Complement Factor H in C. Elegans Model of AMD

Article: Study Identifies New Mechanism that May Cause Blindness in Older Adults
Source: University of Maryland School of Medicine, via NEI
Published: April 12, 2021

Photoreceptor (green) and inversin (red) proteins are
compartmentalized in healthy retinas (top), but overlap (yellow)
in mouse and human retinas with CFH mutations (bottom)

Researchers working with a laboratory model of C. elegans have found a potential new mechanism for age-related macular degeneration (AMD). Specifically, they looked at the contribution of protein complement factor H (CFH), after previous research showed that mutations related to it are seen in a large number of AMD patients. The role of complement factor H is to mark cells in the body as self to protect them from an immune attack. This link between CFH and AMD led some researchers to hypothesize that AMD is due to the immune system attacking the body's cells that were not marked as self. The researchers were curious to explore new mechanisms of the disease using nematode lab models. Roundworms in particular have a version of CFH in the middle of their antennas, specifically in the cilia, which are responsible for sensing the environment. The CFH proteins are located next to another important antenna protein called inversin. In roundworms bred to lack CFH, inversin is spread throughout the antennas rather than located in the middle. Roundworm antennas have some structural similarities to the photoreceptors of the human eye. For example, CFH and inversin have the same positioning in the cilia of photoreceptors in healthy human retinal tissue. However, in people with CFH mutations, inversin was spread around rather than located in neat bands. The authors state, "The role of CFH in cilia compartment boundaries is conserved in vertebrate photoreceptors, suggesting that structural defects in photoreceptor cilia make a contribution to AMD progression in patients with CFH mutations that has not been appreciated previously."

My rating of this study: ⭐

Acker N, Smith H, Devine C, et al. "A complement factor H homolog, heparan sulfation, and syndecan maintain inversin compartment boundaries in C. elegans cilia." PNAS.  118(16):e2016698118. April 2021. https://doi.org/10.1073/pnas.2016698118