ASOPRSFall Scientific SymposiumSyllabus
193
T38
Estrogen IncreasesAquaporin-1MediatedMembranePermeability:
ANewPathophysiologicMechanism for Idiopathic Intracranial Hypertension
MarcYonkersMD/PhD, SarahFarukhiMD, JimHall PhD, Robert CrowMD, Jeremiah TaoMD. Department of Ophthalmology,
University of California IrvineGavinHerbert Eye Institute, Irvine, CA, UnitedStates
Introduction:
We hypothesize that estrogen regulates aquaporin-1 (AQP1) function to increasemembrane permeability as a
proposed pathophysiologicmechanism for idiopathic intracranial hypertension (IIH).
Methods:
IIH primarily affects obese females of child bearing age, a population exposed to high concentrations of endogenous
estrogen.To assess the contribution of estrogen to increased cerebrospinal fluid (CSF) pressure,we examined the effect of estrogen
onAQP1, awater channel expressed in the choroid plexus
1
.To study the interaction of estrogen andAQP1,we injectedAQP1
cRNA into xenopus oocytes and assessed aquaporin protein function viamembrane permeability. Oocyteswere exposed to control
solution or estrogen (10 µM) for an incubation period of two days, and then placed in a hypotonic solution to induce rapid swelling.
The increase in cross sectional area of the oocytewasmeasured over a period of twominutes to determinemembrane permeability.
Permeabilitywas compared between oocytes injectedwithAQP1 cRNA versus vehicle solution and both groupswere exposed to
either estrogen or control solution during the incubation period.
Results:
Oocytes injectedwithAQP1 and incubated in 10 µM estradiol showed a significantly higher permeability rate (95.42±
8.03 µm/s; n=5) compared to oocytes injectedwithAQP1 and incubated in control solution (68.89± 12.70 µm/s; n=4) (p<0.05).
Oocytes injectedwith vehicle alone showed no difference in permeability ratewhen incubated in control solution (7.35± 2.10 µm/s;
n=3) versus incubation in 10 µM estradiol (8.12±2.03 µm/s; n=3).
Conclusions:
Estrogen increasesAQP1mediatedmembrane permeability in xenopus oocytes. Given thewidespread expression
of AQP1 in the choroid plexus, an estrogen induced increase inAQP1 functionmay contribute to increasedCSF pressure and
clinical IIH.These data identify the estrogen-AQP1 interaction as a potential molecular target for improved drug development in IIH.
References:
1. Owler BK, Pitham,T, andDongweiW.Aquaporins: relevance of cerebrospinal fluid physiology and therapeutic
potential in hydrocephalus. Cerebrospinal Fluid Res 20107: 1-12
DetailedProgram
—Thursday,October 16, 2014
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