Experimental models for keratoconus: Insights and challenges

Keratoconus, a progressive corneal disorder characterized by the thinning and conical protrusion of the cornea because of collagen degradation, poses significant challenges to both clinicians and researchers. Most successful animal models of keratoconus are based on genetic mutations and knock-outs in mice and rats that hinder normal corneal stromal architecture, thickness, or strength. While mice and rat models are suitable to study the molecular mechanism and physiological changes to the cornea, they are not suitable for experimental research; especially for surgical interventions like: deep anterior lamellar keratoplasty (DALK), stromal lenticule addition keratoplasty, and other advanced therapies. This review article comprehensively examines recent advancements in experimental models for keratoconus, focusing on their potential for translational research and the challenges ahead. It explores the historical context of experimental models, focusing on animal-based models, mainly rabbits in particular. These advancements enable researchers to mimic the biomechanical and biochemical alterations observed in keratoconic corneas. While these models offer valuable insights into disease mechanisms and treatment development, several challenges remain in transforming experimental findings into clinical applications.