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M. J. Murphy Edwards, S. G. Crewther, S. N. Kiely, L. Giummarra, M. J. Goodyear, D. P. Crewther; Why Ion Transport Inhibitors and ON/OFF Agents Simultaneously Affect Ocular Growth and Refractive Compensation. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3685.
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We have previously shown that pharmacological agents that affect signal transmission in the retinal ON and OFF pathways or target ion transport systems in the retina influence ocular growth to induced defocus. The current study investigates the association between ocular growth, changes in receptor expression and the amplitude of the ON and OFF waves of the electroretinogram (ERG) in characterizing the direction ocular growth.
Chicks reared for 4 days with induced defocus following injection of a physiological dose of either LAAA, DAAA, Bumetanide, Amiloride, Furosemide or Ouabain were assessed for changes in refraction and ocular dimensions. Tissue was taken for immunohistochemistry. ERG: Under anaesthesia non-lens treated chicks were injected intravitreally with physiological doses of the same drugs and prepared for electrophysiological analysis after 4 days rearing. To measure ERG responses to both ON and OFF light stimulation a square wave 500ms onset 500ms offset ganzfeld was employed.
Biometric analysis showed differential, sign-dependant effects on refractive state and ocular growth following drug injection. Comparison of waveform amplitude and calculation of the ratio of the b/d wave amplitude revealed that agents affected the ON and OFF retinal pathway response in a differential manner. The magnitude of the ON and OFF response (b/d wave ratio) differed systematically between drugs known to alter compensation to +10D or -10D lenses. Early increases in AQP4 expression were associated with development of myopia while later changes in potassium transport channel expression were associated with development of hyperopia.
Results suggest that altered ON/OFF pathway activation associated with changes in the ion channels transporting fluid through Mueller cells and across the subretinal space/retinal pigment epithelium, predict the direction of ocular growth and resultant refraction, thus directly and indirectly supporting the hypothesized role of ionically driven fluid movement dynamics in myopia.
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