Effects of fasudil, a Rho-associated protein kinase inhibitor, on optic nerve head blood flow in rabbits.
OBJECTIVE
To investigate the effects of fasudil, a Rho-associated coiled coil-forming protein kinase (ROCK) inhibitor, on normal or impaired optic nerve head (ONH) blood flow in a rabbit model.


METHODS
ONH blood flow was measured by laser speckle flowgraphy. Changes in ONH blood flow were examined during a continuous intravenous infusion of fasudil with and without the application of N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. Effects of topical fasudil on ONH blood flow were investigated in normal eyes or models of ocular circulation impairment induced by the application of endothelin (ET)-1. Visual-evoked potentials (VEPs) and morphologic and histologic changes were also analyzed in the ET-1-injected eyes.


RESULTS
A continuous intravenous infusion of fasudil had no significant effect on normal ONH blood flow, yet it prevented or improved the ONH blood flow impairment induced by the intravenous injection of L-NAME. Repeated intravitreal injections of ET-1 twice a week for 4 weeks decreased the ONH blood flow, prolonged the VEPs' implicit time, enlarged the optic cup, and decreased retinal ganglion cells. Multiple doses of topical fasudil ameliorated the ONH impairments caused by ET-1.


CONCLUSIONS
These results show that systemic or topical fasudil suppresses impairment of ONH blood flow, function, and morphology induced by L-NAME or ET-1. A ROCK inhibitor can be useful for the treatment of impaired ONH blood flow.
Sugiyama
Tetsuya
T
Department of Ophthalmology, Osaka Medical College, Takatsuki, Osaka, Japan. tsugiyama@poh.osaka-med.ac.jp
Shibata
Maho
M
Kajiura
Sumiko
S
Okuno
Takashi
T
Tonari
Masahiro
M
Oku
Hidehiro
H
Ikeda
Tsunehiko
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000287:Administration, Topical; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D019332:Endothelin-1 / Q000494:pharmacology; D005074:Evoked Potentials, Visual / Q000187:drug effects; D007262:Infusions, Intravenous; D007429:Intraocular Pressure / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009898:Optic Disk / Q000098:blood supply*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
D019332:Endothelin-1; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil; D019331:NG-Nitroarginine Methyl Ester