Rettinger Christina L, Wang Heuy-Ching
Ocular and Sensory Trauma Task Area, U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas, USA,
Ocular and Sensory Trauma Task Area, U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas, USA.
Cells Tissues Organs. 2018;206(3):119-132. doi: 10.1159/000497296. Epub 2019 Mar 15.
Retinal degenerative diseases such as macular degeneration, glaucoma, and diabetic retinopathy constitute the leading cause of blindness in the industrialized world. There is a continuous demand in investigative ophthalmic research for the development of new treatment modalities for retinal therapy. Unfortunately, efforts to identify novel neuroprotective and neuroregenerative agents have often been hindered by an experimental model gap that exists between high-throughput methods via dissociated cells and preclinical animal models. Even though dissociated cell culture is rapid and high-throughput, it is limited in its ability to reproduce the in vivo conditions. In contrast, preclinical animal models may offer greater fidelity, albeit they lack efficiency and experimental control. Retina explant cultures provide an ideal bridge to close this gap and have been used to study an array of biological processes such as retinal development and neurodegeneration. However, it is often difficult to interpret findings from these studies due to the wide variety of experimental species and culture methods used. This review provides a comprehensive overview of current ex vivo neuroretina culture methods and assessments, with a focus on their suitability, advantages, and disadvantages, along with novel insights and perspectives on the organotypic culture model as a high-throughput platform for screening promising molecules for retinal regeneration.
视网膜退行性疾病,如黄斑变性、青光眼和糖尿病性视网膜病变,是工业化国家失明的主要原因。眼科研究领域一直迫切需要开发新的视网膜治疗方法。不幸的是,通过解离细胞的高通量方法与临床前动物模型之间存在的实验模型差距,常常阻碍了新型神经保护和神经再生药物的研发。尽管解离细胞培养快速且高通量,但其再现体内条件的能力有限。相比之下,临床前动物模型可能具有更高的保真度,尽管它们缺乏效率和实验可控性。视网膜外植体培养为弥合这一差距提供了理想的桥梁,并已用于研究一系列生物学过程,如视网膜发育和神经退行性变。然而,由于所使用的实验物种和培养方法种类繁多,这些研究的结果往往难以解释。本综述全面概述了当前离体神经视网膜培养方法及其评估,重点关注其适用性、优点和缺点,以及关于器官型培养模型作为筛选有前景的视网膜再生分子的高通量平台的新见解和观点。