Animal Models in Eye Research: Focus on Corneal Pathologies

Abstract

The eye is a complex sensory organ that enables visual perception of the world. The dysfunction of any of these tissues can impair vision. Conduction studies on laboratory animals are essential to ensure the safety of therapeutic products directly applied or injected into the eye to treat ocular diseases before eventually proceeding to clinical trials. Among these tissues, the cornea has unique homeostatic and regenerative mechanisms for maintaining transparency and refraction of external light, which are essential for vision. However, being the outermost tissue of the eye and directly exposed to the external environment, the cornea is particularly susceptible to injury and diseases. This review highlights the evidence for selecting appropriate animals to better understand and treat corneal diseases, which rank as the fifth leading cause of blindness worldwide. The development of reliable and human-relevant animal models is, therefore, a valuable research tool for understanding and translating fundamental mechanistic findings, as well as for assessing therapeutic potential in humans. First, this review emphasizes the unique characteristics of animal models used in ocular research. Subsequently, it discusses current animal models associated with human corneal pathologies, their utility in understanding ocular disease mechanisms, and their role as translational models for patients.

Keywords: animal models; cornea; corneal diseases; ocular research; translational research.

Figure 7

New approaches of cell-based therapy for corneal endothelial cell transplantation. Adapted from [230]. Copyright (2021), Elsevier, Experimental Eye Research.

Figure 1

Relative comparison of eyeball size and morphology between different species used in eye research.

Figure 2

Structure of the human ocular surface. (A) The human cornea is composed of five distinct layers, three of which are cellular (epithelium, stroma, and endothelium) and two acellular (Bowman’s and Descemet’s membranes). (B) Tear film organization consists of a mucin-gel layer adjacent to the corneal epithelial surface, an aqueous layer containing mucins and other soluble proteins, and a thin lipid film on the outer surface.

Figure 3

The two main enteropathogenic classifications of dry eye.

Figure 4

Suggested steps to assess tear film and ocular surface in animal models of dry eye.

Figure 5

Major differences in mucin production by (a) conjunctival epithelial cells, (b) corneal epithelial cells, and (c) conjunctival goblet cells, and in amino acid-dependent lengths of membrane-associated mucins (MUC1/Muc1, MUC4/Muc4, and MUC16/Muc16) between (A) the human and (B) the mouse ocular surface.

Figure 6

The mitotic capacity of corneal endothelial cells varies depending on the species. The regenerative ability of the human corneal endothelium is consistent with cat and nonhuman primate models. Reproduced from [209]. Copyright (2021), Annals of Translational Medicine.