Effects of nicotinic antagonists on ocular growth and experimental myopia

PURPOSE. To learn whether nicotinic cholinergic receptors modulate postnata l eye growth and influence the course of form-deprivation myopia. METHODS. One-week-old White Leghorn chicks wore a unilateral goggle to indu ce form-deprivation myopia. Other chicks were never goggled. Nicotinic anta gonist drugs were administered by intravitreal injection, usually daily or every other day to the goggled eye or to one eye of never-goggled chicks. A fter 1 week, the eyes were studied by refractometry, A-scan ultrasonography , and caliper measurements. RESULTS. The relatively non-subtype-specific channel-blocking nicotinic ant agonists chlorisondamine and mecamylamine each inhibited the development of form-deprivation myopia but with complex multiphasic dose responses. Chlor isondamine was the most effective. Mecamylamine, at the lowest tested doses , tended to stimulate the growth response and myopic refractive shift of go ggle wearing. Methyllycaconitine competitively inhibits nicotinic receptors containing the alpha7 and alpha8 subunits,which are highly expressed in ch ick retina. It showed a less dramatic but still significant inhibitory effe ct on myopia. The effects of dihydro-beta -erythroidine, a competitive anta gonist relatively selective for nicotinic receptors with alpha3 or alpha4 s ubunits and particularly for alpha3 beta2-containing receptors, were the we akest and inhibited primarily axial elongation. Chlorisondamine but not mec amylamine also affected nongoggled eyes, inhibiting growth and shifting ref raction toward hyperopia, but chlorisondamine also induced degenerative cha nges to the retinal pigment epithelium (RPE). CONCLUSIONS. Nicotinic receptors are involved in eye growth control. Nicoti nic antagonists affect the development of form-deprivation myopia and perha ps the growth of nongoggled eyes. The differences in drug activity and mult iphasic dose-response curves may reflect the complexity of nicotinic recept or subtypes associated with the eye and/or pharmacokinetic differences betw een the individual drugs. Although another tissue(s) cannot be completely e xcluded by these data, the site of action of these agents may be neural ret ina or RPE.