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Kristen Totonelly, Yekaterina Yusupova, Debora L. Nickla; Muscarinic Agents And Emmetropization In Chicks: Evidence For Separate Pathways For Form-deprivation And Lens-induced Myopia. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6319.
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Acetylcholine is involved in the defocus-induced changes in choroidal thickness: Two muscarinic antagonists, one non-specific and one m1/m4 antagonist, which inhibit ocular growth also cause transient choroidal thickening (Nickla, IMC 2008). Because a highly specific m4 antagonist, MT3, has been shown to block form-deprivation myopia (McBrien et al., ARVO 09), we now ask whether it also blocks lens-induced myopia, and, if so, whether it causes choroidal thickening. Furthermore, because we have found that some muscarinic agonists cause choroidal thinning, we ask whether these agonists have a stimulatory effect on ocular growth.
Ocular dimensions were measured using high frequency A-scan ultrasonography at various intervals. Refractions were measured with a Hartinger’s refractometer. Carbachol: (1) Normal eyes had one intravitreal injection of drug or saline (2mg/ml; n=8,8). (2) Eyes wore -10D lenses for 4d, and were given daily injections prior to a 2 hr period of unrestricted vision (n=18,18). Oxotremorine or Arecaidine: Normal eyes had one injection (n=15, n=10 respectively, 4mg/ml). MT3: (1) Normal eyes received one injection of MT3 (90 nmol; n=7) or saline (n=7). (2) Eyes wore -10D lenses (n=17,17) or diffusers (n=5, 5) for 6d, and were injected on alternate days (n=8,8). All comparisons are between drug and saline-injected eyes.
The m4 antagonist MT3 had no effect on lens-induced myopia (-1.3 vs -2.5 D; p=0.1; axial growth: 585 vs 600 µm), although, as expected, it inhibited deprivation myopia (-3.9 vs -6.9 D; p<0.01) by inhibiting growth (520 vs 689 µm; p=0.01). Surprisingly, in normal eyes, it resulted in rapid (3hrs: -45 vs 16 µm; p<0.05) and long-lasting (72 hrs) choroidal thinning, the opposite of other antagonists, but did not affect ocular growth (250 vs 280 µm/3d). None of the agonists tested had a stimulatory effect on ocular growth; in fact, both carbachol and oxotremorine resulted in ocular growth inhibition in normal eyes (carbachol: 169 vs 307 µm/3d; oxotrem: 541 vs 611 µm/6d; p<0.05). In lens-wearing eyes, carbachol inhibited the choroidal thickening response to brief daily vision (0 vs 78 µm; p<0.001), but had no effect on ocular growth (281 vs 275 µm/3d).
The m4 antagonist MT3 had no effect on lens-induced myopia although it inhibited form-deprivation myopia, implying separate signaling pathways for these two types of myopia. Furthermore, the muscarinic agonists that thinned the choroid did not increase ocular growth, indicating separate pathways for choroidal and axial effects.
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