Suppression of rat retinal ganglion cell death by PACAP following transient ischemia induced by high intraocular pressure.
Glaucoma is a neurodegenerative disease in which increasing intraocular pressure leads to the progressive loss of retinal ganglion cells (RGCs) and blindness. Here, we report a neuroprotective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) against RGC loss induced by high intraocular pressure in the rat. Vehicle or PACAP (1 fM to 1,000 pM) solution was injected into the vitreous body once after induction of a high intraocular pressure (110 mmHg). Seven days later, the number of viable RGCs was reduced to 45% of that in the intact control. However, PACAP treatment significantly reduced this RGC death in a bimodal manner, with peaks at 10 fM and 10-100 pM. The cAMP antagonist Rp-cAMP significantly blocked the neuroprotective effect of PACAP at both high and low doses, whereas the MAP kinase inhibitor PD-98059 only prevented the effect of the low dose of PACAP. These findings suggest that PACAP has bimodal effects in the neuroprotection of RGCs against ischemia and that these effects are mediated via different signaling pathways.
Seki
Tamotsu
T
Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
Itoh
Hiroyuki
H
Nakamachi
Tomoya
T
Endo
Kimi
K
Wada
Yoshihiro
Y
Nakamura
Keisuke
K
Shioda
Seiji
S
D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007429:Intraocular Pressure; D007511:Ischemia / Q000209:etiology*; D008297:Male; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology*; D013873:Thionucleotides / Q000494:pharmacology
D005419:Flavonoids; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D047428:Protein Kinase Inhibitors; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one