Chen Siyu, Li Minghui, Sun Jianguo, Wang Dan, Weng Chuanhuang, Zeng Yuxiao, Li Yijian, Huo Shujia, Huang Xiaona, Li Shiying, Zou Ting, Xu Haiwei
Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Key Lab of Visual Damage and Regeneration and Restoration of Chongqing, Chongqing, China.
Front Cell Dev Biol. 2022 Feb 10;10:801302. doi: 10.3389/fcell.2022.801302. eCollection 2022.
Radiation retinopathy (RR) is a common complication following radiation therapy of globe, head, and neck malignancies, and is characterized by microangiopathy, neuroretinopathy, and the irreversible loss of visual function. To date, there is no effective treatment for RR. Stem cells have been clinically used to treat retinal degeneration. CD133CD34 cells from human umbilical cord blood (-CD133CD34 cells), a subpopulation of hematopoietic stem cells, were applied to determine their protective efficacy on irradiated rat retinas. After X-ray irradiation on the retinas, rats were intravitreally injected with -CD133CD34 cells. Transplantation of -CD133CD34 cells prevented retinal dysfunction 2 weeks post-operation and lasted at least 8 weeks. CD133CD34 cells were distributed along the retinal vessel and migrated to the ganglion cell layer. Moreover, grafted CD133CD34 cells reduced the apoptosis of endothelial and ganglion cells in irradiated rats and increased the number of survived CD31 retinal endothelial cells and Brn3a ganglion cells at 2 and 4 weeks, respectively, post-operation. Co-culturing of CD133CD34 cells or supernatants with irradiated human retinal microvascular endothelial cells (hRECs) confirmed that CD133CD34 cells ameliorated hREC apoptosis caused by irradiation. Mechanistically, we found that angioprotective mediators and neurotrophic factors were secreted by CD133CD34 cells, which might attenuate irradiation-induced injury of retinal endothelial cells and ganglion cells. hUCB-CD133CD34 cell transplantation, as a novel treatment, protects retinal endothelial and ganglion cells of X-irradiated rat retinas, possibly through angioprotective and neurotrophic factors.
放射性视网膜病变（RR）是眼球、头部和颈部恶性肿瘤放射治疗后的常见并发症，其特征为微血管病变、神经视网膜病变以及视功能的不可逆丧失。迄今为止，RR尚无有效的治疗方法。干细胞已在临床上用于治疗视网膜变性。来自人脐带血的CD133CD34细胞（-CD133CD34细胞），即造血干细胞的一个亚群，被用于确定它们对受照射大鼠视网膜的保护效果。在对视网膜进行X射线照射后，给大鼠玻璃体内注射-CD133CD34细胞。-CD133CD34细胞移植在术后2周预防了视网膜功能障碍，且至少持续了8周。CD133CD34细胞沿视网膜血管分布并迁移至神经节细胞层。此外，移植的CD133CD34细胞减少了受照射大鼠内皮细胞和神经节细胞的凋亡，并分别在术后2周和4周增加了存活的CD31视网膜内皮细胞和Brn3a神经节细胞的数量。将CD133CD34细胞或其上清液与受照射的人视网膜微血管内皮细胞（hRECs）共培养证实CD133CD34细胞改善了照射引起的hREC凋亡。从机制上讲，我们发现CD133CD34细胞分泌血管保护介质和神经营养因子，这可能减轻照射诱导的视网膜内皮细胞和神经节细胞损伤。hUCB-CD133CD34细胞移植作为一种新的治疗方法，可能通过血管保护和神经营养因子保护X射线照射大鼠视网膜的内皮细胞和神经节细胞。
