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Michelle Teves, Qing Shi, William K Stell, Derek Eng; The role of cell-cell coupling in myopia development and light adaptation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3036.
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Myopia is a refractive disorder in which excessive elongation of the eye causes blurring of distance-vision. Dopamine (DA) and nitric oxide (NO), which are released in the retina under light-adaptation, are critical for myopia-prevention and light adaptation. How they work is still poorly understood; but both have been shown to uncouple gap junctions in retinal networks. Therefore, cell-cell coupling in the retina may play a key role in the regulation of ocular growth, e.g., by mediating the effects of light, DA, and NO on spatial contrast sensitivity (CS) in the retina. We tested this hypothesis using a gap junction blocker, meclofenamic acid (MFA), to determine its effect on myopia development and spatial CS.
Form-deprivation myopia (FDM) was induced in 6 day old (P6) White Leghorn cockerels by diffusers over the right eyes (treated, “T”) leaving the left eyes uncovered as controls (C). We injected intravitreally 20 µL of 20 mM MFA in dH2O, or dH2O alone, on P7, P9, and P11. On P12 we measured refractive error, axial length, equatorial length, and eye weight. Treatment effects were expressed as interocular differences (T-C; one-way ANOVA, Tukey post-hoc). The role of cell-cell coupling in light-adaptation in retinal circuitry was assessed by the optokinetic response, using OptoMotry®, before and after injection of 20 mM MFA (as above). Mean intensities were in the low to intermediate photopic range (-0.7 to 2.0 log cd/m2).
In dH2O controls, goggles induced a myopic shift in refractive error (-9 ± 3D, mean ± SD) and excessive axial length (0.9 ± 0.3mm) [T-C]. MFA significantly reduced the induced increases in refractive error (0 ± 2D; p<0.001) and axial length (0.0 ± 0.3mm, p<0.001) [T-C]. Equatorial length and eye weight were not significantly affected by treatment. At the highest luminance, MFA increased CS at medium-high spatial frequencies (SFs) (SF=0.32 cyc/deg, p<0.001; SF=0.5 cyc/deg, p<0.05; SF=0.8 cyc/deg, p<0.01; SF=1.0 cyc/deg, p<0.05, n=8-9, paired t-test), whereas it did not alter CS under dim light (-0.7 log cd/m2).
Intravitreal MFA mimics the actions of increased light intensity, DA, and NO, on form-deprivation myopia and optokinetic contrast sensitivity in chicks. This suggests that uncoupling of gap junctions between retinal neurons may mediate some actions of DA and NO.
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