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 2026

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. Dr. Huo’s recent publications demonstrated that choroidal endothelial to mesenchymal transition (EndMT) plays a vital role in the formation of subretinal fibrosis. 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 is to study whether and how glycolysis mediated by glycolytic genes induces EndMT induction, and the consequent subretinal fibrosis in AMD.

In 2026, Dr. Huo will conduct studies aiming to determine the role of GPR81 in PFKFB3-regulated EndMT. In addition, Dr. Huo’s lab will process the collected RPE/choroid complex for qRT-PCR and Western blots to examine the levels of EndMT-associated markers, including SNAIL1, ACTA2, FN, COL1, Vimentin, and modified histone, including acetylated histone and lactylated histone from samples collected in 2025.

Progress in 2025

Studies proposed in Aim 1a and Aim 2a were completed as planned. In Aim 1a, Dr. Huo found that the reduction of lactate production with siLDLA was able to reduce EndMT induction, evident with reduced expression of EndMT transcription factor SNAIL1, EndMT marker ACTA2, and EndMT molecules TAGLN, FN, COL1, examined with qRT PCR and Western blotting. In Aim 2a, samples for both male and female Pfkfb3indΔVEC mice and their control Pfkfb3indVEC mice post lazer-induced CNV and treatment were collected.