Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger.
BACKGROUND
Vision is initiated by phototransduction in the outer retina by photoreceptors, whose high metabolic rate generates large CO2 loads. Inner retina cells then process the visual signal and CO2. The anion exchanger 3 gene (AE3/Slc4a3) encodes full-length AE3 (AE3fl) and cardiac AE3 (AE3c) isoforms, catalyzing plasma membrane Cl-/HCO3- exchange in Müller (AE3fl) and horizontal (AE3c) cells. AE3 thus maintains acid-balance by removing photoreceptor-generated CO2 waste.


RESULTS
We report that Slc4a3-/- null mice have inner retina defects (electroretinogram b-wave reduction, optic nerve and retinal vessel anomalies). These pathologic features are common to most human vitreoretinal degenerations. Immunobloting analysis revealed that Na+/HCO3- co-transporter (NBC1), and carbonic anhydrase II and CAXIV, protein expression were elevated in Slc4a3-/- mouse retinas, suggesting compensation for loss of AE3. TUNEL staining showed increased numbers of apoptotic nuclei from 4-6 months of age, in Slc4a3-/- mice, indicating late onset photoreceptor death.


CONCLUSIONS
Identification of Slc4a3 as underlying a previously unrecognized cause of blindness suggests this gene as a new candidate for a subset of hereditary vitreoretinal retinal degeneration.
Alvarez
Bernardo V
BV
Membrane Protein Research Group, Department of Biochemistry, University of Alberta, Edmonton, Canada.
Gilmour
Gregory S
GS
Mema
Silvina C
SC
Martin
Brent T
BT
Shull
Gary E
GE
Casey
Joseph R
JR
Sauvé
Yves
Y
D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D001766:Blindness / Q000209:etiology* / Q000235:genetics; D017931:DNA Primers; D004596:Electroretinography; D005451:Fluorescein Angiography; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008854:Microscopy, Electron