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Sally A. McFadden, Rhianna Gambrill, Amelia J. Leotta, Hannah E. Bowrey, Guang Zeng; Inhibition of GABAc Slows Ocular Growth and Myopia in the Mammalian Eye. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6306.
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© ARVO (1962-2015); The Authors (2016-present)
Myopia is a leading cause of vision impairment and blindness throughout the world and involves excessive ocular growth induced by aberrant visual signals located in the retina. One candidate pathway may involve the GABAc receptor, which is located in both plexiform layers of the retina and predominantly on the axon terminals of the bipolar cells. We studied the effects of the selective GABAc antagonist (1,2,5,6-Tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) in a mammalian model of myopia in which myopia was induced with negative lenses or form deprivation (FD).
In Experiment 1, 9 guinea pigs received seven daily intravitreal injections through the pars plana of either 10 µg/ml of TPMPA or a vehicle control in one eye, while simultaneously wearing a -6D lens on the treated eye from 5-12 days of age to induce myopia. In Experiment 2, 24 guinea pigs received three daily injections of 100 µg/ml of TMPMA or vehicle in one eye while simultaneously wearing a diffuser on the treated eye from 5-8 days of age to induce myopia or were given vehicle injections without any FD. Refractive error and the axial depth of each ocular component (using high frequency ultrasound) were assessed at the end of the lens-wearing period.
In Experiment 1, both drug- and vehicle-injected animals developed the same amount of relative myopia (drug: -5.9D; vehicle: -5.3D, p<0.001) but TPMPA caused the vitreous chamber to became smaller (difference between the eyes, drug: -207 µm; p < 0.05; vehicle: -103 µm, not significant). In Experiment 2, vehicle only injections without diffuser-wear had no effect on refractive error, but the ocular length was smaller in every injected eye (mean difference of -108 µm; p < 0.05). FD eyes treated with TPMPA were significantly less myopic than vehicle-injected eyes (difference between the eyes; TPMPA: -1.3D, not significant; Vehicle: -3.6, p < 0.05), and also showed greater inhibition in ocular length (TPMPA: -181 µm, p < 0.001; Vehicle, -84 µm, p < 0.05) due to a significantly smaller vitreous chamber (difference between the eyes; TPMPA: -131 µm; Vehicle: -66 µm; p < 0.05).
The GABAc antagonist, TPMPA, can inhibit ocular growth and myopia in the mammalian eye implicating retinal pathways which involve the GABAc receptor in the control of myopia.
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