Acid-sensing ion channel 3 in retinal function and survival.
OBJECTIVE
Changes in extracellular pH occur in the retina and directly affect retinal activity and phototransduction. The authors analyzed the expression in rodent retina of ASIC3, a sensor of extracellular acidosis, and used ASIC3 knockout mice to explore its role in retinal function and survival.


METHODS
The expression and the role of ASIC3 were examined by immunolocalization and by comparing retinas from wild-type and knockout mice at different ages through electroretinography, retinal histology (light and electron microscopy), expression of glial fibrillary acidic protein (GFAP), analysis of cell apoptosis (TUNEL assay), and patch-clamp recordings in primary cultures of retinal ganglion cells (RGCs).


RESULTS
ASIC3 is present in the rod inner segment of photoreceptors and in horizontal and some amacrine cells. ASIC3 is also detected in RGCs but does not significantly contribute to ASIC currents recorded in cultured RGCs. At 2 to 3 months, knockout mice experience a 19% enhancement of scotopic electroretinogram a-wave amplitude and a concomitant increase of b-wave amplitude without alteration of retinal structure. Older (8-month-old) knockout mice have 69% and 64% reductions in scotopic a- and b-waves, respectively, and reductions in oscillatory potential amplitudes associated with complete disorganization of the retina and degenerating rod inner segments. GFAP and TUNEL staining performed at 8 and 12 months of age revealed an upregulation of GFAP expression in Müller cells and the presence of apoptotic cells in the inner and outer retina.


CONCLUSIONS
Inactivation of ASIC3 enhances visual transduction at 2 to 3 months but induces late-onset rod photoreceptor death, suggesting an important role for ASIC3 in maintaining retinal integrity.
Ettaiche
Mohammed
M
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Université de Nice-Sophia Antipolis, Valbonne, France.
Deval
Emmanuel
E
Pagnotta
Sophie
S
Lazdunski
Michel
M
Lingueglia
Eric
E
D062565:Acid Sensing Ion Channels; D025042:Amacrine Cells / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003623:Dark Adaptation; D004596:Electroretinography; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D055537:Light Signal Transduction; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D012165:Retinal Ganglion Cells / Q000502:physiology*; D051248:Retinal Horizontal Cells / Q000502:physiology*; D055211:Retinal Photoreceptor Cell Inner Segment / Q000502:physiology*; D015222:Sodium Channels / Q000378:metabolism*
C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D005904:Glial Fibrillary Acidic Protein; D015222:Sodium Channels