July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Lactate transporters are essential for maintain function in rod but not cone photoreceptor cells.
Author Affiliations & Notes
  • John Yeong Se Han
    Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Junzo Kinoshita
    Cole Eye Institue, Cleveland Clinic, Cleveland, Ohio, United States
  • Jianhai Du
    Department of Ophthalmology, Department of Biochemistry, West Virginia University Eye Institute, Morgantown, West Virginia, United States
  • Sara Bisetto
    Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Brent A. Bell
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Romana Nowak
    University of Illinois at Urbana-Champaign, Urbana-Champaign, Illinois, United States
  • Neal S Peachey
    Cole Eye Institue, Cleveland Clinic, Cleveland, Ohio, United States
    Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, United States
  • Nancy J Philp
    Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   John Han, None; Junzo Kinoshita, None; Jianhai Du, None; Sara Bisetto, None; Brent Bell, None; Romana Nowak, None; Neal Peachey, None; Nancy Philp, None
  • Footnotes
    Support  NIH R01 EY012042, T32AA007463
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1667. doi:
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      John Yeong Se Han, Junzo Kinoshita, Jianhai Du, Sara Bisetto, Brent A. Bell, Romana Nowak, Neal S Peachey, Nancy J Philp; Lactate transporters are essential for maintain function in rod but not cone photoreceptor cells.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1667.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Glucose transported into the outer retina is metabolized primarily through aerobic glycolysis generating large amounts of lactate. Transport of lactate within and out the retina is facilitated by proton-coupled monocarboxylate transporters (MCTs), that require an accessory protein Bsg for proper trafficking to the plasma membrane. Mice with a global knockout of Bsg have severely reduced photopic and scotopic ERGs and a loss of MCTs in the RPE and neural retina. Since there is some controversy in the literature about whether photoreceptor cells produce or oxidize lactate, we generated transgenic mouse lines with Bsg-/- knocked out of rod (RPC) or cone photoreceptors (CPC) to address this issue.

Methods : Mice carrying floxed alleles for Bsg (BsgFlox/Flox) were crossed with Cre transgenic lines that target cone (ConeΔBsg) or rods (RodΔBsg). Retinal structure and function were assessed over time in BsgFlox/Flox Cre transgenic mice and control littermates by spectral-domain optical coherence tomography (SD-OCT) and electroretinograms (ERGs). Metabolomics and biochemical techniques were used to determine the metabolic changes of the retina in RodΔBsg mice. Histological and immunofluorescence (IF) confocal microcopy were used to assess changes in retinal structure and protein expression.

Results : ERGs were recorded from RodΔBsg, ConeΔBsg, and age match control mice over a period of 1 month to 8 months of age. RodΔBsg mice developed a progressive loss of rod function beginning at 2 months of age which was correlated with thinning of the ONL observed by SD-OCT. Cone function was largely spared in RodΔBsg mice. In comparison, ConeΔBsg ERGs were comparable to control mice at 2 months of age and at later ages, we noted a modest decrease in cone function that was not correlated with cone cell death. GC/MS analysis of metabolites from freshly isolated control and RodΔBsg retinas showed an increase in overall levels of lactate, suggesting export of lactate was inhibited in RPC. Retinas isolated from control and RodΔBsg mice were incubated in [U-13C] lactate to determine if there were changes in lactate uptake. We found that there was a decrease in in [U-13C] lactate levels in the RodΔBsg retinas compared to controls as well as a reduction in labeled TCA intermediates.

Conclusions : RPC both produce and utilize lactate while CPC do not seem to rely on lactate transporters to maintain metabolic homeostasis.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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