Effects of nicotinic antagonists on ocular growth and experimental myopia.
OBJECTIVE
To learn whether nicotinic cholinergic receptors modulate postnatal eye growth and influence the course of form-deprivation myopia.


METHODS
One-week-old White Leghorn chicks wore a unilateral goggle to induce form-deprivation myopia. Other chicks were never goggled. Nicotinic antagonist drugs were administered by intravitreal injection, usually daily or every other day to the goggled eye or to one eye of never-goggled chicks. After 1 week, the eyes were studied by refractometry, A-scan ultrasonography, and caliper measurements.


RESULTS
The relatively non-subtype-specific channel-blocking nicotinic antagonists chlorisondamine and mecamylamine each inhibited the development of form-deprivation myopia but with complex multiphasic dose responses. Chlorisondamine was the most effective. Mecamylamine, at the lowest tested doses, tended to stimulate the growth response and myopic refractive shift of goggle wearing. Methyllycaconitine competitively inhibits nicotinic receptors containing the alpha7 and alpha8 subunits, which are highly expressed in chick retina. It showed a less dramatic but still significant inhibitory effect on myopia. The effects of dihydro-beta-erythroidine, a competitive antagonist relatively selective for nicotinic receptors with alpha3 or alpha4 subunits and particularly for alpha3beta2-containing receptors, were the weakest and inhibited primarily axial elongation. Chlorisondamine but not mecamylamine also affected nongoggled eyes, inhibiting growth and shifting refraction toward hyperopia, but chlorisondamine also induced degenerative changes to the retinal pigment epithelium (RPE).


CONCLUSIONS
Nicotinic receptors are involved in eye growth control. Nicotinic antagonists affect the development of form-deprivation myopia and perhaps the growth of nongoggled eyes. The differences in drug activity and multiphasic dose-response curves may reflect the complexity of nicotinic receptor subtypes associated with the eye and/or pharmacokinetic differences between the individual drugs. Although another tissue(s) cannot be completely excluded by these data, the site of action of these agents may be neural retina or RPE.
Department of Ophthalmology, Scheie Eye Institute. stone2@mail.med.upenn.edu
R A
RA
Stone
R
R
Sugimoto
A S
AS
Gill
J
J
Liu
C
C
Capehart
J M
JM
Lindstrom
D000818:Animals; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000000981:diagnostic imaging / Q000254:growth & development* / Q000378:metabolism; D007267:Injections; D023421:Models, Animal; D009216:Myopia / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D012160:Retina / Q000187:drug effects / Q000473:pathology; D012683:Sensory Deprivation; D014463:Ultrasonography; D014822:Vitreous Body
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic