成纤维细胞生长因子21介导的视网膜神经胶质重塑在光感受器变性过程中维持视网膜功能。
Retinal glial remodeling by FGF21 preserves retinal function during photoreceptor degeneration.
作者信息
Fu Zhongjie, Qiu Chenxi, Cagnone Gael, Tomita Yohei, Huang Shuo, Cakir Bertan, Kotoda Yumi, Allen William, Bull Edward, Akula James D, Joyal Jean-Sébastien, Hellström Ann, Talukdar Saswata, Smith Lois E H
机构信息
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
The Manton Center for Orphan Disease, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
出版信息
iScience. 2021 Mar 29;24(4):102376. doi: 10.1016/j.isci.2021.102376. eCollection 2021 Apr 23.
The group of retinal degenerations, retinitis pigmentosa (RP), comprises more than 150 genetic abnormalities affecting photoreceptors. Finding degenerative pathways common to all genetic abnormalities may allow general treatment such as neuroprotection. Neuroprotection may include enhancing the function of cells that directly support photoreceptors, retinal pigment epithelial cells, and Müller glia. Treatment with fibroblast growth factor 21 (FGF21), a neuroprotectant, from postnatal week 4-10, during rod and cone loss in P23H mice (an RP model) with retinal degeneration, preserved photoreceptor function and normalized Müller glial cell morphology. Single-cell transcriptomics of retinal cells showed that FGF21 receptor was specifically expressed in Müller glia/astrocytes. Of all retinal cells, FGF21 predominantly affected genes in Müller glia/astrocytes with increased expression of axon development and synapse formation pathway genes. Therefore, enhancing retinal glial axon and synapse formation with neurons may preserve retinal function in RP and may suggest a general therapeutic approach for retinal degenerative diseases.
视网膜变性疾病组，即色素性视网膜炎（RP），包含150多种影响光感受器的基因异常。找到所有基因异常共有的退化途径可能会带来如神经保护等一般性治疗方法。神经保护可能包括增强直接支持光感受器、视网膜色素上皮细胞和穆勒胶质细胞的细胞功能。在视网膜变性的P23H小鼠（一种RP模型）中，从出生后第4周-10周，即在视杆和视锥细胞丧失期间，用神经保护剂成纤维细胞生长因子21（FGF21）进行治疗，可保留光感受器功能并使穆勒胶质细胞形态正常化。视网膜细胞的单细胞转录组学显示，FGF21受体在穆勒胶质细胞/星形胶质细胞中特异性表达。在所有视网膜细胞中，FGF21主要影响穆勒胶质细胞/星形胶质细胞中的基因，轴突发育和突触形成途径基因的表达增加。因此，增强视网膜胶质细胞与神经元之间的轴突和突触形成可能会保留RP患者的视网膜功能，并可能为视网膜退行性疾病提示一种一般性治疗方法。
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