title: Akt is activated via insulin/IGF-1 receptor in rat retina with episcleral vein cauterization.
abstract: The Akt serine/threonine kinase mediates pro-survival signalings in retina and was reported to be activated in a response to some retinal and optic nerve injuries. Human and experimental glaucoma induce apoptosis of retinal ganglion cells (RGCs). The purpose of this study is to test whether episcleral vein cauterization (EVC) to chronically elevate intraocular pressures (IOPs) in rats increase apoptosis of RGCs and affect activation of Akt and its upstream insulin-like growth factor (IGF)-1 receptor/Insulin receptor. Three episcleral veins in left eyes of Sprague-Dawley rats were cauterized to elevate IOPs. Up to 6 months, IOPs were monitored and the retina was dissected at several time points. The numbers of terminal dUTP nick end labeling (TUNEL)-positive cells and those of RGCs labeled with fluorogold were counted in flat-mounted retina. Immunohistochemistry and immunoblotting were performed to identify cells expressing phosphorylated Akt and to quantify the phospho- to total ratios of Akt and IGF-1 receptor/insulin receptor. EVC significantly elevated IOPs up to 2 months, increased TUNEL-positive cells in an IOP-dependent fashion, and reduced 34.5% of RGCs at 6 months (P<0.001) compared with contralateral retinas. Phosphorylated Akt was specifically expressed in RGCs until 1 month after cauterization. Akt (P=0.036) and IGF-1 receptor/Insulin receptor (P=0.003) were transiently phosphorylated at 3 days. Intrinsic activation of the IGF-1 receptor/Insulin receptor to Akt pathway may occur in RGCs in retina with EVC.
authors.affiliation: Department of Organ Therapeutics, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Akiyasu
authors.initials: A
authors.lastname: Kanamori
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Azusa
authors.initials: A
authors.lastname: Nagai
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Mukuno
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Akira
authors.initials: A
authors.lastname: Negi
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002058:Burns, Electric / Q000150:complications / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D016923:Cell Death / Q000502:physiology / Q000528:radiation effects; D004195:Disease Models, Animal; D004789:Enzyme Activation; D007839:Functional Laterality; D005901:Glaucoma / Q000209:etiology / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007328:Insulin / Q000378:metabolism*; D007429:Intraocular Pressure / Q000502:physiology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D012590:Sclera / Q000098:blood supply / Q000473:pathology; D013266:Stilbamidines; D013997:Time Factors; D014680:Veins / Q000293:injuries
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D007328:Insulin; C490546:Map1a protein, rat; D008869:Microtubule-Associated Proteins; D013266:Stilbamidines; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt