Reduced expression of aquaporin-9 in rat optic nerve head and retina following elevated intraocular pressure.
OBJECTIVE
To investigate the effect of chronically elevated intraocular pressure (IOP) on the expression of water channel aquaporins (AQPs) 1, 4, and 9 in the optic nerve and retina in rats.


METHODS
Three episcleral veins were cauterized to elevate IOP in the left eyes of Sprague-Dawley rats. IOPs were monitored with a rebound tonometer. At 2 and 4 weeks after surgery, eyeballs with the attached optic nerve were enucleated for cryosectioning with immunohistochemistry, or dissected retinas and desheathed optic nerves were subjected to gene expression analyses.


RESULTS
IOP was significantly increased after surgery up to 4 weeks (P=0.0008). In the control optic nerve, the unmyelinated portion showed only AQP9 immunoreactivity, whereas the myelinated portion expressed both AQP4 and AQP9 immunoreactivities colabeled for glial fibrillary acidic protein but not for neurofilament. In the control retina, AQP1 was expressed in the outer nuclear layer and photoreceptors, AQP4 was expressed in Müller cell endfeet, and AQP9 was expressed primarily in NeuN-positive cells in the ganglion cell layer (GCL). Elevated IOPs substantially reduced AQP9 expression in the optic nerve head (ONH) and the GCL and decreased the retinal gene expression, but not immunoreactivity, of AQP1.


CONCLUSIONS
AQP9 was the only water channel expressed in the unmyelinated portion of the ONH and in the GCL whose expression was reduced after IOP elevation. Given that AQP9 presumably acts as a channel for metabolites to pass from astrocytes to neurons, the reduced expression of AQP9 at these specific sites may be implicated in the pathogenesis of glaucomatous optic neuropathy.
Naka
Maiko
M
Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Kanamori
Akiyasu
A
Negi
Akira
A
Nakamura
Makoto
M
D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism; D020346:Aquaporins / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D005901:Glaucoma / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000502:physiology*; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D009898:Optic Disk / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C496022:Aqp1 protein, rat; C496032:Aqp4 protein, rat; C491637:Aqp9 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D012333:RNA, Messenger; D051398:Aquaporin 1