Ocular hypotensive effects of topically administered agmatine in a chronic ocular hypertensive rat model.
Agmatine, a primary polyamine and potential neuromodulator, exhibits a high affinity to the alpha2-adrenergic receptor as well as imidazoline receptors. As alpha2-adrenergic receptor agonists display positive ocular hypotensive effects, we assessed whether agmatine effectively lowers intraocular pressure (IOP) using a chronic ocular hypertensive rat model. We raised IOP in unilateral eyes of Sprague-Dawley rats by cauterizing three episcleral veins per eye. Four weeks later, we topically administered 10(-3) M agmatine solution 4 times a day for 6 consecutive weeks. After confirming the recovery of IOP to pretreatment level at 13 weeks after cauterization, the retinal ganglion cells (RGCs) were retrogradely labeled and counted. Eyes subjected to episcleral vein cauterization (EVC) demonstrated significant increases in IOP (48.39% increase over baseline IOP), and the elevated IOP was well maintained until 12 weeks. Topically administered agmatine powerfully lowered IOP to 30.29% of its pretreatment level, and the associated washout period was about two weeks. EVC was associated with a 55.44% loss of RGCs in the control group, but agmatine appeared to attenuate this RGC loss to 18.65%. Overall, topically administered agmatine appeared to effectively lower IOP and rescue RGCs in a chronic ocular hypertensive rat model. Although the mechanism underlying these effects is not yet established, it is possible that agmatine offers a powerful new ocular hypotensive agent for eyes with chronic ocular hypertension and/or glaucoma.
Hong
Samin
S
Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 712 Eonjuro, Gangnam-gu, Seoul 135-720, Republic of Korea.
Kim
Chan Yun
CY
Lee
Won Seok
WS
Shim
Jongwoo
J
Yeom
Ho Yeop
HY
Seong
Gong Je
GJ
D000287:Administration, Topical; D000376:Agmatine / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D002452:Cell Count; D002908:Chronic Disease; D004195:Disease Models, Animal; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage; D009798:Ocular Hypertension / Q000188:drug therapy*; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology
D000959:Antihypertensive Agents; D018696:Neuroprotective Agents; D009883:Ophthalmic Solutions; D000376:Agmatine