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rd10 鼠进行性视网膜变性的性别相关差异。

Sex-related differences in the progressive retinal degeneration of the rd10 mouse.

机构信息

Department of Biomedical Science, College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.

Department of Biology, College of Science, Florida Atlantic University, Boca Raton, FL, USA.

出版信息

Exp Eye Res. 2019 Oct;187:107773. doi: 10.1016/j.exer.2019.107773. Epub 2019 Aug 22.

Abstract

The retinal degeneration 10 (rd10) mouse is a model of autosomal recessive retinitis pigmentosa (RP), a disease that causes blindness through the progressive loss of photoreceptors. This study shows evidence of sex-related differences in RP onset and progression in rd10 retinas. The disease onset was considerably earlier in the female rd10 mice than in the male rd10 mice, as evidenced by a loss of PDE6β proteins and rod-dominated electroretinogram (ERG) responses at an early age. Single photopic flash and flicker ERG responses and immunolabeling of opsin molecules were analyzed in both genders to assess the sex differences in the degeneration of cones in the RP retinas. The averaged amplitudes of cone-mediated ERG responses obtained from the females were significantly smaller than the amplitudes of the responses from the age-matched males in the late stages of the RP, suggesting that cones might degenerate faster in the female retinas as the disease progressed. The rapid degeneration of cones caused a more substantial decrease in the ERG responses derived from the On-pathway than the Off-pathway in the females. In addition, the male rd10 mice had heavier body weights than their female counterparts aged between postnatal (P)18 and P50 days. In summary, female rd10 mice were more susceptible to retinal degeneration, suggesting that the female sex might be a risk factor for RP. The results have important implications for future studies exploring potential sex-related differences in RP development and progression in the clinic.

摘要

视网膜变性 10(rd10)小鼠是常染色体隐性视网膜色素变性(RP)的模型,这种疾病通过感光细胞的逐渐丧失导致失明。本研究表明 rd10 视网膜中存在与性别相关的 RP 发病和进展差异。与 rd10 雄性小鼠相比,雌性 rd10 小鼠的疾病发病明显更早,这表现为 PDE6β 蛋白的丧失以及在早期就出现 rod-dominated 视网膜电图(ERG)反应。在两种性别中都分析了单光闪光和闪烁 ERG 反应以及视蛋白分子的免疫标记,以评估 RP 视网膜中视锥细胞变性的性别差异。从女性获得的锥体细胞介导的 ERG 反应的平均幅度在 RP 的晚期明显小于同龄雄性的幅度,这表明随着疾病的进展,雌性视网膜中的视锥细胞可能更快地变性。由于雌性的锥体快速变性,在 ERG 反应中,On-pathway 的反应幅度比 Off-pathway 的反应幅度下降得更多。此外,雄性 rd10 小鼠在出生后(P)18 至 P50 天之间的体重比雌性重。总之,雌性 rd10 小鼠更容易发生视网膜变性,这表明女性性别可能是 RP 的一个危险因素。这些结果对于未来在临床上探索 RP 发展和进展中潜在的性别差异的研究具有重要意义。

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