Progressive Photoreceptor Dysfunction and Age-Related Macular Degeneration-Like Features in rp1l1 Mutant Zebrafish.
Progressive Photoreceptor Dysfunction and Age-Related Macular Degeneration-Like Features in rp1l1 Mutant Zebrafish.
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Rp1l1突变斑马鱼的进行性光感受器功能障碍和年龄相关性黄斑变性样特征。
DOI：
10.3390/cells9102214
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发表时间：
2020-09-30
期刊：
影响因子：
6
通讯作者：
Allison WT
中科院分区：
文献类型：
--
作者：
Noel NCL;Nadolski NJ;Hocking JC;MacDonald IM;Allison WT
光感受器疾病会导致无法弥补的视力丧失和失明，对生活质量产生巨大影响。RP 1 L1的致病性突变导致感光细胞变性，如隐匿性黄斑营养不良和视网膜色素变性。RP 1 L1是光感受器轴丝的组成部分，轴丝是光感受器感光外节的骨架结构。我们使用CRISPR/Cas9基因组编辑产生了rp 1 l1斑马鱼突变体。突变动物具有进行性光感受器功能缺陷，如通过电生理学评估所确定的。光学相干断层扫描显示光感受器层的间隙，破坏光感受器马赛克，和更薄的视网膜。突变型视网膜光感受器外节紊乱，光感受器和视网膜色素上皮细胞之间有富含脂质的视网膜下玻璃纤维样沉积。我们的突变体是RP 1 L1相关的感光细胞疾病的一种新模型，也是第一个视网膜下玻璃状核沉积的感光细胞变性的斑马鱼模型，这是年龄相关性黄斑变性的一个特征。
Photoreceptor disease results in irreparable vision loss and blindness, which has a dramatic impact on quality of life. Pathogenic mutations in RP1L1 lead to photoreceptor degenerations such as occult macular dystrophy and retinitis pigmentosa. RP1L1 is a component of the photoreceptor axoneme, the backbone structure of the photoreceptor’s light-sensing outer segment. We generated an rp1l1 zebrafish mutant using CRISPR/Cas9 genome editing. Mutant animals had progressive photoreceptor functional defects as determined by electrophysiological assessment. Optical coherence tomography showed gaps in the photoreceptor layer, disrupted photoreceptor mosaics, and thinner retinas. Mutant retinas had disorganized photoreceptor outer segments and lipid-rich subretinal drusenoid deposits between the photoreceptors and retinal pigment epithelium. Our mutant is a novel model of RP1L1-associated photoreceptor disease and the first zebrafish model of photoreceptor degeneration with reported subretinal drusenoid deposits, a feature of age-related macular degeneration.
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影响因子：
7.2
作者：
Bujakowska KM;Liu Q;Pierce EA
通讯作者：
Pierce EA
影响因子：
4.4
作者：
Aleman, Tomas S.;Cideciyan, Artur V.;Jacobson, Samuel G.
通讯作者：
Jacobson, Samuel G.
影响因子：
5.3
作者：
Liu, Q;Zuo, J;Pierce, EA
通讯作者：
Pierce, EA
影响因子：
5.2
作者：
Conte, I;Lestingi, M;Banfi, S
通讯作者：
Banfi, S
影响因子：
2.6
作者：
Doerre, G;Malicki, J
通讯作者：
Malicki, J