Aqueous humor dynamics associated with the phorbol ester-induced decrease in intraocular pressure in the rabbit.
OBJECTIVE
To determine the effects of injection of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) into the anterior chamber of the eye on intraocular pressure (IOP) and aqueous humor dynamics.


METHODS
IOP was measured for 24 h after intracameral injection of PMA (3 to 50 pmol) in unanesthetized rabbits. Aqueous humor dynamics (aqueous flow, total outflow facility, and uveoscleral outflow) were determined approximately 6 h after injection of 50 pmol of PMA in animals pretreated with indomethacin.


RESULTS
Intracameral injection of 50 pmol of PMA induced a biphasic effect on IOP, consisting of a transient increase apparent at 0.5 and 1 h and a sustained decrease apparent after 2 h. This effect of PMA was dose dependent. Whereas pretreatment with indomethacin attenuated the PMA-induced increase in IOP, the sustained decrease in IOP remained apparent in the pretreated rabbits. Intracameral injection of 4alpha-PMA, an inactive PMA analog, had no effect on IOP. PMA also significantly increased uveoscleral outflow, but it had no effect on aqueous flow or total outflow facility.


CONCLUSIONS
Intracameral injection of PMA reduced IOP in the rabbits by increasing the rate of uveoscleral outflow. This IOP-lowering effect of PMA may be mediated by activation of PKC.
Oka
Takayuki
T
Research Laboratories, Senju Pharmaceutical Company, Ltd., Kobe, Japan. takayuki-oka@senju.co.jp.
Taniguchi
Toru
T
Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan.
Kitazawa
Yoshiaki
Y
Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan.
Sagara
Takeshi
T
Department of Ophthalmology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.
Nishida
Teruo
T
Department of Ophthalmology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.
D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001082:Aqueous Humor / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D007213:Indomethacin / Q000008:administration & dosage; D007267:Injections; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014065:Tonometry, Ocular
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin