Effects of topical latanoprost on optic nerve head circulation in rabbits, monkeys, and humans.
OBJECTIVE
To evaluate the effect of topically administrated latanoprost on optic nerve head (ONH) circulation in Dutch rabbits, cynomolgus monkeys, and normal humans.


METHODS
The ONH tissue blood velocity (NB(ONH)) was determined using the laser speckle method. Latanoprost (0.005%, 30 microl) was instilled into one eye, and vehicle into the other eye as a control. In rabbits, NB(ONH) was measured for 90 minutes after a single instillation and before and after a 7-day once-daily instillation regimen. In monkeys, NB(ONH) was measured before and after 1, 4, and 7 days of a once-daily instillation regimen. The effect of intravenous indomethacin on the latanoprost-induced NB(ONH) change was also studied in rabbits and monkeys. In humans, the time-course changes in NB(ONH) were measured for 4.5 hours before and after a 7-day once-daily instillation regimen. Intraocular pressure (IOP) and systemic parameters were simultaneously studied in each experiment. All measurements were performed by investigators masked to the experimental condition.


RESULTS
Latanoprost significantly increased NB(ONH) 10% to 19% in treated eyes after a single instillation (P = 0.035) or 7-day instillation regimen (P = 0.035) in rabbits, after a 4-day (P = 0.035) or 7-day (P = 0.035) instillation regimen in monkeys, and after a 7-day (P = 0.013) instillation regimen in humans, whereas there were no significant changes in the vehicle-treated eyes in any of the experiments (P > 0.5). Pretreatment with indomethacin (5 mg/kg) abolished the NB(ONH) increase but not the IOP reduction in latanoprost-treated eyes in rabbits and monkeys. IOP remained unchanged in both eyes in rabbits (P > 0.4), whereas it significantly decreased only in latanoprost-treated eyes in monkeys (P < 0.05) and humans (P < 0.05).


CONCLUSIONS
Topical latanoprost significantly increased ONH blood velocity only in treated eyes in rabbits, monkeys, and humans. This effect was independent of the IOP-reducing effect of latanoprost and probably was associated with local penetration of the drug and the production of endogenous prostaglandins.
Ishii
K
K
Eye Clinic, Omiya Red Cross Hospital, Japan.
Tomidokoro
A
A
Nagahara
M
M
Tamaki
Y
Y
Kanno
M
M
Fukaya
Y
Y
Araie
M
M
D000287:Administration, Topical; D000328:Adult; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D015590:Fluorophotometry; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D008252:Macaca fascicularis; D008297:Male; D009898:Optic Disk / Q000098:blood supply*; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D012039:Regional Blood Flow; D012171:Retinal Vessels / Q000502:physiology
D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D007213:Indomethacin