NADPH oxidase plays a central role in cone cell death in retinitis pigmentosa.
NADPH oxidase plays a central role in cone cell death in retinitis pigmentosa.
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DOI：
10.1111/j.1471-4159.2009.06195.x
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发表时间：
2009-08
影响因子：
4.7
通讯作者：
Campochiaro PA
中科院分区：
文献类型：
--
作者：
Usui S;Oveson BC;Lee SY;Jo YJ;Yoshida T;Miki A;Miki K;Iwase T;Lu L;Campochiaro PA
色素性视网膜炎（RP）是一种杆状光感受器因多种突变而死亡的疾病。视杆细胞死亡后，视网膜外的组织氧水平升高，视锥细胞出现渐进性氧化损伤，最终引发细胞凋亡。在这项研究中，我们研究了NADPH氧化酶和/或黄嘌呤氧化酶在增加组织氧和产生过量活性氧（导致球果氧化损伤）之间起关键中介作用的假设。在RP视网膜变性-1 （rd1+/+）模型中，NADPH氧化酶阻滞剂罗布宁，而黄嘌呤氧化酶阻滞剂别嘌呤醇，显著降低了氢乙胺在视网膜外的超氧自由基。用ELISA法测定羰基加合物对视网膜的氧化损伤程度，与对照剂处理的rd1+/+小鼠相比，用罗布麻素处理的小鼠，而不用别嘌呤醇处理的小鼠明显减少。罗布麻素处理的rd1+/+小鼠的视锥细胞密度保持不变，m-和s-视锥蛋白mRNA水平升高，平均光性b波振幅增加。在Q344ter小鼠（一种表达突变视紫红质的显性RP模型）中，与对照组相比，罗布草碱处理保留了视网膜电图b波振幅。这些数据表明，NADPH氧化酶，而不是黄嘌呤氧化酶，在RP中氧化应激导致锥体细胞死亡的产生中起关键作用，抑制NADPH氧化酶提供了一种新的治疗策略。
Retinitis pigmentosa (RP) is a collection of diseases in which rod photoreceptors die from a variety of mutations. After rods die, the level of tissue oxygen in the outer retina becomes elevated and there is progressive oxidative damage to cones that ultimately triggers apoptosis. In this study, we investigated the hypothesis that NADPH oxidase and/or xanthine oxidase serve as critical intermediaries between increased tissue oxygen and the generation of excessive reactive oxygen species that cause oxidative damage to cones. Apocynin, a blocker of NADPH oxidase, but not allopurinol, a blocker of xanthine oxidase, markedly reduced the superoxide radicals visualized by hydroethidine in the outer retina in the retinal degeneration-1 (rd1+/+) model of RP. Compared to rd1+/+ mice treated with vehicle, those treated with apocynin, but not those treated with allopurinol, had significantly less oxidative damage in the retina measured by ELISA for carbonyl adducts. Apocynin-treated, but not allopurinol-treated, rd1+/+ mice had preservation of cone cell density, increased mRNA levels for m- and s-cone opsin, and increased mean photopic b-wave amplitude. In Q344ter mice, a model of dominant RP in which mutant rhodopsin is expressed, apocynin treatment preserved photopic electroretinogram b-wave amplitude compared to vehicle-treated controls. These data indicate that NADPH oxidase, but not xanthine oxidase, plays a critical role in generation of the oxidative stress that leads to cone cell death in RP and inhibition of NADPH oxidase provides a new treatment strategy.
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影响因子：
5.6
作者：
Komeima, Keiichi;Rogers, Brian S.;Campochiaro, Peter A.
通讯作者：
Campochiaro, Peter A.
影响因子：
4.4
作者：
Natoli, Riccardo;Provis, Jan;Stone, Jonathan
通讯作者：
Stone, Jonathan
影响因子：
7.4
作者：
Komeima, Keiichi;Usui, Shinichi;Campochiaro, Peter A.
通讯作者：
Campochiaro, Peter A.
DOI：
10.1016/s0022-2828(85)80017-1
发表时间：
1985-01-01
影响因子：
5
作者：
CHAMBERS, DE;PARKS, DA;DOWNEY, JM
通讯作者：
DOWNEY, JM
影响因子：
6.6
作者：
Lu L;Oveson BC;Jo YJ;Lauer TW;Usui S;Komeima K;Xie B;Campochiaro PA
通讯作者：
Campochiaro PA