Retbindin mediates light-damage in mouse retina while its absence leads to premature retinal aging.
Retbindin mediates light-damage in mouse retina while its absence leads to premature retinal aging.
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DOI：
10.1016/j.exer.2021.108698
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发表时间：
2021-08
影响因子：
3.4
通讯作者：
Wistow G
中科院分区：
文献类型：
--
作者：
Fan J;Rajapakse D;Peterson K;Lerner J;Parsa S;Ponduri A;Sagar V;Duncan T;Dong L;Wistow G
视觉需要色素 11-顺式视黄醛（视网膜）在视网膜色素上皮 (RPE) 和光感受器之间的运输和回收。 11-顺式视网膜也是暗适应小鼠眼中光介导的光感受器死亡所必需的，可能是通过过度刺激适应弱光的视杆细胞而实现的。 Retbindin 是一种光感受器特异性蛋白，其功能尚不清楚，位于 RPE 和光感受器尖端之间。出乎意料的是，具有retbindin靶向缺失（KO）的年轻Rtbdn-KO小鼠在漂白后表现出视网膜功能再生延迟，并且对光诱导的光感受器死亡有很强的抵抗力。此外，生物层干涉测量结合研究表明重组 retbindin 对类维生素A（尤其是 11-顺式视黄醛）具有显着的亲和力。这表明 retbindin 可能通过 11-cis 视黄醛转运介导光损伤。在 Rtbdn-KO 小鼠中，视网膜发育正常，视杆和视锥视网膜电图 (ERG) 振幅长达 4 个月，但隐式时间和 c 波受到影响。然而，随着年龄的增长，光适应和暗适应的 ERG 振幅均显着下降，光感受器外节变得紊乱。然而，与其他报道相反，视网膜变性或黄素水平下降很少。 RPE 形成空泡以及脂质、蛋白质和钙沉积物，让人想起与年龄相关的黄斑变性。过早衰老的其他迹象包括 OPN4+ 视网膜神经节细胞的丧失和小胶质细胞的激活。因此，retbindin 在哺乳动物视觉周期中发挥着意想不到的作用，可能是为了适应弱光下的视觉。它介导暗适应眼睛的光损伤，但也在光适应反应和长期视网膜稳态中发挥作用。
Vision requires the transport and recycling of the pigment 11-cis retinaldehyde (retinal) between the retinal pigment epithelium (RPE) and photoreceptors. 11-cis retinal is also required for light-mediated photoreceptor death in dark-adapted mouse eye, probably through overstimulation of rod cells adapted for low light. Retbindin is a photoreceptor-specific protein, of unclear function, that is localized between the RPE and the tips of the photoreceptors. Unexpectedly, young Rtbdn-KO mice, with targeted deletion (KO) of retbindin, showed delayed regeneration of retinal function after bleaching and were strongly resistant to light-induced photoreceptor death. Furthermore, bio-layer interferometry binding studies showed recombinant retbindin had significant affinity for retinoids, most notably 11-cis retinal. This suggests that retbindin mediates light damage, probably through a role in transport of 11-cis retinal. In Rtbdn-KO mice, retinal development was normal, as were amplitudes of rod and cone electroretinograms (ERG) up to 4 months, although implicit times and c-waves were affected. However, with aging, both light- and dark-adapted ERG amplitudes declined significantly and photoreceptor outer segments became disordered, However, in contrast to other reports, there was little retinal degeneration or drop in flavin levels. The RPE developed vacuoles and lipid, protein and calcium deposits reminiscent of age-related macular degeneration. Other signs of premature aging included loss of OPN4+ retinal ganglion cells and activation of microglia. Thus, retbindin plays an unexpected role in the mammalian visual cycle, probably as an adaptation for vision in dim light. It mediates light damage in the dark-adapted eye, but also plays a role in light-adapted responses and in long term retinal homeostasis.
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影响因子：
4.8
作者：
Ansari, Amir Mehdi;Ahmed, A. Karim;Matsangos, Aerielle E.;Lay, Frank;Born, Louis J.;Marti, Guy;Harmon, John W.;Sun, Zhaoli
通讯作者：
Sun, Zhaoli
DOI：
10.1097/opx.0000000000000322
发表时间：
2014-08
期刊：
Optometry and vision science : official publication of the American Academy of Optometry
影响因子：
--
作者：
Fletcher EL;Jobling AI;Greferath U;Mills SA;Waugh M;Ho T;de Iongh RU;Phipps JA;Vessey KA
通讯作者：
Vessey KA
影响因子：
4.8
作者：
Kelley, Ryan A.;Al-Ubaidi, Muayyad R.;Naash, Muna I.
通讯作者：
Naash, Muna I.
DOI：
10.1136/bjophthalmol-2011-300344
发表时间：
2011-12
期刊：
The British journal of ophthalmology
影响因子：
--
作者：
Curcio CA;Johnson M;Rudolf M;Huang JD
通讯作者：
Huang JD
影响因子：
--
作者：
Ma W;Wong WT
通讯作者：
Wong WT