Photoreceptor Degeneration: More Than a Bystander in Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of visual impairment affecting nearly 200 million people worldwide, and this number is expected to increase in the coming decades. The role of the retinal pigment epithelium (RPE) in AMD pathogenesis has been extensively studied. However, the contribution of photoreceptor (PR) dysfunction to AMD pathogenesis remains understudied and is a critical gap in our knowledge. The RPE and PRs are coupled to promote and enhance their respective survival and function, and this delicate relationship becomes disrupted in AMD. Furthermore, PR metabolic demands are postulated to contribute to AMD pathogenesis, their dysfunction is associated with both the early and end stages of AMD, and their death is central to the vision loss patient's experience in AMD. Here, we review clinical and basic science data indicating that PRs are likely more than a bystander in AMD and play a significant role in AMD pathogenesis.