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

Lauren L Daniele¹, Brian Sauer, Shannon M Gallagher

¹F.M. Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

American Journal of Physiology. Cell Physiology

|June 6, 2008

Summary

Monocarboxylate transporter 3 (Mct3) facilitates lactate transport in the retina. Its absence reduces electroretinogram a-wave amplitude, suggesting Mct3 is vital for outer retinal pH and photoreceptor function.

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Area of Science:

Ophthalmology
Neuroscience
Cell Biology

Background:

Photoreceptor cells require high energy, utilizing glucose metabolism that produces lactate and CO2.
The monocarboxylate transporter 3 (Mct3) is positioned to transport lactate and H+ out of the retina, potentially regulating pH and ion balance.
Mct3 is found in the basolateral membrane of the retinal pigment epithelium and complexes with CD147.

Purpose of the Study:

To investigate the physiological role of Mct3 in retinal function.
To determine the impact of Mct3 deletion on retinal histology, pH, and photoreceptor cell function.

Main Methods:

Generated Mct3-deficient (Mct3(-/-)) mice using targeted deletion (slc16A8).
Assessed retinal histology, CD147 expression, scotopic electroretinograms (ERG), and retinal lactate levels.

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Performed single-cell recordings of rod photocurrents in retinal slices.

Main Results:

Retinal histology was normal in Mct3(-/-) mice.
Basolateral CD147 expression was lost in Mct3(-/-) mice.
Scotopic ERG a-wave amplitude was reduced twofold in Mct3(-/-) mice.
Retinal lactate increased fourfold, indicating decreased outer-retinal pH.
Photoreceptor cells in Mct3(-/-) mice were inherently healthy, with comparable single rod photocurrents.

Conclusions:

Mct3 deletion leads to increased retinal lactate and reduced outer-retinal pH.
The observed reduction in ERG a-wave amplitude is likely due to decreased subretinal space pH.
This pH decrease may reversibly reduce the light-suppressible photoreceptor current, highlighting Mct3's importance in retinal homeostasis.