Diving deep into AMD, Yale researchers pinpoint cell types drug developers should pay special attention to
The wild successes of drugs like Eylea and Lucentis sometimes overshadow the fact that there still isn’t a cure for age-related macular degeneration, the leading cause of blindness among the elderly, especially the earlier-stage disease known as dry AMD. While around three dozen genes tied to the disease have been identified — giving rise to experimental gene therapies — some scientists believe a closer look is needed to figure out where exactly these genetic alterations are taking place.
In a new paper published in Nature Communications, a group of Yale researchers reported that macroglia, microglia, vascular cells, and cone photoreceptors are the main cell types associated with the risk of AMD.
Through performing parallel single-cell RNA sequencing on 20,901 cells retrieved from postmortem human retinas, they were able to construct a single-cell transcriptomic atlas of the eye tissue.
How is this significant? From the paper:
It was previously thought that AMD was due to pathology of the photoreceptors and retinal pigment epithelium. While our results demonstrate that the genetic risk variants contributing to AMD affect cone photoreceptors, they are associated with additional cell types, highlighting the importance of glial and vascular cells in disease pathogenesis. […] our data predicts that these cell types preferentially contribute to the pathogenesis of AMD, and provide genetic context to target these cell types for the development of new disease therapies.
By pinpointing cell types that are responsible for the deterioration, scientists can investigate new targets leading to potentially new types of therapy, added Brian Hafler, co-senior author and assistant professor of ophthalmology and visual science and of pathology at Yale.
Each subpopulation of cells they identified appeared to be marked by higher expression of subtype-specific markers, including FOS, FTL and COL4A3. Other genes such as GAPDH and UBC were ubiquitously expressed, they noted.