Effects of intravitreal cholera toxin on adenosine 3',5'-monophosphate, intraocular pressure, and outflow facility in rabbits.

Catecholamines, prostaglandins, and various hormones may influence aqueous humor dynamics via the second messenger, adenosine 3',5'-monophosphate (cyclic AMP). To test this hypothesis in rabbit ocular tissues, we have investigated the effects of cholera toxin (CTX), a specific, irreversible activator of adenylate cyclase. CTX (5 x 10(-4) to 5 x 10(2) microgram/ml) in both the presence and absence of isobutylmethylxanthine (IBMX) increased cyclic AMP production in the isolated iris-ciliary body. The effects of CTX were dependent on its concentration, duration of exposure, and presence of IBMX. Furthermore, iris-ciliary bodies and scleral-trabecular rings exercised after intravitreal injection of 10 microgram of CTX and incubated in vitro produced significantly more cyclic AMP than contralateral control tissues. Thus significant binding of CTX to both iris-ciliary body and scleral-trabecular ring occurred within 5 hr after intravitreal injection. Intraocular pressure (IOP) and outflow facility were measured by intraocular cannulation. Five hours after intravitreal injection of CTX, the IOP was lower than in control eyes. At this time, the outflow facility was threefold greater in the CTX-treated eyes than in control eyes. On the basis of these results, we conclude that (1) CTX stimulates cyclic AMP production in iris-ciliary body and scleral-trabecular ring of rabbits, (2) IOP decreases and outflow facility increases after intravitreal injection of CTX, and (3) the hypotensive effect of CTX is apparently mediated, at least partially, by outflow mechanisms.