端的机制独立于 F-肌动蛋白和微管细胞骨架系统。
