Prominin-1缺失的爪蟾会出现视网膜下类风湿沉积、锥杆营养不良和 RPE 萎缩。

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Journal of cell science Pub Date : 2024-11-01 Epub Date: 2024-11-12 DOI:10.1242/jcs.262298
Brittany J Carr, Dominic Skitsko, Linnea M Kriese, Jun Song, Zixuan Li, Myeong Jin Ju, Orson L Moritz
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引用次数: 0

摘要

PROMININ-1(PROM1)突变与遗传性非综合症性视力丧失有关。我们利用CRISPR/Cas9技术诱导章鱼prom1基因突变,然后跟踪6周龄到3岁龄期视网膜疾病的进展。与 Prom1 基因缺失相关的蛙视网膜变性是年龄依赖性的,涉及光感受器变性之前的 RPE 功能障碍。在光感受器变性发生之前,老化的 Prom1 缺失蛙视网膜下间隙和外节段层的细胞碎片沉积物的大小和数量不断增加,其位置、组织学以及在彩色眼底摄影和光学相干断层扫描(OCT)中的表现与视网膜下类核素沉积物(SDD)相似。这些沉积物来源于 RPE 的证据包括沉积物中色素颗粒的浸润、OCT 测定的 RPE 变薄以及组织学和 OCT 测定的 RPE 紊乱。在我们的动物模型中,SDD 类沉积物的出现和积累以及 RPE 的变薄和紊乱表明,prom1 基因缺失介导的失明的潜在疾病机制是光感受器变性之前 RPE 的死亡和功能障碍,而不是像以前假设的那样直接影响光感受器外节的形态发生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
prominin-1-null Xenopus laevis develop subretinal drusenoid-like deposits, cone-rod dystrophy and RPE atrophy.

Prominin-1 (PROM1) variants are associated with inherited, non-syndromic vision loss. We used CRISPR/Cas9 to induce prom1-null mutations in Xenopus laevis and then tracked retinal disease progression from the ages of 6 weeks to 3 years. We found that prom1-null-associated retinal degeneration in frogs was age-dependent and involved retinal pigment epithelium (RPE) dysfunction preceding photoreceptor degeneration. Before photoreceptor degeneration occurred, aging prom1-null frogs developed larger and increasing numbers of cellular debris deposits in the subretinal space and outer segment layer, which resembled subretinal drusenoid deposits (SDDs) in their location, histology and representation as seen by color fundus photography and optical coherence tomography (OCT). Evidence for an RPE origin of these deposits included infiltration of pigment granules into the deposits, thinning of the RPE as measured by OCT, and RPE disorganization as measured by histology and OCT. The appearance and accumulation of SDD-like deposits and RPE thinning and disorganization in our animal model suggests an underlying disease mechanism for prom1-null-mediated blindness that involves death and dysfunction of the RPE preceding photoreceptor degeneration, instead of direct effects upon photoreceptor outer segment morphogenesis, as was previously hypothesized.

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来源期刊
Journal of cell science
Journal of cell science 生物-细胞生物学
CiteScore
7.30
自引率
2.50%
发文量
393
审稿时长
1.4 months
期刊介绍: Journal of Cell Science publishes cutting-edge science, encompassing all aspects of cell biology.
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