Mildly abnormal retinal function in transgenic mice without Müller cell aquaporin-4 water channels.
OBJECTIVE
Immunocytochemistry showed strong aquaporin (AQP)-4 water channel expression in Müller cells in mouse retina and fibrous astrocytes in optic nerve. This study was designed to test the hypothesis that AQP4 is required for vision by comparing electroretinograms and retinal morphology in wild-type mice and transgenic knockout mice with no AQP4.


METHODS
Electroretinograms were recorded over a 10(5)-fold range of flash intensities in dark-adapted mice and analyzed for a- and b-wave amplitude and latency, a-wave normalized slope, and oscillatory potential amplitude and latency. AQP4 protein was localized in mouse retina by immunocytochemistry, and retinal morphology was studied by light and electron microscopy.


RESULTS
Significantly reduced electroretinogram b-wave potentials were recorded in 10-month-old null mice with smaller changes in 1-month-old mice. Immunocytochemistry showed strong AQP4 protein expression in retina of wild-type mice. Morphologic analysis of retina by light and electron microscopy showed no differences in retinal ultrastructure.


CONCLUSIONS
Retinal function is mildly impaired in AQP4-null mice, suggesting a role for AQP4 in Müller cell fluid balance. These results support the paradigm that AQP4 expression in supportive cells in the nervous system facilitates neural signal transduction in nearby electrically excitable cells.
Li
Jiang
J
Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA.
Patil
Rajkumar V
RV
Verkman
A S
AS
D000818:Animals; D051401:Aquaporin 4; D020346:Aquaporins / Q000172:deficiency / Q000502:physiology*; D004596:Electroretinography; D019084:Fluorescent Antibody Technique, Indirect; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism* / Q000648:ultrastructure; D012160:Retina / Q000502:physiology*; D012164:Retinal Diseases / Q000209:etiology* / Q000503:physiopathology; D015398:Signal Transduction; D014882:Water-Electrolyte Balance / Q000502:physiology*
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D020346:Aquaporins