氧化和内分泌网膜压力代表了胆固醇病的新型治疗标
Hajrah Sarkar1,2, Manuela Lahne1, Neelima Nair1
1UCL Institute of Ophthalmology, London EC1V 9EL, UK.
Antioxidants (Basel, Switzerland)
|September 28, 2023
概括
胆血症 (CHM) 是一种X关联的视网膜疾病,涉及由于REP1缺乏而导致的氧化和ER压力. 针对这些压力路径为这种情况提供了潜在的新疗法.
科学领域:
- 眼科医生 眼科 眼科
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- 胆固醇血症 (CHM) 是一种罕见的X相关胆固醇质变异,影响光受体,视网膜色素上皮 (RPE) 和胆固醇.
- 由CHM基因突变引起的CHM导致Rab护送蛋白1 (REP1) 缺乏,这对细胞内贩运至关重要.
- 目前,对于CHM没有批准的治疗方法,这凸显了对新型治疗策略的需求.
研究的目的:
- 调查氧化和内细胞网膜 (ER) 应激在CHM病变发生中的作用.
- 在CHM模型中选能够减轻这些压力路径的神经保护剂.
主要方法:
- 在CHM斑马鱼和患者衍生的纤维细胞中检查了氧化和ER压力标志物.
- 评估了与压力相关的关键基因的表达,包括txn,cat,sod3a,bip,atf4,atf6,SOD2和CHOP.
- 对神经保护剂进行了查,以确定它们在减少细胞压力的有效性.
主要成果:
- 在CHM斑马鱼中观察到氧化应激标记 (txn,cat,sod3a) 和ER应激标记 (bip,atf4,atf6) 的失调表达.
- 在CHM纤维细胞中,SOD2表达减少,BIP水平降低,CHOP表达增加.
- REP1 缺陷与膀运输受损,光受体外段细胞和黑色素体运输有关,导致视网膜和RPE压力.
结论:
- 氧化和ER压力与胆固醇病理生理学有关.
- 在REP1功能中的缺陷有助于视网膜和RPE中的细胞应激.
- 准氧化和ER压力路径为CHM提供了一个有前途的治疗方法.
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