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M.J. Murphy, S.G. Crewther, M.J. Goodyear, A. Hazi, D.P. Crewther; Bumetanide Inhibits the Myopic Shift in Refraction and Ocular Growth Induced in Chicks Raised Under Whole Field Low Temporal Frequency Flicker . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1139.
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© ARVO (1962-2015); The Authors (2016-present)
Low temporal frequency luminance modulation (LTFLM) induces a generalized myopic shift in refractive compensation to optical defocus (Crewther et al., In Press), which is not affected by the inhibition of the retinal ON pathways by L–alpha amino adipic acid (LAAA) (McAuley et al., ARVO, 2006). Thus we investigated the effect of LTFLM on the refractive compensation of chicks with intravitreal injection of Bumetanide, an inhibitor of RPE Na+, K+, 2Cl– cotransport system activity known to block the light induced subretinal space volume increase (Marmor, 1998).
Chicks were fitted monocularly with ±10D lenses, or wore no lens, from days 5–10 post–hatching and injected with 5µl of 1 mM bumetanide in PBS carrier solution. Fellow eyes received 5µl of PBS. Chicks were reared under 1Hz 250msec TLM from 1.8–183lux during a 12 hr day/night cycle at 31°C. Biometry including retinoscopy and A–scan ultrasonography was performed and eyes were prepared for histological and immunological analysis.
TLM of 1 Hz inhibited compensation to +10D lenses and resulted in myopic growth to –13D for –10D lens groups. Bumetanide and TLM together induced a mean refraction of ∼4D compensation to +10D lenses, and –9D to –10D lenses, considerably less than TLM alone, but a greater degree of myopia than compensation to bumetanide alone, which showed a mean refraction of –4D. There was no difference in refractive state between TLM, TLM + Bumetamide, and PBS controls for eyes without lenses. Vitreous chamber lengths showed corresponding effects to refractions. A moderately strong effect of TLM and bumetanide was observed in anterior chamber, where depth was more than 0.1 mm shorter for diuretic treated chicks.
Bumetanide, which acts on the RPE Na+, K+, 2Cl– co–transporter, inhibited TLM induced myopia suggesting that RPE fluid channels play an important role in refractive compensation overriding the myopic shift induced by TLM alone.
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