From cells to flow: bioengineering Schlemm’s canal endothelium as a novel therapy for glaucoma

Abstract

Introduction. Glaucoma is a progressive visual neuropathy that is often linked to elevated intraocular pressure. It is primarily brought on by a malfunction in the normal outflow of aqueous humour. Even while the majority of current treatments use medicine or surgery to lower intraocular pressure, they do not address the underlying biological cause, which is damage to the structures that control outflow. The Schlemm's canal endothelium, a specialized endothelium with properties halfway between the vascular and lymphatic systems, has been shown to play a crucial role in maintaining intraocular pressure homeostasis in recent years. Increased drainage resistance in glaucoma is directly caused by its malfunction. The purpose of the research is to analyze the Schlemm canal endothelial bioengineering using stem cells and its promise as a regenerative treatment approach for glaucoma. Materials and methods. Databases as PubMed, Scopus, Web of Science were used to conduct a narrative literature review. Included were reviews and experimental papers from the past 20 years on regenerative applications in glaucoma, three-dimensional culture models, "eye-on-a-chip" microfluidic systems, and stem cell differentiation into Schlemm's canal-like endothelial cells. Analysis was done on biomechanical characteristics, phenotypic markers, biological mechanisms, and reported functional outcomes. Results. According to research, mesenchymal stem cells and induced pluripotent stem cells can develop into Schlemm's canal-specific endothelial cells that exhibit distinctive markers and react to mechanical stress similarly to natural tissue. Their incorporation into microfluidic devices and threedimensional models has made it possible to improve outflow and partially recreate the drainage pathway. Real therapeutic promise has been suggested by experimental models that demonstrate a decrease in drainage resistance and a return to normal intraocular pressure. There are still restrictions on tissue integration, immune response regulation, and long-term survival, though. Conclusion. A promising approach to regenerative therapy for glaucoma is the bioengineering of the Schlemm canal endothelium, which aims to restore the drainage pathway's physiological function rather than merely reduce intraocular pressure symptoms. Preclinical findings are promising, but more research is required to confirm safety and clinical suitability.