Animal Models and New Approach Methodologies in Retinal Disease Research: A Comprehensive Review

Studies employing animal models play a pivotal role in advancing our understanding of the pathophysiology of retinal diseases. These models enable the investigation of molecular and cellular mechanisms underlying retinal structural damage, as well as the assessment of genetic and environmental factors contributing to disease development. The application of appropriate experimental models provides essential insights into the progression of degenerative processes and tissue responses to therapeutic interventions. The advancement of modern molecular biology and genetic engineering techniques has facilitated the development of increasingly precise animal models, which have proven crucial for identifying pathological alterations occurring in the course of retinal diseases. In recent years, research has demonstrated that, depending on the model employed, the observed changes may involve inflammatory processes, oxidative stress, photoreceptor dysfunction, extracellular matrix remodeling, and aberrant glial cell responses. It has also been shown that the nature and dynamics of these alterations vary according to the specific disease entity and the animal species used. The aim of this review is to compile and systematize current knowledge regarding the most commonly used animal models in retinal disease research and to discuss their utility in analyzing potential pathogenetic mechanisms and therapeutic targets. The review also highlights emerging complementary research strategies associated with New Approach Methodologies (NAMs), including retinal progenitor and iPSC-derived cell-based approaches, advanced retinal imaging techniques, and alternative experimental platforms such as the chorioallantoic membrane (CAM) assay, which may support translational retinal research and reduce reliance on traditional animal models. The authors hope that this work will contribute to the refinement of preclinical research methodologies and, through an improved understanding of the processes underlying the development of retinal diseases, facilitate the advancement of more effective diagnostic and therapeutic strategies in the future.