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T. Da, A.S. Verkman; Aquaporin–4 deletion in mice protects against ischemic retinal injury . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3266.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Aquaporin–4 (AQP4) is water–transporting protein that is strongly expressed in retinal Muller cells. AQP4 is also found in brain astroglia, where it has been shown to be involved in cerebral edema. The purpose of this study was to investigate whether the involvement of AQP4 plays a role in retinal injury caused by ischemia–reperfusion. Methods: Retinal ischemic injury was produced in wildtype and AQP4 deficient mice by elevating intraocular pressure to 120 mmHg for 30, 45 or 60min, using a microneedle inserted into the anterior chamber through the cornea. Retinal morphology was assessed by light microscopy. Functional analysis was done by electroretinography, analyzing the amplitude oscillatory potentials (OPs). Retinal morphology was assessed by light microscopy. Changes in retinal AQP4 expression were quantified by real–time PCR. Results: Histological examination revealed less retinal damage in AQP4 deficient mice. At 12 hours after 60 min ischemia, the inner plexus layer was edematous: its thickness increased by 72.6 ± 5.6% (n=5) in wildtype vs. 52.0 ± 7.4% (n=3) in AQP4–deficient mice, p<0.05. At 4 days after 60 min ischemia, the inner retina layer was degenerated: its thickness decreased by 42.7 ± 4.7% (n=7) in wildtype mice vs. 11.4 ± 4.3% (n=3) in AQP4–deficient mice, p<0.001. Electroretinography revealed relative preservation in AQP4–deficient mice. At 3 days after 30 min ischemia, the amplitudes in OPs were 0.85 mV in wildtype vs. 3.1 mV in AQP4–deficient mice. Quantitative RT–PCR analysis of retina in wildtype mice indicated a 99.1±0.2% (n=4) reduction in AQP4 transcript at 12 hours after a 60 min retinal injury, with return to 72.8±1.24% (n=3) of initial transcript level 4 days after injury, p<0.001. Conclusions: AQP4 deletion in mice protects against ischemia–reperfusion injury. The mechanism of protection remains to be established.
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