Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice

Am J Physiol Cell Physiol. 2008 Aug;295(2):C451-7. doi: 10.1152/ajpcell.00124.2008. Epub 2008 Jun 4.


To meet the high-energy demands of photoreceptor cells, the outer retina metabolizes glucose through glycolytic and oxidative pathways, resulting in large-scale production of lactate and CO(2). Mct3, a proton-coupled monocarboxylate transporter, is critically positioned to facilitate transport of lactate and H(+) out of the retina and could therefore play a role in pH and ion homeostasis of the outer retina. Mct3 is preferentially expressed in the basolateral membrane of the retinal pigment epithelium and forms a heteromeric complex with the accessory protein CD147. To examine the physiological role of Mct3 in the retina, we generated mice with a targeted deletion in Mct3 (slc16A8). The overall retinal histology of 4- to 36-wk-old Mct3(-/-) mice appeared normal. In the absence of Mct3, expression of CD147 was lost from the basolateral but not apical RPE. The saturated a-wave amplitude (a(max)) of the scotopic electroretinogram (ERG) was reduced by approximately twofold in Mct3(-/-) mice relative to wild-type mice. A fourfold increase in lactate in the retina suggested a decrease in outer-retinal pH. In single-cell recordings from superfused retinal slices, saturating amplitudes of single rod photocurrents (J(max)) were comparable indicating that Mct3(-/-) mouse photoreceptor cells were inherently healthy. Based on these data, we hypothesize that disruption of Mct3 leads to a potentially reversible decrease in subretinal space pH, thereby reducing the magnitude of the light suppressible photoreceptor current.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basigin / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Electroretinography
  • Gene Expression
  • Glucose Transporter Type 1 / metabolism
  • Lactic Acid / metabolism
  • Light
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron
  • Monocarboxylic Acid Transporters / metabolism
  • Muscle Proteins / metabolism
  • Phosphoproteins / metabolism
  • Photoreceptor Cells, Vertebrate / cytology
  • Photoreceptor Cells, Vertebrate / physiology
  • Photoreceptor Cells, Vertebrate / radiation effects
  • Pigment Epithelium of Eye / cytology
  • Pigment Epithelium of Eye / metabolism
  • Pigment Epithelium of Eye / physiology*
  • Retina / cytology
  • Retina / metabolism
  • Retina / ultrastructure
  • Retinal Rod Photoreceptor Cells / physiology
  • Retinal Rod Photoreceptor Cells / radiation effects
  • Symporters / metabolism
  • Tight Junctions / metabolism
  • Vision, Ocular / physiology*
  • Zonula Occludens-1 Protein


  • BSG protein, human
  • Carrier Proteins
  • Glucose Transporter Type 1
  • Membrane Proteins
  • Monocarboxylic Acid Transporters
  • Muscle Proteins
  • Phosphoproteins
  • Slc16a3 protein, mouse
  • Slc16a4 protein, mouse
  • Slc2a1 protein, mouse
  • Symporters
  • TJP1 protein, human
  • Tjp1 protein, mouse
  • Zonula Occludens-1 Protein
  • monocarboxylate transport protein 1
  • Basigin
  • Lactic Acid