Gasotransmitters in Glaucoma: A New Paradigm

Glaucoma, an ocular neurodegenerative condition, is the second leading cause of permanent loss of vision globally. It is characterized by progressive retinal ganglion cell (RCG) loss, optic nerve-head damage, irreversible visual field loss, and sometimes, increase in intraocular pressure (IOP). Existing therapeutic strategies target elevated IOP, the only modifiable risk factor for the disease, and fail to address the co-current neurodegeneration in the posterior segment of the eye. This demonstrates a huge gap in effective glaucoma therapy and highlights the need for multitargeting treatments that simultaneously reduce IOP in the anterior segment and mitigate neurodegeneration in the posterior segment of the eye. There is evidence that gasotransmitters such as nitric oxide (NO) and hydrogen sulfide (H₂S) could be beneficial in the treatment of glaucoma due to their ability to reduce IOP and mitigate neurodegeneration in the mammalian eye; while the second gasotransmitter, carbon monoxide (CO) can relax trabecular meshwork, enhance ocular perfusion and mitigate retinal neuronal apoptosis. Since current glaucoma therapies focus on IOP reduction, the multi-targeting nature of these gasotransmitters renders them as viable drug candidates to shift glaucoma therapy from IOP-targeting to multiple targeting therapeutic agents with improved patient outcomes. This review provides an overview of the "unmet" need in glaucoma therapy, summarizes current knowledge on the physiology of gasotransmitters and discusses their potential role as multitargeting therapeutic agents in glaucoma.