Retinal ischemic injury rescued by sodium 4-phenylbutyrate in a rat model
Journal
Experimental Eye Research
Journal Volume
84
Journal Issue
3
Pages
486-492
Date Issued
2007
Author(s)
Abstract
Retinal ischemia is a common cause of visual impairment for humans and animals. Herein, the neuroprotective effects of phenylbutyrate (PBA) upon retinal ischemic injury were investigated using a rat model. Retinal ganglion cells (RGCs) were retrograde labeled with the fluorescent tracer fluorogold (FG) applied to the superior collicoli of test Sprague-Dawley rats. High intraocular pressure and retinal ischemia were induced seven days subsequent to such FG labeling. A dose of either 100 or 400 mg/kg PBA was administered intraperitoneally to test rats at two time points, namely 30 min prior to the induction of retinal ischemia and 1 h subsequent to the cessation of the procedure inducing retinal ischemia. The test-rat retinas were collected seven days subsequent to the induction of retinal ischemia, and densities of surviving RGCs were estimated by counting FG-labeled RGCs within the retina. Histological analysis revealed that ischemic injury caused the loss of retinal RGCs and a net decrease in retinal thickness. For PBA-treated groups, almost 100% of the RGCs were preserved by a pre-ischemia treatment with PBA (at a dose of either 100 or 400 mg/kg), while post-ischemia treatment of RGCs with PBA did not lead to the preservation of RGCs from ischemic injury by PBA as determined by the counting of whole-mount retinas. Pre-ischemia treatment of RGCs with PBA (at a dose of either 100 or 400 mg/kg) significantly reduced the level of ischemia-associated loss of thickness of the total retina, especially the inner retina, and the inner plexiform layer of retina. Besides, PBA treatment significantly reduced the ischemia-induced loss of cells in the ganglion-cell layer of the retina. Taken together, these results suggest that PBA demonstrates a marked neuroprotective effect upon high intraocular pressure-induced retinal ischemia when the PBA is administered prior to ischemia induction. ? 2006 Elsevier Ltd. All rights reserved.
SDGs
Other Subjects
4 phenylbutyric acid; fluorogold; animal experiment; animal model; article; cell labeling; cell loss; cell survival; controlled study; disease model; intraocular pressure; male; nerve cell; neuroprotection; nonhuman; priority journal; rat; retina ganglion cell; retina ischemia; Animals; Cell Count; Cell Death; Dose-Response Relationship, Drug; Glaucoma; Ischemia; Male; Microscopy, Fluorescence; Models, Animal; Phenylbutyrates; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Retinal Diseases; Retinal Ganglion Cells; Retinal Vessels
Type
journal article