提高移植光感受器功能性整合的策略
Strategies to improve functional integration of transplanted photoreceptors
王俊 1陈亦棋 2沈丽君2
作者信息
- 1. 浙江大学医学院附属第二医院眼科,杭州 310003
- 2. 浙江省人民医院眼科,杭州 310014
- 折叠
摘要
视网膜退行性疾病的最终结局是光感受器的大量丢失,造成视力不可逆的损害,目前基本上无有效治疗措施.光感受器移植为一种潜在的细胞治疗手段,旨在通过替换丢失的光感受器,重建视网膜回路,在一定程度上帮助恢复视网膜功能.然而,物质交换机制的发现揭示了既往研究结果中移植光感受器的整合比例低、外段形成不足及突触形成不够等问题,显示了该疗法临床转化的难度.本文通过多个维度综述了提高移植光感受器功能性整合的策略,探究相关内容的可行性,具体包括选择最佳发育时间窗的移植细胞群,增强与宿主视网膜间的相互作用;破坏宿主外界膜,减轻视网膜重塑,提高移植细胞的迁移及整合;利用免疫调节,减少小胶质细胞活化,改善宿主的移植微环境;通过视网膜片或生物支架的移植形式,提高移植光感受器的组织性;合理地开发及使用生物材料,优化移植细胞的生理微环境;充分评估手术参数,降低手术本身对移植细胞及宿主视网膜的影响.
Abstract
The final outcome of the retinal degenerative diseases is the massive loss of photoreceptors,resulting in irreversible visual impairment which lacks effective treatment at present.As a potential therapeutic approach,photoreceptor transplantation can be used to restore retinal function to a certain extent by replacing the lost photoreceptors and rebuilding the retinal circuits.However,the discovery of material exchange unveiled a number of problems in previous studies,including low cellular integration,insufficient outer segment and synapse formation,highlighting the challenges of clinical translation.To explore the possibility of increasing the functional integration of photoreceptors,this article reviewed a variety of strategies,including selection of the transplanted cells with optimal developmental stage to enhance the interaction with the host retina,disruption of the outer limiting membrane and alleviation of retinal remodeling to improve the migration and integration of the transplanted photoreceptors,regulation of immunity can be used to reduce microglial activation to create a better host microenvironment for transplantation,use of retinal sheets or biological scaffolds to improve photoreceptor organization,rational development and use of biomaterials to optimize the physiological microenvironment of the transplanted cells,adequate evaluation of surgical parameters to reduce the effect of surgery on the transplanted cells and the host retina.
关键词
视网膜退行性疾病/干细胞移植/细胞治疗/光感受器/再生医学Key words
Retinal degeneration/Stem cell transplantation/Cell therapy/Photoreceptor/Regenerative medicine引用本文复制引用
基金项目
国家重点研发计划(2022YFC2404305)
出版年
2024
NETL
NSTL
维普
万方数据