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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Cell Physiology |
| Volume | 295 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 2008 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice
AU - Daniele, Lauren L.
AU - Sauer, Brian
AU - Gallagher, Shannon M.
AU - Pugh Jr, Edward N
AU - Philp, Nancy J.
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
KW - Electroretinogram
KW - Lactate transport
KW - Monocarboxylate transporter 3
KW - pH regulation
KW - Photoreceptor
KW - Retinal pigment epithleium
UR - http://www.scopus.com/inward/record.url?scp=55949087436&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55949087436&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.00124.2008
DO - 10.1152/ajpcell.00124.2008
M3 - Article
C2 - 18524945
AN - SCOPUS:55949087436
VL - 295
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 2
ER -