The Muscarinic Antagonist MT3 Distinguishes Between Form Deprivation- and Negative Lens-Induced Myopia in Chicks

Abstract

Purpose: The muscarinic M4 receptor antagonist MT3 (muscarinic toxin 3) is effective at inhibiting the development of myopia in response to form deprivation, and prevents the deprivation-induced choroidal thinning. We asked if it was equally effective in eyes wearing negative lenses. Methods: Chicks wore monocular diffusers or −15 D lenses for 7 days. Intravitreal injections of MT3 (90 nmoles) were given on days 2, 4 and 6 (diffusers: n = 13; lenses: n = 12); saline was used as injection controls (diffusers: n = 11; lenses: n = 13). Ocular dimensions were measured with A-scan ultrasound on days 1 and 7. Refractions were measured using a Hartinger’s refractometer. A third group of “normal” chicks received monocular injections of drug (n = 7) or saline (n = 7), and eyes were measured 3 and 72 h later. Results: MT3 inhibited the myopia in response to form deprivation, but did not affect the compensation to negative lenses (drug versus saline: FD: −3.2 versus −7.4 D; p < 0.001; Lenses: −4.5 versus −4.9 D). The myopia inhibition in deprived eyes was due to inhibition of axial growth (610 µm versus 827 µm; p < 0.005); lens-wearing eyes grew similar to saline controls (747 µm versus 743 µm). There was no effect of the drug on the choroidal thinning in either condition. Unexpectedly, MT3 produced choroidal thinning in normal eyes (drug versus saline: −45 versus 16 µm/3 h; p < 0.05), but had no effect on refractions or ocular growth. Conclusions: MT3 does not inhibit the development of myopia in response to hyperopic defocus. It also causes choroidal thinning, an anomalous effect for a muscarinic receptor antagonist. These results support the existence of different muscarinic mechanisms in the excessive eye growth resulting from the open-loop condition of form deprivation, versus that of hyperopic defocus, a closed-loop condition.