Department of Ophthalmology

Baylor College of Medicine

Houston, TX

BASIC RESEARCH PROJECT

AMD and subretinal fibrosis

Research Interests

Dr. Huo is interested in developing new molecular strategies to limit subretinal fibrosis in Age-related Macular Degeneration (AMD). Glycolytic genes, including 6 phosphofructo-2-kinase/ fructose-2, 6-bisphosphatase isoform 3 (PFKFB3) are expressed in choroidal endothelial cells and contribute to their transitions to mesenchymal cells (EndMT).

Many of Dr. Huo’s research results on AMD (including angiogenesis and fibrosis) have been published in high-profile journals. Recently, two research projects were published in Science Translational Medicine, and  studies of those projects were also highlighted by the National Eye Institute/NIH (First Article, Second Article .

Plans for 2025

This proposal is designed to use genetically deficient cells and mice models to investigate the effect of glycolytic genes in subretinal fibrosis and to provide the basis for using inhibition of glycolysis as a novel approach to treating blinding retinal disease. Subretinal fibrosis is an end-stage fibrous plaque/disciform scar that progresses from choroidal neovascularization (CNV) of neovascular age-related macular degeneration (nAMD). It compromises highly organized anatomical layers and tightly coordinated cellular interactions, inevitably leading to irreversible visual impairment. Current treatment for subretinal fibrosis is limited; thus, therapeutic strategies for inhibiting subretinal fibrosis are imperative. Multiple cell types, including endothelial cells (ECs), have been proposed or demonstrated to participate in the formation of subretinal fibrosis.

Our recent publications demonstrated that choroidal endothelial to mesenchymal transition (EndMT) plays a vital role in the formation of subretinal fibrosis. Our preliminary data show that high levels of glycolytic enzymes, including PFKFB3 (6-phosphofructo-2 kinase/ fructose-2, 6-bisphosphatase isoform 3, Pfkfb3 gene for mice), were detected in RPE/choroid complex of mice with AMD, and the area of subretinal fibrosis was markedly decreased in Pfkfb3-/+ mice with AMD. Thus, the purpose of this project will study whether and how glycolysis mediated by glycolytic genes induces EndMT induction, and the consequent subretinal fibrosis in AMD.