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Updated: Jul 18, 2026

Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs
Published on: July 23, 2016
Aqueous humor dynamics associated with the phorbol ester-induced decrease in intraocular pressure in the rabbit
Takayuki Oka1, Toru Taniguchi2, Yoshiaki Kitazawa2
1Research Laboratories, Senju Pharmaceutical Company, Ltd., Kobe, Japan. takayuki-oka@senju.co.jp.
Insights
Protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) injection in rabbits reduced intraocular pressure (IOP) by increasing uveoscleral outflow. This IOP-lowering effect may involve PKC activation.
Area of Science:
- Ophthalmology
- Pharmacology
- Physiology
Background:
- Intraocular pressure (IOP) is a critical factor in ocular health.
- Protein kinase C (PKC) plays a role in regulating various cellular functions, including those in the eye.
Purpose of the Study:
- To investigate the impact of phorbol 12-myristate 13-acetate (PMA), a PKC activator, on intraocular pressure (IOP) and aqueous humor dynamics.
- To explore the potential of PMA as a therapeutic agent for managing IOP.
Main Methods:
- Unanesthetized rabbits received intracameral injections of PMA (3-50 pmol).
- Intraocular pressure (IOP) was monitored for 24 hours post-injection.
- Aqueous humor dynamics, including aqueous flow and outflow facility, were assessed.
Main Results:
- PMA induced a biphasic effect on IOP: a transient increase followed by a sustained decrease.
- The IOP-lowering effect was dose-dependent and persisted even after indomethacin pretreatment.
- PMA significantly increased uveoscleral outflow but did not affect aqueous flow or total outflow facility.
Conclusions:
- Intracameral PMA administration effectively reduces IOP in rabbits.
- The primary mechanism for IOP reduction is the enhancement of uveoscleral outflow.
- PKC activation is likely involved in mediating the IOP-lowering effects of PMA.
Purpose:
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.
Conclusion:
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.
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