A.A. Dementyeva - Student, Faculty of Fundamental Medicine, Lomonosov Moscow State University. E-mail: a.dementyeva@yandex.ru A.A. Kibitov - Student, Faculty of Fundamental Medicine, Lomonosov Moscow State University A.K. Erdiakov - Post-graduate Student, Faculty of Fundamental Medicine, Lomonosov Moscow State University A.V. Balatskii - Ph.D. (Med.), Junior Research Scientist, Laboratory of Medicine Physician, Medical Scientific and Educational Center, Lomonosov Moscow State University S.A. Gavrilova - Ph.D. (Biol.), Associate Professor, Faculty of Fundamental Medicine, Lomonosov Moscow State University

Provocation of intraocular inflammation is accompanied with redundant prostaglandins production, which can aggravate the following period of inflammation by effecting cyclooxygenases (COXs) production by positive feedback mechanism. Cur-rently this connection in eye and retina is not known. Eye of Wistar rat was injected with 0,5 mcg (2 mcl) ConA in vitreous cavity. After 20 min rats received a saline, 16 mcg lornoxicam or 80 mcg triamcinolone intravitreal (i/v) injection (2 mcl). On 1 and 2 day after that the medication was admi-nistered systemically. We also used intact control group. Immunohistochemistry (using antibodies for COX-1 and COX-2) evaluation of retinas was made on 1st, 3d, 7th, 14th, 28th and 56th days after i/v injection of ConA. We also measured le-vels of COX-1, COX-2, PGD2S and PGE2S mRNAs in vitreoretinal blocks with real-time RT-PCR. COX-2 mostly involved in the process of intaocular inflammation. We see the reduction of COX-2 levels in different retina layers in treatment groups during the acute phase of inflammation. For the first time we have shown that inhibition of total arachidonic acid metabolism as well as cyclooxygenase pathway prevents the increase in COX-2 production on the 1st day of intraocular inflammation. It means that prostaglandines branch of arachidonic acid metabolism is likely to influence on COX-2 production by positive feedback mechanism. After the 7th day of inflammation both drugs keep COX-2 production on intact group level, as long as in group without cure COX-2 production in nuclear layers dramatically decreased. Administration of drugs at the moment of inflammation initiation effects COX-2 production in both acute and chronical phases. It confirms that changes in inflammatory process depends on drugs administration. Total mRNAs expression of COX-1 and COX-2 genes by vitreoretinal blocks is slightly different between experimental groups compared to the production of these proteins by different retina layers. It emphasizes the meaningful participation of vitreoretinal interface in the autoregulation of intraocular inflammation. Nevertheless we see that total profile of COXs and prostaglandins mRNA expression varies depending on the experimental group and day of experiment.

 

