Blood-ocular barrier permeability in monkeys.

Area of Science:

• Ophthalmology
• Pharmacokinetics
• Physiology

Background:

• The blood-ocular barrier (BOB) regulates substance passage into the eye.
• Understanding BOB permeability is crucial for drug delivery and disease treatment.
• Active transport mechanisms significantly influence ocular pharmacokinetics.

Purpose of the Study:

• To investigate the inward permeability (Pin) of the blood-retinal barrier (BRB) in non-human primates.
• To compare the transport kinetics of fluorescein (F) and fluorescein monoglucuronide (FG) across ocular barriers.
• To elucidate the role of active transport in the ocular efflux of fluorescein.

Main Methods:

• Kinetic vitreous fluorophotometry (VFP) was employed in five monkeys.
• Intravitreal injections of fluorescein (F) and fluorescein monoglucuronide (FG) were administered.
• Computer simulations were used to calculate inward permeability (Pin) and rates of loss (Ka, Kv).

Main Results:

• The mean inward permeability (Pin) of the BRB was estimated at 4.8 x 10(-6) cm/min.
• Rates of fluorescein loss from the anterior chamber (Ka) and vitreous (Kv) were significantly higher than those of fluorescein monoglucuronide.
• Probenecid administration reduced fluorescein efflux, indicating active transport involvement.

Conclusions:

• Active transport mechanisms play a significant role in fluorescein excretion from the eye.
• Active transport appears more predominant in the blood-retinal barrier compared to the blood-aqueous barrier.
• These findings have implications for understanding ocular drug disposition and developing targeted therapies.