Department of Ophthalmology and Visual Science, Yale University, New Haven, CT, USA.
Department of Surgery, Yale University, New Haven, CT, USA.
Stem Cells Transl Med. 2022 Mar 31;11(3):269-281. doi: 10.1093/stcltm/szac001.
Retinal pigment epithelium (RPE) cells grown on a scaffold, an RPE patch, have potential to ameliorate visual impairment in a limited number of retinal degenerative conditions. This tissue-replacement therapy is suited for age-related macular degeneration (AMD), and related diseases. RPE cells must be transplanted before the disease reaches a point of no return, represented by the loss of photoreceptors. Photoreceptors are specialized, terminally differentiated neurosensory cells that must interact with RPE's apical processes to be functional. Human photoreceptors are not known to regenerate. On the RPE's basal side, the RPE transplant must induce the reformation of the choriocapillaris, thereby re-establishing the outer blood-retinal barrier. Because the scaffold is positioned between the RPE and choriocapillaris, it should ideally degrade and be replaced by the natural extracellular matrix that separates these tissues. Besides biodegradable, the scaffolds need to be nontoxic, thin enough to not affect the focal length of the eye, strong enough to survive the transplant procedure, yet flexible enough to conform to the curvature of the retina. The challenge is patients with progressing AMD treasure their remaining vision and fear that a risky surgical procedure will further degrade their vision. Accordingly, clinical trials only treat eyes with severe impairment that have few photoreceptors to interact with the transplanted patch. Although safety has been demonstrated, the cell-replacement mechanism and efficacy remain difficult to validate. This review covers the structure of the retina, the pathology of AMD, the limitations of cell therapy approaches, and the recent progress in developing retinal therapies using biomaterials.
视网膜色素上皮 (RPE) 细胞在支架上生长形成的 RPE 贴片，具有改善少数视网膜退行性疾病导致的视力损害的潜力。这种组织替代疗法适用于年龄相关性黄斑变性 (AMD) 及相关疾病。RPE 细胞必须在疾病发展到无法挽回的地步（即感光细胞丧失）之前进行移植。感光细胞是专门的、终末分化的神经感觉细胞，必须与 RPE 的顶端突起相互作用才能发挥功能。已知人类感光细胞不能再生。在 RPE 的基底侧，RPE 移植必须诱导脉络膜毛细血管的重新形成，从而重建外层血视网膜屏障。由于支架位于 RPE 和脉络膜毛细血管之间，因此它应该理想地降解并被分隔这些组织的天然细胞外基质所取代。除了可生物降解外，支架还需要无毒、足够薄以不影响眼睛的焦距、足够强以在移植过程中存活，并且足够灵活以适应视网膜的曲率。挑战在于进展性 AMD 患者珍惜他们剩余的视力，并且担心有风险的手术会进一步损害他们的视力。因此，临床试验仅治疗严重受损且与移植贴片相互作用的感光细胞较少的眼睛。尽管已经证明了安全性，但细胞替代机制和疗效仍然难以验证。本文综述了视网膜的结构、AMD 的病理学、细胞治疗方法的局限性，以及使用生物材料开发视网膜治疗方法的最新进展。
