Factor H-like Protein 1 Insufficiency in Retinal Pigment Epithelium

Principal Investigator


  • Jennifer  Chao, PhD

    Jennifer Chao, PhD


Project Goals

Early onset macular drusen (EOMD) is an inherited, severe form of AMD. We found that retinal pigmented epithelium (RPE) cells made from EOMD patients have decreased (~50%) expression of two important complement proteins, CFH and FHL-1. This significant decrease may alter local complement activity and RPE metabolism. We will study EOMD patient RPE, their gene-edited controls, and determine whether adding the FHL-1 gene back to the EOMD cells will help attenuate these pathogenic changes. This project will help our understanding of AMD disease pathogenesis and treatment.

Project Summary

We will culture induced pluripotent stem cell derived RPE cells from patients with a rare CFH variant that results in reduced CFH and FHL-1 protein production. In Aim 1, we will investigate the RPE extracellular complement activity and intracellular complosome. FHL-1 will be supplemented via AAV-mediated transduction to determine FHL-1 sufficiency to the local complement activity in the RPE. In Aim 2, we will evaluate if altered CFH and FHL-1 levels affects glucose metabolism and glycosaminoglycan synthesis in the RPE, and whether supplemental FHL-1 expression can attenuate these changes.


First published on: May 15, 2024

Last modified on: July 22, 2024