Abstract
Abstract: :
Purpose: Chronically elevated intraocular pressure (IOP) leads to apoptotic processes in retinal ganglion cells (RGCs). However, intrinsic counter–apoptotic mechanisms have not been fully investigated. The purpose of this study is to test whether Akt, a main intracellular pro–survival mediator, is activated in rat retina with chronic IOP elevation. Methods: A chronically elevated IOP model was produced by cauterization of three episcleral veins in unilateral eyes of Sprague–Dawley rats. IOPs were monitored with Tonopen®.The retinas were dissected at several time points up to 6 months. The whole mount retinas were subjected to terminal dUTP nick end labeling (TUNEL) or immunofluoresence for Akt or mitogen activated protein kinase (MAPK). The retinal homogenates were also immunoblotted for phosphorylated and total Akt, MAPK, or IGF–1 receptor/ insulin receptor. Results: IOP was elevated by the cauterization up to 2 months. TUNEL positive cells were significantly increased and then reversed over time in an IOP–dependent fashion. Immunoreactivity against Akt phosphorylated at Ser 473, but not MAPK, was increased in RGC bodies and dendrites or axons 3 days, 2 weeks, and 1 month, but not thereafter. Immunoblotting also revealed that phospho to total Akt, but not MAPK, was significantly elevated at 3 days, which accompanied the increased phosphorylation of IGF–1 receptor/insulin receptor. Conclusions: Akt is phosphorylated in rat retina in an IOP–dependent fashion, which may be an intrinsic counter–apoptotic cascade.
Keywords: ganglion cells • intraocular pressure • apoptosis/cell death