AMD is a leading cause of vision loss in older adults. One of the main genetic risks associated with AMD is located on the Complement Factor H (CFH) gene, leading to an amino acid substitution in the Factor H (FH) protein (Y402H). However, the mechanism of how this FH variant promotes the onset of AMD remains unclear.
In their recent study, Dr. Angela Armento and Dr. Aparna Murali in the group of Prof. Marius Ueffing, established a novel co-culture model comprising CFH silenced RPE cells and porcine retinal explants derived from the visual streak of porcine eyes, which closely resembles the human macula. Previous work by Armento et al. had shown that FH deprivation in retinal pigment epithelial (RPE) cells, via CFH silencing, leads to increased inflammation, metabolic impairment and vulnerability toward oxidative stress. Employing their new model, the researchers could now show that CFH-deprived RPE cells, which display an AMD-like phenotype, cause retinal degeneration in co-cultured retinal explants.
The co-culture model is also suitable for human retinal explants. In a first experiment, the scientists observed a similar trend when RPE cells deprived of FH were co-cultured with human retinal explants from a single donor eye.
In summary, the study highlights the importance of RPE-derived Factor H for retinal homeostasis and provides a valuable model for AMD research, replicating the interplay of different retinal cell types.
Original Publication
Complement Factor H Loss in RPE Cells Causes Retinal Degeneration in a Human RPE-Porcine Retinal Explant Co-Culture Model.
Armento A, Murali A, Marzi J, Almansa-Garcia AC, Arango-Gonzalez B, Kilger E, Clark SJ, Schenke-Layland K, Ramlogan-Steel CA, Steel JC, Ueffing M. Biomolecules. 2021 Nov 3;11(11):1621.