An Overview of Current Glaucomatous Trabecular Meshwork Models

AbstractPurpose To provide an overview of the existing alternative models for studying trabecular meshwork (TM).Methods Literature review.Results The TM is a complex tissue that regulates aqueous humor outflow from the eye. Dysfunction of the TM is a major contributor to the pathogenesis of open-angle glaucoma, a leading cause of irreversible blindness worldwide. The TM is a porous structure composed of trabecular meshwork cells (TMC) within a multi-layered extracellular matrix (ECM). Although dysregulation of the outflow throughout the TM represents the first step in the disease process, the underlying mechanisms of TM degeneration associate cell loss and accumulation of ECM, but remain incompletely understood, and drugs targeting the TM are limited. Therefore, experimental models of glaucomatous trabeculopathy are necessary for preclinical screening, to advance research on this disease's pathophysiology, and to develop new therapeutic strategies targeting the TM. Traditional animal models have been used extensively, albeit with inherent limitations, including ethical concerns and limited translatability to humans. Consequently, there has been an increasing focus on developing alternative in vitro models to study the TM. Recent advancements in three-dimensional cell culture and tissue engineering are still in their early stages and do not yet fully reflect the complexity of the outflow pathway. However, they have shown promise in reducing reliance on animal experimentation in certain aspects of glaucoma research.Conclusion This review provides an overview of the existing alternative models for studying TM and their potential for advancing research on the pathophysiology of open-angle glaucoma and developing new therapeutic strategies.Keywords: Glaucoma modeltrabecular meshwork3D culturein vitro modeltissue engineeringoutflow Author contributionC.B. encouraged J.B. to investigate the existing TM models and supervised the findings of this work. J.B. F.B.-B. and C.B. conducted extensive literature research. J.B. and F.B.-B. wrote the initial manuscript. A. L. and C.B. provided critical insights and expertise in the field, contributing to the interpretation of the findings and revision of the manuscript. C.B. contributed to the conceptualization and organization of the review. All authors reviewed and approved the submitted version.Disclosure statementNo potential conflict of interest was reported by the author(s).Additional informationFundingThe authors received no financial support for the research, authorship, or publication of this article.