Emerging Roles of Regulated Cell Death-mediated Inflammation in Pathophysiology of Ocular Diseases

Regulated cell death pathways are vital for proper developmental and homeostatic processes. Dysregulation of these pathways contributes to the pathogenesis of many diseases, including ocular inflammatory and neurodegenerative diseases such as glaucoma, diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and ocular surface diseases. Our knowledge of the regulated cell death pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis, has been extensively expanded in the recent years. The targeting of these pathways as a potential therapy for various ocular diseases is now widely recognized. In recent years, it has also become clear that in many circumstances, the engagement of multiple regulated cell death pathways could be coordinated through specific cross talks to drive a stress-specific cell death and disease pathogenesis. This knowledge is extended to the recognition that targeting multiple regulated cell death pathways could be more effective for the treatment of various pathologies. However, the identity of upstream regulatory pathways and the engagement hierarchy of individual pathways and their coordinated interactions require further investigation. Here, I will briefly introduce these regulated cell death processes, discuss the key regulatory pathways involved in determining cell death or survival, as well as upstream modulators. I will also highlight studies targeting these pathways as potential treatment strategies for various eye diseases.