Differential modulation of MAPKs in relation to increased intraocular pressure in the aqueous humor of rat eye injected with hyaluronic acid.
OBJECTIVE
To explore the presence of several mitogem-activated protein kinases in the aqueous humor and to follow changes in levels and activity along chronic elevated intraocular pressure.


METHODS
Intra-anterior chamber once-a-week injections of hyaluronic acid were used as a rat model of induced elevated intraocular pressure. Saline-injected rats served as control and the counter untreated eye was used as sham group. Aqueous humor was taken at different timepoints and analyzed by Western blot analysis for Erk, JNK, AP1, and NOS in the phosphorylated active form and total protein expression.


RESULTS
Phosphorylated Erk was detected in the aqueous humor of the entire tested groups. In rats exposed to elevated intraocular pressure for longer than two weeks, a significant increase in the Erk activation was found. Total Erk expression following the hyaluronic acid injections significantly increased. Higher incidence of phosphorylated 46kD JNK was found in the aqueous humor of the hyaluronic acid injection (63%) versus the saline and sham groups (43%). Rats with elevated intraocular pressure after two weeks expressed significantly higher pJNK than the short-term injected hyaluronic acid, saline, and sham groups. The amount of the two JNK isomers declined in the hyaluronic acid injected rats, reaching significance when the elevated intraocular pressure is longer than two weeks versus sham. Among the tested samples, 74% expressed the different NOS isoforms independent of the treatment. Along with the "non responders," the majority were from the sham group. There is a significant decrease in the total amount of the three isoforms in the hyaluronic acid injected rats after two weeks versus the sham and saline groups.


CONCLUSIONS
We suggest that these signaling molecules might be a new target for intervention, opening new possibilities for intraocular pressure management.
Shmulevich
Alla
A
Clinical Pharmacology Department, The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Beit-Yannai
Elie
E
D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects; D001082:Aqueous Humor / Q000201:enzymology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007267:Injections; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009798:Ocular Hypertension / Q000139:chemically induced / Q000201:enzymology*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D014065:Tonometry, Ocular
D006820:Hyaluronic Acid; D020928:Mitogen-Activated Protein Kinases