Abstract:Age-related macular degeneration (AMD) is a leading cause of blindness and is becoming a global crisis since affected people will increase to 288 million by 2040. Genetics, age, diabetes, gender, obesity, hypertension, race, hyperopia, iris-color, smoking, sun-light and pyroptosis have varying roles in AMD, but oxidative stress-induced inflammation remains a significant driver of pathobiology. Eye is a unique organ as it contains a remarkable oxygen-gradient that generates reactive oxygen species (ROS) which upregulates inflammatory pathways. ROS becomes a source of functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells and retinal ganglion cells. Reports demonstrated that hydrogen sulfide (H2S) acts as a signaling molecule and that it may treat ailments. Therefore, we propose a novel hypothesis that H2S may restore homeostasis in the eyes thereby reducing damage caused by oxidative injury and inflammation. Since H2S has been shown to be a powerful antioxidant because of its free-radicals’ inhibition properties in addition to its beneficial effects in age-related conditions, therefore, patients may benefit from H2S salubrious effects not only by minimizing their oxidant and inflammatory injuries to retina but also by lowering retinal glutamate excitotoxicity.