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David P. Crewther, Melanie J. Murphy Edwards, Sarah N. Kiely, Sheila G. Crewther; Interactions Between Retinal On And Off Pathways And Refractive Compensation To Defocus. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6317.
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An interaction between the ON and OFF retinal responses and refractive compensation has been well documented, both in terms of luminance modulation and through pharmacological manipulation of the synaptic mechanisms. Here, we compare the effects of single intravitreal injection of four drugs (known to acutely influence the retinal ON or OFF pathways) on response to rearing with ±10D lens defocus or no lens rearing.
220 male hatchling chicks (Leghorn/ New Hampshire) were raised for 4 days under standard diurnal conditions with 3 lens (±10 D or No Lens) groups. Lensed eyes were iv injected with either 2.5 µmole aminoadipic acid (DAAA or LAAA) or with 0.5 µmole of APB or PDA in 5µl PBS, or with PBS alone. Electroretinography was used to ascertain the effects of the drugs at the end of the rearing period.
LAAA and DAAA showed the expected sign-dependent interference with refractive compensation. However, APB which acutely inhibits the retinal ON response (as does LAAA) did not prevent cmpensation to -10D lenses, resulting in even greater myopia than in -10D PBS controls. ERG recordings showed that at the end of the rearing period, the APB chicks showed continued suppression of the b-wave with a b/d wave ratio of .06 (cf 1.37 in PBS), while in the LAAA chicks, the ON response had recovered and rebounded with a b/d wave ratio of 2.1. b/d ratios in the other two conditions were less than for PBS (DAAA 1.12; PDA 0.64).
Aminoadipic acid interference with refractive compensation in chicks reared under standard diurnal conditions shows a systematic relation to the ERG b/d wave ratios. In contrast, the sustained inhibition of the b-wave under APB conditions and excessive myopia induced under -10D lens conditions suggests that prevention of myopia under negative lens defocus requires a stronger ON than OFF response.
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