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.
Daniele
Lauren L
LL
F.M. Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sauer
Brian
B
Gallagher
Shannon M
SM
Pugh
Edward N
EN
Philp
Nancy J
NJ
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