Pharmacologic intervention targeting glycolytic-related pathways protects against retinal injury due to ischemia and reperfusion.
Retinal ischemia contributes to multiple ocular diseases while aminoguanidine (AMG) treatment significantly inhibits the neuronal and vascular degeneration due to acute retinal ischemia and reperfusion (I/R) injury. In the present study, 2-D DIGE was applied to profile global protein expression changes due to retinal I/R injury, and the protection effects mediated by AMG. Retinal ischemia was induced by elevated intraocular pressure to 80-90 mmHg for 2 h, and reperfusion was established afterward. Retinal tissues were collected 2 days after I/R injury. After 2-D DIGE analysis, a total of 96 proteins were identified. Among them, 28 proteins were identified within gel spots whose intensities were normalized by AMG pretreatment, pathway analysis indicated that most were involved in glycolysis and carbohydrate metabolism. Selected enzymes identified by MS/MS within these pathways, including transketolase, triosephosphate isomerase 1, aldolase C, total enolase, and pyruvate kinase were validated by quantitative Western blots. Glycolytic enzymes and other differentially regulated proteins likely play previously unrecognized roles in retinal degeneration after I/R injury, and inhibition of the resulting metabolic changes, using pharmacologically agents such as AMG, serve to inhibit the changes in metabolism and mitigate retinal degeneration. Select glycolytic enzymes may provide novel therapeutic targets for inhibiting the neuronal and vascular degeneration after retinal I/R injury.
Zheng
Ling
L
College of Life Sciences, Wuhan University, Wuhan, PR China. lzheng217@hotmail.com
Liu
Shuqing
S
Sun
Ming-Zhong
MZ
Chang
Jinsook
J
Chance
Mark R
MR
Kern
Timothy S
TS
D000704:Analysis of Variance; D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006019:Glycolysis / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D018917:Optic Neuropathy, Ischemic / Q000378:metabolism*; D011506:Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism*; D015203:Reproducibility of Results; D012164:Retinal Diseases / Q000378:metabolism*; D018709:Statistics, Nonparametric; D053719:Tandem Mass Spectrometry
D004791:Enzyme Inhibitors; D006146:Guanidines; D011506:Proteins; C004479:pimagedine