综述
ENGLISH ABSTRACT
RPE组织工程复合体中人造Bruch膜的生物材料研究进展
魏莺
马翔 [综述]
作者及单位信息
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DOI: 10.3760/cma.j.cn115989-20220510-00204
Progress in biomaterials of artificial Bruch membrane in RPE tissue engineering complex
Wei Ying
Ma Xiang
Authors Info & Affiliations
Wei Ying
Department of Ophthalmology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
Ma Xiang
Department of Ophthalmology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
·
DOI: 10.3760/cma.j.cn115989-20220510-00204
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摘要

退行性视网膜疾病如年龄相关性黄斑变性(AMD)可致永久性视力丧失。虽然抗血管内皮生长因子(anti-VEGF)和类固醇注射可有效治疗湿性AMD早期病变,但干性AMD及晚期地图样萎缩仍缺乏治疗方法。视网膜色素上皮(RPE)对维护视功能至关重要,其功能障碍与视网膜退行性疾病相关,行RPE移植可替换病变细胞保证RPE的正常功能,维持视网膜稳态。然而,研究显示单纯细胞注射的短期结果难以维持。成功的细胞移植治疗须同时改进功能异常的RPE细胞和细胞外微环境,生物材料支架的研发成为关键突破点。组织工程学为修复视网膜损伤并恢复其功能的提供了前景。功能性RPE单层移植需重塑极化RPE的紧密排列,组织工程化可实现RPE在生物材料支架——人造Bruch膜上的生长。联合支架培养使细胞生长和可移植性表现更佳。本文回顾了支持RPE培养的人造Bruch膜材料学研究现状,列举了典型案例,总结了RPE支架材料具体分类、机械及生物学特性,为开发新型材料、促进人造Bruch膜的RPE移植临床应用奠定基础。

视网膜变性;支架;生物材料;视网膜色素上皮;移植
ABSTRACT

Degenerative retinal diseases such as age-related macular degeneration (AMD) may cause permanent visual loss.Although anti-vascular endothelial growth factor (anti-VEGF) and steroid injection can effectively treat early lesions of wet AMD, there is still a lack of treatment for dry AMD and late geographic atrophy.Retinal pigment epithelium (RPE) is essential to maintain visual function, and its dysfunction is associated with retinal degenerative diseases.RPE transplantation can replace the diseased cells to ensure the normal function of RPE and maintain retinal homeostasis.However, studies have shown that the short-term results of cell injection alone are difficult to maintain.Successful cell transplantation therapy must simultaneously improve the dysfunctional RPE cells and extracellular microenvironment, and the research and development of biomaterial scaffolds has become a key breakthrough.Tissue engineering offers a prospect for repairing retinal damage and restoring its function.Functional RPE monolayer transplantation needs to remodel the tight arrangement of polarized RPE, and tissue engineering can realize the growth of RPE on the biomaterial scaffold artificial Bruch membrane.Combined with scaffold culture, cell growth and transplantability can be better.This paper reviews the research status of artificial Bruch membrane materials supporting RPE culture, lists typical cases, and summarizes the specific classification, mechanical and biological characteristics of RPE scaffold materials to lay the foundation for developing new materials and promoting the clinical application of artificial Bruch membrane in RPE transplantation.

Retinal degeneration;Scaffolds;Biomaterials;Retinal Pigment Epithelium;Transplantation
Ma Xiang, Email: mocdef.aabnis.piv7649amx
引用本文

魏莺,马翔. RPE组织工程复合体中人造Bruch膜的生物材料研究进展[J]. 中华实验眼科杂志,2025,43(03):276-282.

DOI:10.3760/cma.j.cn115989-20220510-00204

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视网膜退行性疾病如年龄相关性黄斑变性(age-related macular degeneration,AMD),是世界范围内50岁以上人群不可逆性视力丧失的首要原因,占世界盲人口的9.7%。尽管视网膜变性致病因素复杂,但最终病理过程常包括视网膜色素上皮(retinal pigment epithelium,RPE)和脉络膜组织的丢失。RPE位于视网膜外层,为六边形单层细胞,在吸收光线,异构化视黄醇,吞噬光损伤感光细胞外段,分泌生长因子,形成血-视网膜屏障等视功能的维持中起重要作用 [ 1 ]。Bruch膜为厚2~6 μm细胞外基质,由脉络膜毛细血管基底膜、外胶原层、弹性蛋白层、内胶原层和RPE基底层组成,可以支持RPE细胞粘附,并作为渗透性分子筛,在视网膜与脉络膜毛细血管物质交换中发挥作用 [ 2 ]。若RPE和Bruch膜丢失或损伤,可导致感光细胞功能障碍和不可逆性盲。
目前,RPE变性的治疗方法有限。尽管玻璃体内抗血管内皮生长因子(anti-vascular endothelial growth factor,anti-VEGF)和类固醇注射可有效治疗湿性AMD早期阶段,但目前尚无确切的干性AMD或视网膜晚期地图样萎缩的治疗方法。动物和临床研究均证实RPE细胞置换具有修复受损RPE层的潜力 [ 3 , 4 , 5 ]。尽管与其他技术相比,细胞悬液注射操作更简单快速且侵入性更小,但结果往往出现以下缺陷:细胞悬液回流玻璃体腔、RPE细胞粘附有限、Bruch膜老化、基底紊乱以及无法形成均一单层结构等 [ 6 ]。研究表明悬浮液、薄片或贴剂递送均不成功,RPE细胞必须重新附着在支架上才能确保移植后的长期存活 [ 7 ]。组织工程学已成为修复视网膜受损并恢复其功能的有前景的方法。
人造Bruch膜支撑的RPE细胞单层移植的优势在于细胞以高分化状态植入后可立即发挥生物活性,比悬浮液中细胞更易保留其上皮表型 [ 7 ],还可使RPE单层精确定位在视网膜下腔,防止单层折叠和起皱,提高细胞长期存活率,并使移植物更有效地整合和发挥功能。因此,相关RPE载体材料的开发是支持RPE单层功能完整的Bruch膜替代品发展的关键 [ 8 ]。此类支架材料除应便于手术操作外,还必须具备高孔隙率、大孔径及较薄尺寸,以确保证其扩散率和生物相容性,且细胞粘附。其次,材料还必须能够促进RPE的相关功能表达,如紧密连接、细胞极化、感光细胞外部片段的吞噬作用和规则的上皮单层 [ 9 ]。本综述拟介绍用于人造Bruch膜支架的天然材料、合成材料和两者的混合材料,简要概述人造Bruch膜支架材料的研究进展,并探讨相关运用的限制条件。
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马翔,Email: mocdef.aabnis.piv7649amx
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所有作者均声明不存在利益冲突
C
国家自然科学基金 (81271022)
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