The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases

  • PNAS Nexus. 2023 Feb 3;2(3):pgad038. doi: 10.1093/pnasnexus/pgad038.
Ammaji Rajala  1  2 ,  Mohd A Bhat  1  2 ,  Kenneth Teel  1  2 ,  Gopa Kumar Gopinadhan Nair  1  2 ,  Lindsey Purcell  1  2 ,  Raju V S Rajala  1  2  3  4
Affiliations
  • 1. Department of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
  • 2. Dean McGee Eye Institute, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
  • 3. Department of Physiology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
  • 4. Department of Cell Biology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
PMID: 36896135 DOI: 10.1093/pnasnexus/pgad038
Abstract

The postmitotic retina is highly metabolic and the photoreceptors depend on aerobic glycolysis for an energy source and cellular anabolic activities. Lactate Dehydrogenase A (LDHA) is a key enzyme in aerobic glycolysis, which converts pyruvate to lactate. Here we show that cell-type-specific actively translating mRNA purification by translating ribosome affinity purification shows a predominant expression of LDHA in rods and cones and LDHB in the retinal pigment epithelium and Müller cells. We show that genetic ablation of LDHA in the retina resulted in diminished visual function, loss of structure, and a loss of dorsal-ventral patterning of the cone-opsin gradient. Loss of LDHA in the retina resulted in increased glucose availability, promoted Oxidative Phosphorylation, and upregulated the expression of glutamine synthetase (GS), a neuron survival factor. However, lacking LDHA in Müller cells does not affect visual function in mice. Glucose shortage is associated with retinal diseases, such as age-related macular degeneration (AMD), and regulating the levels of LDHA may have therapeutic relevance. These data demonstrate the unique and unexplored roles of LDHA in the maintenance of a healthy retina.

Keywords
Warburg effect; aerobic glycolysis; lactate dehydrogenases; photoreceptors; retina.
Products