1. Vichai V., Suyarnsesthakorn C., Pittayakhajonwut D., Sriklung K., Kirtikara K. Positive feedback regulation of COX-2 expression by prostaglandin metabolites // Inflammation Research. 2005. V. 54. P. 163-172.
2. Erdjakov A.K., Tikhonovich M.V., Rzhavina E.M., Gavrilova S.A. KHarakteristiki setchatki pri razvitii proliferativnojj vitreo­re­ti­no­patii u krys posle vnutriglaznojj inekcii konkanavalina A i dispazy // Rossijjskijj fiziologicheskijj zhurnal im. I.M. Sechenova. 2015. T. 101. № 5. S. 572-585.
3. Radi Z.A., Render J.A. The Pathophysiologic Role of Cyclo-Oxygenases in the Eye // Journal of Ocular Pharmacology and Therapeutics. 2008. V. 24. № 2. P. 141-151.
4. Gilroy D.W., Colville-Nash P.R., Willis D., Chivers J., Paul-Clark M.J., Willoughby D.A. Inducible cyclooxygenase may have anti-inflam­matory properties // Nature Medicine. 1999. V. 5. № 6. P. 698-701.
5. Chennamaneni S.R., Bohner A., Bernhisel A., Ambati B.K. Pharmacokinetics and Efficacy of Bioerodible Dexamethasone Implant in Concanavalin A-induced Uveitic Cataract Rabbit Model // Pharm Res. 2014. V. 31. № 11. P. 3179-3190.
6. Gwon A., Mantras C., Gruber L., Cunanan C. Concanavalin A-Induced Posterior Subcapsular Cataract: A New Model of Cataractogenesis // Investigative Ophthalmology & Visual Science. 1993. V. 34. № 13. P. 3483-3488.
7. Er H., Uzmez E., Dogan N., Cumhurcu T. The Anti-inflammatory Effects of NG-Nitro L-Argi­nine (L-NAME) and Steroid in Concanavalin A-Induced Uveitis // Tr. J. of Medical Sciences. 1999. V. 29. P. 233-236.
8. Baneke A.J., Lim K. Sheng, Stanford M. The Pathogenesis of Raised Intraocular Pressure in Uveitis // Current Eye Research, Early Online. 2015. P. 1-13.
9. Maihofner C., Schlotzer-Schrehardt U., Guhring H., Zeilhofer H.U., Naumann G., Pahl A., Mardin C., Tamm E., Brune K. Expression of Cyclo­oxygen­nase-1 and -2 in Normal and Glaucomatous Human Eyes // IOVS. 2001. V. 42. № 11.
10. Kaufmann U., Diedrichs-Mohring M., Wildner G. Dynamics of Intraocular IFN-g, IL-17 and IL-10-Producing Cell Populations during Relapsing and Monophasic Rat Experimental Autoimmune Uveitis // PLOS ONE. 2012. V. 7. P. 1-11.
11. Deng W-G., Alberto J., Monter A.J., Wu K.K. Interferon-γ Suppresses Cyclooxygenase-2 Promoter Activity by Inhibiting C-Jun and C/EBPβ Binding // Arterioscler Thromb Vasc Biol. 2007. V. 27. P. 1752-1759.
12. Barrios-Rodiles M., Chadee K. Novel Regulation of Cyclooxygenase-2 Expression and Prostaglan-din E 2 Production by IFN- γ in Human Macrophages // The Journal of Immunology. 1998. V. 161. P. 2441-2448.
13. Takai E., Tsukimoto M., Kojima S. TGF-β1 Downregulates COX-2 Expression Leading to Decrease of PGE2 Production in Human Lung Cancer A549 Cells, Which Is Involved in Fibrotic Response to TGF-β1 // PLOS ONE. 2013. V. 8. P. 1-13.
14. Kapin M.A., Yanni J.M., Brady M.T., McDonough T.J., Flanagan J.G., Rawji M.H., Dahlin D.C., Sanders M.E., Gamache D.A. Inflammation-Mediated Retinal Edema in the Rabbit Is Inhibited by Topical Nepafenac // Inflammation. 2003. V. 27. № 5. P. 281-291.
15. Brock T.G., McNish R.W., Peters-Golden M. Arachidonic Acid Is Preferentially Metabolized by Cyclooxygenase-2 to Prostacyclin and Prosta­glan­din E2 // The Journal Of Biological Chemistry. 1999. V. 274. № 17. P. 11660-11666.
16. Zilfjan A.A. Sdvigi v soderzhanii prosta­glan­dinov E2 vo vnutriglaznojj  zhidkosti pacientov s senilnymi i oslozhnennymi kataraktami // Oftalmokhirurgija. 2013. № 3. S. 86-90.
17. Gerashchenko D., Beuckmann C.T., Kanaoka Y., Eguchi N., Gordon W.C., Urade Y., Bazan N.G., Hayaishi O. Dominant Expression of Rat Pros­tanoid DP Receptor mRNA in Leptomeninges, Inner Segments of Photoreceptor Cells, Iris Epithelium, and Ciliary Processes // Journal of Neurochemistry. 1998. V. 71. P. 937-945. 
18. Gerashchenko D., Beuckmann C.T., Marcheselli V.L., Gordon W.C., Kanaoka Y., Eguchi N., Urade Y., Hayaishi O., Bazan N.G. Localization of Lipocalin-Type Prostaglandin D Synthase (Trace β) in Iris,Ciliary Body, and Eye Fluids // IOVS. 1998. V. 39. № 1. P. 198-203.
19. Hirai H., Tanaka K., Yoshie O., Ogawa K., Kenmotsu K., Takamori Y., Ichimasa M., Sugamura K., Nakamura M., Takano S., Nagata K. Prostaglandin D2 Selectively Induces Chemotaxis in T Helper Type 2 Cells, Eosinophils, and Basophils via Seven-Transmembrane Receptor CRTH2 // J. Exp. Med. 2001. V. 193. № 2. P. 255-261.
20. Goh Y., Nakajima M., Azuma I, Hayaisht O. Prostaglandin D2 reduces intraocular pressure // British Journal of Ophthalmology. 1988. V. 72. P. 461-464.