Molins Blanca, Rodríguez Andrea, Llorenç Víctor, Adán Alfredo
Group of Ocular Inflammation: Clinical and Experimental Studies, Institut d'Investigacions Biomèdiques Agustí Pi I Sunyer (IDIBAPS), Barcelona, Spain.
Institut Clínic d'Oftalmologia (ICOF), Hospital Clínic Barcelona, Spain.
Neural Regen Res. 2024 Dec 1;19(12):2626-2636. doi: 10.4103/NRR.NRR-D-23-01789. Epub 2024 Mar 1.
Age-related macular degeneration, a multifactorial inflammatory degenerative retinal disease, ranks as the leading cause of blindness in the elderly. Strikingly, there is a scarcity of curative therapies, especially for the atrophic advanced form of age-related macular degeneration, likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier, the prime target tissue of age-related macular degeneration. Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier, integrated by the dynamic interaction of the retinal pigment epithelium, the Bruch's membrane, and the underlying choriocapillaris. The Bruch's membrane provides structural and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier, and therefore adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrier. In the last years, advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials. This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healthy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems. Then, we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling, discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.
年龄相关性黄斑变性是一种多因素炎症性视网膜退行性疾病，是老年人失明的主要原因。令人惊讶的是，治愈性疗法匮乏，尤其是对于萎缩性晚期年龄相关性黄斑变性，这可能是由于缺乏能够完全重现外血视网膜屏障天然结构的模型，而外血视网膜屏障是年龄相关性黄斑变性的主要靶组织。标准的体外系统依赖于二维单培养，无法充分再现外血视网膜屏障的结构和功能，外血视网膜屏障由视网膜色素上皮、布鲁赫膜和下方的脉络膜毛细血管的动态相互作用整合而成。布鲁赫膜提供结构和机械支持，并调节外血视网膜屏障中的分子运输，因此，合适的布鲁赫膜模拟物是开发外血视网膜屏障生理相关模型的关键。近年来，生物材料工程领域的进展提供了从多种材料模拟布鲁赫膜的新方法。本综述讨论了健康和年龄相关性黄斑变性状态下外血视网膜屏障成分的综合特性和功能，以了解充分制造布鲁赫膜仿生系统的要求。然后，我们讨论了用于年龄相关性黄斑变性体外建模的制造布鲁赫膜样支架的新型材料和技术，讨论了它们的优点和挑战，并特别关注基于脱细胞组织的布鲁赫膜样模拟物的潜力。
