Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice.
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.
F.M. Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lauren L
LL
Daniele
Brian
B
Sauer
Shannon M
SM
Gallagher
Edward N
EN
Pugh
Nancy J
NJ
Philp
D000818:Animals; D051926:Basigin / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004596:Electroretinography; D015870:Gene Expression; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008027:Light; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology / Q000528:radiation effects; D027981:Symporters / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*; D062826:Zonula Occludens-1 Protein; D000099233:Monocarboxylate Transport Protein 1
D051926:Basigin; D002352:Carrier Proteins; D051272:Glucose Transporter Type 1; D019344:Lactic Acid; D008565:Membrane Proteins; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D010750:Phosphoproteins; D027981:Symporters; D062826:Zonula Occludens-1 Protein; D000099233:Monocarboxylate Transport Protein 1; C497886:BSG protein, human; C491392:Slc16a3 protein, mouse; C498648:Slc16a4 protein, mouse; C495678:Slc2a1 protein, mouse; C569042:TJP1 protein, human; C569043:Tjp1 protein, mouse