Why Does the Presence of Neovascular Macular Degeneration Correlate with Increased Cancer Risk?
Researchers have discovered many correlations between age-related diseases that occur in very different tissues at opposite ends of the body and, at first glance, appear to have little to do with one another. These correlations arise because the many varied outcomes of aging emerge from a much smaller set of underlying mechanisms of damage, such as mitochondrial dysfunction and accumulation of senescent cells. The patterned burden of these these forms of damage, amount and distribution in the body, will tend to favor the emergence of some forms of age-related disease over others. Regardless of how this all progresses, these underlying forms of damage are the real target that should be addressed by potential therapies to treat aging.
Age-related macular degeneration (AMD) is one of the leading causes of irreversible vision loss among the elderly in industrialized countries. Neovascular AMD (nAMD), characterized by choroidal neovascularization, represents the most vision-threatening form of AMD and is uniquely dependent on vascular endothelial growth factor (VEGF)-driven angiogenesis. While the ocular consequences of nAMD are well-established, mounting evidence suggests potential links between AMD and systemic diseases, including cancer. AMD and cancer may share several common risk factors and biological mechanisms, such as advanced age, smoking, oxidative stress, chronic inflammation, and dysregulated angiogenic pathways, notably involving VEGF.
Beyond angiogenesis, nAMD may also reflect broader systemic aging biology. Increasing evidence suggests that nAMD is associated with processes such as chronic low-grade inflammation ("inflammaging"), immune dysregulation, and extracellular matrix remodeling. Cellular senescence, while an important component of aging, has been suggested to play dual roles: tumor-suppressive early via growth arrest, but tumor-promoting later through the senescence-associated secretory phenotype (SASP). In the context of AMD, several studies have demonstrated involvement of senescent retinal pigment epithelial cells and their SASP signatures.
These mechanistic lines of evidence provide a framework in which nAMD might not only share angiogenic pathways with cancer but also intersect with systemic aging processes, potentially helping to explain its selective associations with certain malignancies. Recent genome-wide studies have revealed that both AMD and various cancer types exhibit polygenic susceptibility involving complement activation, lipid metabolism, and extracellular matrix regulation-pathways that are also implicated in tumor microenvironments and cancer progression-raising the possibility that such systemic vulnerability could extend beyond the eye.