Effects of L-NAME and timolol on aqueous IL-1beta, IL-6, IL-8, TNF-alpha and NO levels after Nd:YAG laser iridotomy in rabbits.
OBJECTIVE
Pro-inflammatory cytokines are produced by tissues and play a vital role in the host inflammatory response and uveitis. Nitric oxide (NO) can be produced in large amounts as a response to experimentally-induced uveitis or cytokines. In this study, we measured the levels of pro-inflammatory cytokines such as interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha and free-radical in aqueous humor after Nd:YAG laser iridotomy in rabbits, and investigated whether timolol maleate an anti-glaucoma drug, or a NO synthase inhibitor, NG-nitro-L-arginine methyl esther (L-NAME) had an inhibitory effect on these molecules, since L-NAME is a known anti-inflammatory agent in rabbits.


METHODS
Bilateral experimental Nd:YAG laser iridotomy (power 7.5 mJ, mode single burst, aiming beam 4) was performed on 18 rabbits under general plus topical anesthesia. Aqueous humor samples were taken by clear corneal paracentesis preoperatively, and 1 and 24 h postoperatively. Six rabbits (12 eyes) were given bilateral topical timolol maleate 0.5% (Timoptic) drop b.i.d. (group 1), six rabbits (12 eyes) received bilateral 0.1 ml subconjuntival injections of L-NAME (150 mg/kg) (group 2), and six rabbits (12 eyes) were treated with topical balanced salt solution (BSS) b.i.d. (control). RESULTS. Preoperative cytokine and NO levels were comparable in the three groups, with no significant differences. In addition, there was no significant difference in baseline cytokine levels between the right and left eyes. In all groups, pre- and postoperative mean IL-1beta levels were below the detection limit of the assay (<5.0 pg/ml). In the control group, postoperative mean IL-6, IL-8 and NO levels were significantly higher after Nd:YAG laser iridotomy than before (for each, p < 0.01). Timolol and L-NAME both inhibited the rise in IL-8 and TNF-alpha levels. Timolol also inhibited the rise in IL-6 but not NO. L-NAME had an inhibitory effect against NO, but not IL-6.


CONCLUSIONS
L-NAME has an inhibitory effect on IL-8, TNF-alpha and NO, but not on IL-6. Timolol had inhibitory effects on IL-6, IL-8 and TNF-alpha, but not on NO. These preliminary experimental results might help in assssing the effect of Nd:YAG laser iridotomy in aqueous humor, and to understand the inhibitory effects of timolol and L-NAME against these molecules.
Er
H
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Department of Ophthalmology, Inonu University School of Medicine, Turgut Ozal Medical Center, Malatya, Turkey. hamdier@inonu.edu.tr
Doganay
S
S
Evereklioglu
C
C
Cekmen
M
M
Daglioglu
M C
MC
Isci
N
N
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007498:Iris / Q000601:surgery*; D053685:Laser Therapy; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D011817:Rabbits; D013999:Timolol / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D013999:Timolol; D019331:NG-Nitroarginine Methyl Ester