Sheila Crewther

　　澳大利亚 La Trobe 大学

　　Purpose:-Myopia(short-sightedness)affects over 2 billion people worldwide.In 95%of cases，myopia is due to abnormal ocular volume and axial elongation of the vitreous chamber of the eye，clearly identifying a potential therapeutic target.We have recently shown that both the refractive error and abnormal axial elongation characterizing form deprivation myopia in chicks are associated with dramatic osmoregulatory changes in ion and fluid distribution across the retina/choroid(1，2).We are now interested in whether the abnormal ocular growth induced by optical defocus can be reliably controlled in chicks by drugs which affect osmoregulatory mechanisms，such as barium，which unselectively blocks potassium(K)channels and more specific sodium(Na)and chloride(Cl)cotransporter blocking diuretics such bumetanide(a specific inhibitor of the sodium-potasssium-2chloride NKCC1 cotransporter)，amiloride(specific inhibitor of the sodium/hydrogen(Na/H exchanger and furosemide(a specific KCC2 cotransporter)。

　　Method: Hatchling chickens were raised with monocular optical defocus of±10D or No Lens for 48 or 72 hours from day 5 and then eyes were enucleated and retina/RPE/choroidal tissue prepared for light and electron microscopy and elemental microanalysis.Other chicks were raised with optical defocus or No Lenses and intravitreal injections of barium or diuretic agents bumetanide，amiloride，furosemide or saline，from day 5-9 after which refractive compensation and ocular growth were compared using retinoscopy and ultrasonagraphy

　　Results:Comparison of the ratio of Na，K，and Cl ion concentrations in the lens-wearing eye to fellow eye showed a sign dependent differential pattern across the retina after 48 and 72 hours of optical defocus.Intravitreal barium inhibited refractive compensation to both lens types while bumetanide，furosemide and amiloride only inhibited compensation to-10D lenses。

　　Conclusion:The results demonstrate that optical focus as well as form deprivation induces osmoreulatory changes in the pattern of ion distribution across the retina and in the resultant transretinal fluid movments into vitreous and choroid.The results also indicate that both unspecific K channel blockade and diuretics affect refractive compensation with the more specific NKCC，KCC and Na/H inhibitors showing defocus sign-dependency.Probable sites of action include the apical RPE membrane and the photoreceptor/ON bipolar synapse.The selective inhibition by loop diuretics of refractive compensation to negative lens in chick suggests that these drugs may be effective in the therapeutic management of human myopia.