RT Journal Article
T1 AMD-Like Substrate Causes Epithelial Mesenchymal Transition in iPSC-Derived Retinal Pigment Epithelial Cells Wild Type but Not C3-Knockout.
A1 Chinchilla Rodríguez, Blanca
A1 Fernandez Godino, Rosario
AB The Bruch’s membrane (BrM) is a five-layered extracellular matrix (ECM) that supports the retinal pigment epithelium (RPE). Normal age-related changes in the BrM may lead to RPE cell damage and ultimately to the onset and progression of age-related macular degeneration (AMD), which is the most common cause of visual loss among the elderly. A role for the complement system in AMD pathology has been established, but the disease mechanisms are poorly understood, which hampers the design of efficient therapies to treat millions of patients. In an effort to identify the mechanisms that lead from normal aging to pathology, we have developed a cell-based model using complement deficient human induced pluripotent stem cell (iPSC)-derived RPE cells cultured on an AMD-like ECM that mimics BrM. The data present evidence that changes in the ECM result in loss of differentiation and promote epithelial mesenchymal transition (EMT) of healthy RPE cells. This pathological process is mediated by complement activation and involves the formation of a randomly oriented collagen meshwork that drives the dedifferentiation of the RPE monolayer. Genetic ablation of complement component 3 has a protective effect against EMT but does not prevent the abnormal deposition of collagens. These findings offer new insights into the sequence of events that initiate AMD and may guide the design of efficient therapies to treat this disease with unmet medical needs.
PB MDPI
SN 1661-6596
YR 2021
FD 2021-07-30
LK https://hdl.handle.net/20.500.14352/116707
UL https://hdl.handle.net/20.500.14352/116707
LA eng
NO Chinchilla, B., & Fernandez-Godino, R. (2021). AMD-like substrate causes epithelial mesenchymal transition in iPSC-derived retinal pigment epithelial cells wild type but not C3-knockout. International Journal of Molecular Sciences, 22(15). https://doi.org/10.3390/IJMS22158183
NO Author Contributions: B.C. carried out the experiments and revised the final manuscript. R.F.-G. raised the funds, conceived the presented idea, planned, and helped to carry out the experiments,supervised the work and wrote the manuscript. All authors have read and agreed to the published version of the manuscript.
NO The Association for Research in Vision and Ophthalmology-
NO Harvard Medical School
NO Harvard Medical School, Boston, USA
DS Docta Complutense
RD 22 abr 2025