Age-related macular degeneration (AMD) is a multifactorial disease with a strong genetic component. That is, the inheritance of gene variants that appeared during human evolution and are relatively common in our population, trigger the pathological mechanisms that lead to AMD. Beguier et al. demonstrate that a common haplotype of chromosome 10q26, the main genetic risk factor for AMD, increases the expression of the a protease called HTRA1 in macrophages. They show that the increased expression of HTRA1 inhibits the elimination of macrophages from the normally immunosuppressive retinal environment, paving the way for chronic pathogenic inflammation. In our evolutionary past, the stronger inflammatory response associated with this 10q26 haplotype may have increased the survival to infectious diseases leading to its high frequency in our modern day populations. The image illustrates this link of common genetic haplotypes at the origin of highly heritable AMD: Charles Darwin in the company of macrophages looks at us from inside the eye.

For further details on this study "The 10q26 Risk Haplotype of Age-Related Macular Degeneration Aggravates Subretinal Inflammation by Impairing Monocyte Elimination", please click this link to read the complete paper published by Immunity Volume 53, Issue 2, 18 August 2020, Pages 429-441.e8