Looking for In Vitro Models for Retinal Diseases

Abstract

Retina is a layered structure of the eye, composed of different cellular components working together to produce a complex visual output. Because of its important role in visual function, retinal pathologies commonly represent the main causes of visual injury and blindness in the industrialized world. It is important to develop in vitro models of retinal diseases to use them in first screenings before translating in in vivo experiments and clinics. For this reason, it is important to develop bidimensional (2D) models that are more suitable for drug screening and toxicological studies and tridimensional (3D) models, which can replicate physiological conditions, for investigating pathological mechanisms leading to visual loss. This review provides an overview of the most common retinal diseases, relating to in vivo models, with a specific focus on alternative 2D and 3D in vitro models that can replicate the different cellular and matrix components of retinal layers, as well as injury insults that induce retinal disease and loss of the visual function.

Looking into the Eyes—In Vitro Models for Ocular Research

“…Currently, 2D cultures are the most common research models. The reason is that 2D cultures are relatively inexpensive, more modulable, and easy to maintain [ 118 ]. Because of reproducible results obtained in controlled conditions [ 119 ], big-scale screening assays should be performed on these models.…”

“…Because of reproducible results obtained in controlled conditions [ 119 ], big-scale screening assays should be performed on these models. The main weakness of 2D models is their low ability to recreate the complexity of different cell classes and matrices interaction [ 118 ]. On the other hand, 3D multilayer models seem to be sufficient for small-scale drug toxicity and irritation assays.…”

“…Moreover, 2D and 3D models seem to be limited in immunological disorders, such as allergy or sensitivity, because of their low of complexity. This problem could be addressed with organoids, which generate remarkable research outcomes, but only after long and arduous steps of standardization and testing [ 118 ].…”

Retinal Organoids and Retinal Prostheses: An Overview

“…For glaucoma, the most commonly used model is the ocular hypertension TDBA/2J mouse strain due to the spontaneous, age-related degeneration of retinal ganglion cells (RGCs). For diabetic retinopathy, genetic diabetes models are usually used, such as the Ins2Akita with a mutation in the insulin-2 gene or the ob/ob mice carrying a mutation in the leptin gene [ 42 , 45 ].…”

“…However, to test the efficiency of an inorganic or organic retinal prosthesis and to quantify stimulated retinal activity, most of the recent studies have based their investigations on animal models of RDs or animal in vitro explants ( Table 3 ). The retina in these models largely differ from the human retina and do not fully represent or recapitulate the human eye (patho)physiology [ 42 , 45 ]. Therefore, it is now of the utmost importance to use the potential of ROs, not only to investigate retinal disease mechanisms or gene- and cell-replacement therapies, but also as human in vitro models for retinal prosthesis optimization.…”