Retinal ischemic injury rescued by sodium 4-phenylbutyrate in a rat model.
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.
Jeng
Yung-Yue
YY
Graduate Institute of Veterinary Medicine, College of Bio-resources and Agriculture, National Taiwan University, Taipei, Taiwan.
Lin
Nien-Ting
NT
Chang
Pen-Heng
PH
Huang
Yuan-Ping
YP
Pang
Victor Fei
VF
Liu
Chen-Hsuan
CH
Lin
Chung-Tien
CT
D000818:Animals; D002452:Cell Count; D016923:Cell Death; D004305:Dose-Response Relationship, Drug; D005901:Glaucoma / Q000150:complications / Q000188:drug therapy; D007511:Ischemia / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D010654:Phenylbutyrates / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D012164:Retinal Diseases / Q000188:drug therapy* / Q000209:etiology; D012165:Retinal Ganglion Cells / Q000473:pathology; D012171:Retinal Vessels / Q000473:pathology
D010654:Phenylbutyrates; C075773:4-phenylbutyric acid