Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 91735, Iran.
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Int J Mol Sci. 2021 Feb 10;22(4):1776. doi: 10.3390/ijms22041776.
Progenitor cells derived from the retinal pigment epithelium (RPECs) have shown promise as therapeutic approaches to degenerative retinal disorders including diabetic retinopathy, age-related macular degeneration and Stargardt disease. However, the degeneration of Bruch's membrane (BM), the natural substrate for the RPE, has been identified as one of the major limitations for utilizing RPECs. This degeneration leads to decreased support, survival and integration of the transplanted RPECs. It has been proposed that the generation of organized structures of nanofibers, in an attempt to mimic the natural retinal extracellular matrix (ECM) and its unique characteristics, could be utilized to overcome these limitations. Furthermore, nanoparticles could be incorporated to provide a platform for improved drug delivery and sustained release of molecules over several months to years. In addition, the incorporation of tissue-specific genes and stem cells into the nanostructures increased the stability and enhanced transfection efficiency of gene/drug to the posterior segment of the eye. This review discusses available drug delivery systems and combination therapies together with challenges associated with each approach. As the last step, we discuss the application of nanofibrous scaffolds for the implantation of RPE progenitor cells with the aim to enhance cell adhesion and support a functionally polarized RPE monolayer.
视网膜色素上皮细胞（RPECs）衍生的祖细胞已被证明是治疗退行性视网膜疾病的有前途的方法，包括糖尿病性视网膜病变、年龄相关性黄斑变性和 Stargardt 病。然而，Bruch 膜（BM）的退化已被确定为利用 RPECs 的主要限制因素之一。这种退化导致移植的 RPECs 的支持、存活和整合减少。有人提出，生成有组织的纳米纤维结构，试图模拟天然的视网膜细胞外基质（ECM）及其独特特性，可以用来克服这些限制。此外，可以掺入纳米颗粒为药物提供一个平台，以改善药物输送并在数月至数年内持续释放分子。此外，将组织特异性基因和干细胞掺入纳米结构中增加了基因/药物向眼后段的稳定性和转染效率。本综述讨论了现有的药物输送系统和联合治疗方法，以及每种方法相关的挑战。最后，我们讨论了纳米纤维支架在植入 RPE 祖细胞中的应用，目的是增强细胞黏附并支持功能极化的 RPE 单层。
