Neuroprotective effects of bone marrow Sca-1(+) cells against age-related retinal degeneration in OPTN E50K mice.
Neuroprotective effects of bone marrow Sca-1(+) cells against age-related retinal degeneration in OPTN E50K mice.
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骨髓 Sca-1 细胞对 OPTN E50K 小鼠年龄相关性视网膜变性的神经保护作用
DOI：
10.1038/s41419-021-03851-0
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发表时间：
2021-06-15
影响因子：
9
通讯作者：
Yuan H
中科院分区：
文献类型：
--
作者：
Liu X;Hou M;Zhang S;Zhao Y;Wang Q;Jiang M;Du M;Shao Z;Yuan H
青光眼的特征是视网膜神经节细胞(RGC)死亡，其潜在机制仍很大程度上是未知的。视神经磷酸酶(OPTN)基因的E50K突变是导致正常眼压性青光眼(NTG)的主要原因，在没有高眼压的情况下，NTG会直接影响RGC，并会导致患者出现严重的青光眼症状。已证实骨髓干细胞通过其营养作用和归巢能力在衰老和疾病期间再生受损组织中发挥关键作用。在这里，我们将骨髓干细胞分离成Sca-1+和Sca-1-细胞，并将它们移植到致死照射的老年OPTN E50K小鼠体内，分别产生Sca-1+和Sca-1−嵌合体。在骨髓再生3个月后，我们研究了携带OPTN E50K突变的NTG模型小鼠的SCA-1+细胞是否最大限度地促进了视网膜的再生。我们发现，OPTN E50K突变加剧了NTG发育过程中视网膜和BM中与年龄相关的神经营养因子的缺乏，导致视网膜变性和BM功能障碍。健康幼鼠Sca-1+细胞的旁分泌营养作用强于幼年OPTN E50K小鼠Sca-1−细胞和Sca-1+细胞。此外，Sca-1+嵌合体比Sca-1−嵌合体和未经处理的OPTN E50K小鼠表现出更好的视觉功能。Sca-1+细胞比Sca-1−细胞被招募用于修复受损的视网膜和逆转神经营养因子高表达导致的视觉损害。这些发现表明，来自健康年轻小鼠的SCA-1+细胞可能因为其出色的神经营养能力而表现出修复非酒精性视网膜病变的能力增强。
Glaucoma is characterized by retinal ganglion cell (RGC) death, the underlying mechanisms of which are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal-tension glaucoma (NTG), which directly affects RGCs in the absence of high intraocular pressure and causes severe glaucomatous symptoms in patients. Bone marrow (BM) stem cells have been demonstrated to play a key role in regenerating damaged tissue during ageing and disease through their trophic effects and homing capability. Here, we separated BM stem cells into Sca-1+ and Sca-1- cells and transplanted them into lethally irradiated aged OPTN E50K mice to generate Sca-1+ and Sca-1− chimaeras, respectively. After 3 months of BM repopulation, we investigated whether Sca-1+ cells maximized the regenerative effects in the retinas of NTG model mice with the OPTN E50K mutation. We found that the OPTN E50K mutation aggravated age-related deficiency of neurotrophic factors in both retinas and BM during NTG development, leading to retinal degeneration and BM dysfunction. Sca-1+ cells from young healthy mice had greater paracrine trophic effects than Sca-1− cells and Sca-1+ cells from young OPTN E50K mice. In addition, Sca-1+ chimaeras demonstrated better visual functions than Sca-1− chimaeras and untreated OPTN E50K mice. More Sca-1+ cells than Sca-1− cells were recruited to repair damaged retinas and reverse visual impairment in NTG resulting from high expression levels of neurotrophic factors. These findings indicated that the Sca-1+ cells from young, healthy mice may have exhibited an enhanced ability to repair retinal degeneration in NTG because of their excellent neurotrophic capability.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
3.7
作者：
Semo M;Gias C;Ahmado A;Sugano E;Allen AE;Lawrence JM;Tomita H;Coffey PJ;Vugler AA
通讯作者：
Vugler AA
影响因子：
17.8
作者：
De Moraes CG;Liebmann JM;Levin LA
通讯作者：
Levin LA
年轻的骨髓 Sca-1 细胞通过激活 FGF2 来保护老化的视网膜免受缺血再灌注损伤。
影响因子：
5.3
作者：
Shao Z;Wu J;Du G;Song H;Li SH;He S;Li J;Wu J;Weisel RD;Yuan H;Li RK
通讯作者：
Li RK
影响因子：
3.4
作者：
Jiang, Bo;Gao, Lin;Yuan, Huiping
通讯作者：
Yuan, Huiping