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

Lauren L. Daniele, Brian Sauer, Shannon M. Gallagher, Edward N Pugh Jr, Nancy J. Philp

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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 CO2. 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 (amax) of the scotopic electroretinogram (ERG) was reduced by approximately twofold in Mct3-/- mice relative to wildtype 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 (Jmax) 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume295
Issue number2
DOIs
StatePublished - Aug 2008
Externally publishedYes

Fingerprint

Knockout Mice
Retina
Lactic Acid
Photoreceptor Cells
Retinal Pigment Epithelium
Protons
Histology
Homeostasis
Ions
Light
Glucose
Membranes
Proteins

Keywords

  • Electroretinogram
  • Lactate transport
  • Monocarboxylate transporter 3
  • pH regulation
  • Photoreceptor
  • Retinal pigment epithleium

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice. / Daniele, Lauren L.; Sauer, Brian; Gallagher, Shannon M.; Pugh Jr, Edward N; Philp, Nancy J.

In: American Journal of Physiology - Cell Physiology, Vol. 295, No. 2, 08.2008.

Research output: Contribution to journalArticle

Daniele, Lauren L. ; Sauer, Brian ; Gallagher, Shannon M. ; Pugh Jr, Edward N ; Philp, Nancy J. / Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice. In: American Journal of Physiology - Cell Physiology. 2008 ; Vol. 295, No. 2.
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