KR-31378, a potassium-channel opener, induces the protection of retinal ganglion cells in rat retinal ischemic models.
KR-31378 is a newly developed K(ATP)-channel opener. To investigate the ability of KR-31378 to protect retinal ganglion cells (RGC), experiments were conducted using two retinal ischemia models. Retinal ischemia was induced by transient high intraocular pressure (IOP) for acute ischemia and by three episcleral vein occlusion for chronic retinal ischemia. KR-31378 was injected intraperitoneally and administered orally in the acute and chronic ischemia models, respectively. Under the condition of chronic ischemia, RGC density in the KR-31378-treated group was statistically higher than that in the non-treated group, and IOP was reduced. In the acute retinal ischemia model, 90% of RGC were degenerated after one week in non-treated retina, but, RGC in KR-31378-treated retina were protected from ischemic damage in a dose-dependent manner and showed inhibited glial fibrillary acidic protein (GFAP) expression. Furthermore, the KR-31378 protective effect was inhibited by glibenclamide treatment in acute ischemia. These findings indicate that systemic KR-31378 treatment may protect against ischemic injury-induced ganglion cell loss in glaucoma.
Department of Ophthalmology and Visual Science, College of Medicine and Korean Eye and Gene Bank Related to Blindness, The Catholic University of Korea, Seoul, Korea.
Anho
A
Choi
Jun-Sub
JS
Choi
Yone-Jung
YJ
Yoon
Kyung-A
KA
Kim
Choun-Ki
CK
Joo
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005901:Glaucoma / Q000188:drug therapy / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000187:drug effects; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D009798:Ocular Hypertension / Q000188:drug therapy / Q000473:pathology; D015221:Potassium Channels / Q000819:agonists*; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D012171:Retinal Vessels / Q000187:drug effects*
D005904:Glial Fibrillary Acidic Protein; D006146:Guanidines; C438686:N''-cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2H-benzopyran-4-yl)-N'-benzylguanidine; D015221:Potassium Channels; D011714:Pyrans