Mulling over Müller cells: cancer-like metabolism in mammalian retina

T Kittipassorn1,2, JP Wood3,4, T Mammone3,4, RJ Casson3,4 and DJ Peet1

  1. School of Biological Sciences, University of Adelaide, Adelaide, Australia
  2. Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  3. Ophthalmic Research Laboratories, Hanson Institute, Adelaide, Australia
  4. South Australian Institute of Ophthalmology, University of Adelaide, Adelaide, Australia

Mammalian retina, like cancer cells, displays aerobic glycolysis or the Warburg effect whereby the cells tend to convert glucose into lactate via glycolysis regardless of oxygen availability. If mechanisms underlying this phenomenon in cancer and retina are conserved, cancer treatments targeting the Warburg effect might adversely affect the retina. The transcription factor hypoxia-inducible factor-1 (HIF-1) and the glycolytic enzyme pyruvate kinase M2 (PKM2) are implicated in the Warburg effect in cancer; HIF-1 stimulates glycolysis and PKM2 is proposed to promote lactate production. This study aims to investigate whether these two proteins play a similar role in the retina which will contribute to the understanding of retinal metabolism at the molecular level. We recently demonstrated PKM2 expression specifically in photoreceptors in rat and mouse retinas[1], and have also demonstrated that rat primary mixed retinal cultures and cultured retinal Müller cells express both PKM2 and HIF-1 alpha. We present data investigating the relative contributions of PKM2 and HIF-1 to driving the Warburg effect in the retina, using knockdown and chemical inhibition combined with detailed metabolic analysis of isolated cell lines, primary retinal cultures and retinal explants. To facilitate this characterization we also present data on the generation and characterization of a spontaneously immortalized rat Müller cell line.
References: [1] Casson R.J., Wood J.P., Han G., Kittipassorn T., Peet D.J., Chidlow G. (2016) Invest. Ophthalmol. Vis. Sci. 57(1):66-80.