Endothelin-1 impairs retrograde axonal transport and leads to axonal injury in rat optic nerve.
The purpose of this study was to examine the effects of endothelin-1 (ET-1) on retrograde axonal transport in the rat optic nerve. Vehicle or ET-1 (0.2, 1, or 5 pmol/eye) were injected into the vitreous body in Sprague-Dawley rats. Retinal vessels were observed, using a fundus camera, before, and at 10 min, 3 days and 7 days after a single intravitreous injection. Two days after the injection, a neuronal tracer, fluoro gold, was administered via the superior colliculi to retrogradely label active retinal ganglion cells (RGCs). Five days after the tracer administration, retrogradely labeled RGCs were evaluated in the flat-mounted retina, and cross sections from each optic nerve were graded for injury by four independent, masked observers. ET-1 at 5 pmol/eye caused a significant constriction of retinal vessels (versus the vehicle-treated group) at 10 min after the injection. Intravitreous injection of ET-1 caused a dose-related decrease in the number of retrogradely labeled RGCs. Injection of 5 pmol/eye ET-1 led to a statistically significant decrease in the number of retrogradely labeled RGCs (versus the vehicle-treated group). ET-1 at 1 and 5 pmol/eye caused histological optic nerve damage (evaluated using a graded scale). The histological optic nerve damage correlated with the number of retrogradely labeled RGCs. In conclusion, a single intravitreous injection of ET-1 impaired retrograde axonal transport in the rat optic nerve and this impairment correlated with the histological optic nerve damage.
Taniguchi
Takazumi
T
Glaucoma Group, Research and Development Center, Santen Pharmaceutical Co. Ltd, Nara, Japan.
Shimazawa
Masamitsu
M
Sasaoka
Masaaki
M
Shimazaki
Atsushi
A
Hara
Hideaki
H
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects* / Q000502:physiology; D001369:Axons / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000009:adverse effects* / Q000378:metabolism; D005902:Glaucoma, Open-Angle / Q000150:complications / Q000503:physiopathology*; D008297:Male; D009898:Optic Disk / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D018917:Optic Neuropathy, Ischemic / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012161:Retinal Artery / Q000187:drug effects / Q000503:physiopathology; D012162:Retinal Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D013266:Stilbamidines; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014855:Wallerian Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D019332:Endothelin-1; D013266:Stilbamidines