Department of Neuroscience, Developmental and Regenerative Biology

University of Texas Health Science Center at San Antonio

San Antonio, TX

BASIC SCIENCE PROJECT

Modeling the role of 6-phosphofructo-2-kinase/fructose-2, 6 bisphosphatase 2 in retinal metabolism and retinal degenerative diseases

Research Interests

Photoreceptors are responsible for vision and depend on glycolysis, the metabolic process by which glucose is broken down by cells to produce energy, for the majority of their energy requirements. Disruptions in metabolic processes can lead to photoreceptor degeneration, worsening vision, and complete blindness. There is currently no treatment to reverse photoreceptor degeneration so it is imperative to understand and prevent the underlying processes that cause their degeneration. In retinal degenerative diseases (RDS), such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), the levels of metabolites in the retina are often dysregulated. However, the mechanisms and causes of metabolic dysregulation in RDS are poorly understood. For example, the enzyme 6-phosphofructo-2-kinase/fructose-2, 6 bisphosphatase 2 (PFKFB2) plays an important role in the regulation of glycolysis, yet it remains relatively unexamined in retinal disease. By using a mouse line with a mutation that models RP in humans (rd10 mice) we will study PFKFB2 and model metabolic dysregulation in RP. This work will help uncover possible treatments to metabolic dysregulation and thus prevent photoreceptor degeneration.

Previous research indicates that disruptions in glycolysis play an important role but are poorly understood in RP and other retinal diseases, such as AMD. Evidence suggests that dysregulation of PFKFB2, plays a role in the glycolytic disruptions in RP. Past work by Dr. Camacho has demonstrated the efficacy of modeling glycolysis in the photoreceptors. Using this work as a guide, this project will focus on modeling PFKFB2’s role in glycolysis during the development and progression of RP.

Plans in 2025

In 2025, the project seeks to improve the understanding of metabolic changes in RDS. Specifically, Dr. Camacho will model and investigate the expression and function of PFKFB2 in RP retinal metabolism using wild type and rd10 mice. This will allow us to examine and compare the metabolism of healthy and diseased mouse retinas throughout the development and progression of RP. Dr. Camacho hopes this will lay the groundwork for continued research and modeling into other enzymes or other RDS like AMD.

Specific Aims:
1. Generation and collection of experimental data on enzyme expression, metabolite concentration, and retinal structure and function from wild type and diseased retinas.
2. Creation of a mathematical model of retinal metabolism using the data collected.
3. In the long term, continue to refine the model with data from other enzymes and uncover possible treatments to reverse or prevent metabolic dysregulation in RDS.