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David Crewther, Sarah Kiely, Melanie Murphy, Nina Riddell, Sheila Crewther; Photoreceptor Outer Retinal Function as the Primary Controller of Ocular Growth. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4041. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Although balanced modulation of retinal responses to light onset and offset have been implicated in refractive compensation (RC) to defocus, the locus of ocular growth control has not been established. Thus, we compared the effects on RC, of pharmacological inhibition of the ON bipolar MGluR6 receptors by 2-amino-4-phosophonobutyrate (APB), and OFF bipolar ionotrophic receptors by cis-2,3-piperidicarboxylic acid (PDA), in combination with either normal diurnal light (ND) or low frequency flicker (LFF)
Hatchling chicks were reared from days 5 -9 in one of three lens conditions (+ or -10D or No Lens) after receiving a single intravitreal injection of APB, PDA or Phosphate Buffered Saline (PBS) in one of three lens conditions under either ND or 1 Hz LFF light. Biometric responses were measured on day 9. Electroretinograms (ERGs) were measured at 0 and 96 hours to determine acute and long term effects of drugs in No Lens chicks (n=22).
Neither APB nor PDA significantly perturbed RC in ND compared with PBS. Under LFF, APB did not affect expected RC cf PBS. However, PDA_LFF chicks were relatively more hyperopic under both -10D and +10D lens conditions than the PBS chicks and affected both -10D and +10D lens ultrasound biometrics. ERGs demonstrated that APB suppressed b-wave amplitude and greatly reduced c-wave amplitude over the rearing period. PDA initially induced acute suppression of photoreceptor a- and d-waves and enhanced the b-wave, and increased the amplitude of the c-wave, with a-, c- and d-waves showing some recovery at 96 hours.
Results in ND light conditions indicate that neither mGLuR6 nor inner retinal ON and OFF pathways play a dominant role in RC to optical defocus. By comparison, the dramatic effect of LFF modulation of the photoreceptors and the surrounding ionic environment on RC to positive lens defocus was unaffected by APB. However LFF + PDA affected RC of both ± lens groups, and after consideration of the ERG results, this suggests a primarily outer retinal driver of abnormal ocular growth mechanisms.
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