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Pyruvate kinase M2 isoform deletion in cone photoreceptors results in age-related cone degeneration

Ammaji Rajala1,2, Yuhong Wang1,2, Krutik Soni1,2

  • 1Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Cell Death & Disease
|July 5, 2018
PubMed

Insights

Pyruvate kinase M2 (PKM2) is vital for cone photoreceptor health, maintaining their structure and function. Loss of PKM2 leads to cone degeneration, highlighting its essential role in cone metabolism and survival.

Area of Science:

  • Cellular metabolism
  • Retinal biology
  • Molecular ophthalmology

Background:

  • Pyruvate kinase M2 (PKM2), a tumor-associated metabolic enzyme, promotes anabolism by influencing glycolysis and the pentose phosphate pathway (PPP).
  • PKM2 is expressed in both rod and cone photoreceptors, with established importance for rod structure and function.
  • The specific role of PKM2 in cone photoreceptors remains largely unknown.

Purpose of the Study:

  • To investigate the functional role of PKM2 in cone photoreceptor structure, function, and survival.
  • To elucidate the metabolic consequences of PKM2 loss in cones.

Main Methods:

  • Conditional deletion of PKM2 specifically in cone photoreceptors (cone-cre PKM2-KO).
  • Assessment of cone function and structure through age-dependent studies.
  • Gene expression analysis to identify affected metabolic pathways.
  • Measurement of cone outer segment length.

Main Results:

  • Loss of PKM2 in cones led to upregulation of PKM1 and significant cone dysfunction and degeneration in an age-dependent manner.
  • Gene expression studies revealed decreased expression of genes involved in glycolysis, PPP shunt, and fatty acid biosynthesis in PKM2-deficient cones.
  • Cones lacking PKM2 exhibited significantly shorter outer segments compared to control cones.

Conclusions:

  • PKM2 is essential for maintaining cone photoreceptor anabolism, supporting normal function and structure.
  • PKM2 plays a critical role in cone viability and survival.
  • Targeting PKM2 may offer therapeutic potential for cone-related retinal diseases.

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