TY - JOUR
T1 - Cyclic-AMP in the aqueous humor
T2 - The effects of adrenergic agents
AU - Neufeld, Arthur H.
AU - Jampol, Lee M.
AU - Sears, Marvin L.
N1 - Funding Information:
Adrenergic agents have a pronounced effect on the formation and the outflow facility of aqueous humor. Catecholamines, administered topically to the eye, decrease the intraocular pressure. This can be demonstrated using laboratory animals but particular interest in this phenomenon ark!8 from its effectiveness as treatment for glaucoma. The clinical value of epinephrine therapy has been recognized since 1923 (Hamburger, 1923), but the biochemical mecha.nismb y which catecholamines lower intraocular pressure is unknown. However, in many tissues, adrenergic agents activate adenyl oyolsse to produce adenosine-3’,5’-cyclic monophosphate (cyclic-AMP) and it is this second messenger which actually mediates the physiological event that the catecholamines i&ate (Robison, Butcher and Sutherland, 1971). We will present evidence suggesting that cyclic-AMP may play a central role in mediating the action of catecholamines on aqueous humor dynamics. Adrener@c agents which decreasei ntraocular pressure, when administered topically to the rabbit t This research wss supported in part by USFHS research grant EY-O0237-11. USPHS center grant EY-OO7S5-01, USPHS training grant EY-O0002-10, NIH contract NIH-NEI-71-2512, and the connecticut Lions Eye Research Foundation, Incorporated.
PY - 1972/11
Y1 - 1972/11
N2 - Adrenergic agents, which reduced intraocular pressure when applied topically to the rabbit eye, increased the cyclic-AMP concentration in the aqueous humor. The order of potency for both reducing intraocular pressure and increasing cyclic-AMP was: epinephrine > norepinephrine > isoproterenol. Intravenous phenoxybenzamine partially blocked the decrease in intraocular pressure and the increase in cyclic-AMP. Intravenous propranolol was ineffective. Topically applied aminophylline, theophylline, and dibutyryl cyclic-AMP were also ineffective. The time course for the epinephrine induced mydriasis was different from the time course for the decrease in intraocular pressure and the increase in cyclic-AMP. The pupil dilated rapidly and then slowly returned to baseline values over the next 4 hr. The intraocular pressure and cyclic-AMP responses peaked at approximately the same time (1·5 hr) and were sustained for at least 5 hr. Substantial tissue levels of cyclic-AMP were found in the cornea, iris-ciliary body and retina-choroid. However, no differences in tissue level could be demonstrated in the control versus epinephrine-treated eye. Thus the site of production of the increased cyclic-AMP in the aqueous humor is not yet resolved. Intracameral injection of high concentrations of cyclic-AMP (estimated final concentration in anterior chamber: 4 × 10-4m) caused a marked decrease in intraocular pressure. Similar injections of 5′AMP into the other eye of the same animal were ineffective. The experiments indicate that cyclic-AMP plays a central role in mediating the action of catecholamines on aqueous humor dynamics. The role of the increase in the aqueous humor and possible sites of production and action of the cyclic-AMP are discussed.
AB - Adrenergic agents, which reduced intraocular pressure when applied topically to the rabbit eye, increased the cyclic-AMP concentration in the aqueous humor. The order of potency for both reducing intraocular pressure and increasing cyclic-AMP was: epinephrine > norepinephrine > isoproterenol. Intravenous phenoxybenzamine partially blocked the decrease in intraocular pressure and the increase in cyclic-AMP. Intravenous propranolol was ineffective. Topically applied aminophylline, theophylline, and dibutyryl cyclic-AMP were also ineffective. The time course for the epinephrine induced mydriasis was different from the time course for the decrease in intraocular pressure and the increase in cyclic-AMP. The pupil dilated rapidly and then slowly returned to baseline values over the next 4 hr. The intraocular pressure and cyclic-AMP responses peaked at approximately the same time (1·5 hr) and were sustained for at least 5 hr. Substantial tissue levels of cyclic-AMP were found in the cornea, iris-ciliary body and retina-choroid. However, no differences in tissue level could be demonstrated in the control versus epinephrine-treated eye. Thus the site of production of the increased cyclic-AMP in the aqueous humor is not yet resolved. Intracameral injection of high concentrations of cyclic-AMP (estimated final concentration in anterior chamber: 4 × 10-4m) caused a marked decrease in intraocular pressure. Similar injections of 5′AMP into the other eye of the same animal were ineffective. The experiments indicate that cyclic-AMP plays a central role in mediating the action of catecholamines on aqueous humor dynamics. The role of the increase in the aqueous humor and possible sites of production and action of the cyclic-AMP are discussed.
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U2 - 10.1016/0014-4835(72)90009-7
DO - 10.1016/0014-4835(72)90009-7
M3 - Article
C2 - 4344979
AN - SCOPUS:0015426561
SN - 0014-4835
VL - 14
SP - 242
EP - 250
JO - Experimental eye research
JF - Experimental eye research
IS - 3
ER -