Abstract
Purpose
This study proves the possibility of targeted use of the nonsteroidal anti-inflammatory drug lornoxicam to prevent the development of proliferative vitreoretinopathy (PVR). Triamcinolone acetonide (TA) was selected as a reference substance.
Methods
Wistar rats (N = 400) were used. PVR was modeled by intravitreal injection of dispase or concanavalin A. Lornoxicam or TA intravitreal administration was performed 20 min later. On the second and the third day, drugs were administrated systemic. Enucleation was performed on the first, third, seventh and 42nd or 56th day of the experiment.
Results
Pro-inflammatory substances led to the development of sub- and epiretinal membranes. Lornoxicam decreased the incidence of membrane formation by 43 and 31% in dispase and concanavalin models, respectively. Membranes, formed during its use, were smaller and contained less fibrotic components. At the end of the experiment, the thickness of retinal and choroidal layers among the animals which had received the therapy was the same as the thickness of the retina and choroid of intact rats. Lornoxicam administration normalized the cyclooxygenases (COXs) expression in the retina and the choroid at the early stages of the experiment. TA application was less effective in both models.
Conclusions
COXs blocking during the development of PVR, overwhelming inflammation in the eye and reducing its consequences, is proved to be a much more effective and safe influence than the suppression of the entire cascade of arachidonic acid metabolism. Lornoxicam did not only improve the condition of the retina and the choroid but also significantly reduced the frequency of membrane formation.
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Acknowledgements
We thank A.A. Dementyeva and A.A. Kibitov for help in obtaining some of the immmunohistochemical results.
Funding
This work was supported by Russian Foundation for Basic Research grant (No. 14-04-01318-A). The funding organization had no role in the design or conduct of this research.
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Tikhonovich M. has a patent RU2558991 licensed to Lomonosov Moscow State University, and a patent RU2458656 licensed to The S.N. Fyodorov “Eye microsurgery” Federal State Institution. Erdiakov A. has a patent RU2563368 licensed to Lomonosov Moscow State University. Gavrilova S. has a patent RU2563368 licensed to Lomonosov Moscow State University, and a patent RU2558991 licensed to Lomonosov Moscow State University.
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All applicable international, national and/or institutional guidelines for the care and use of animals were followed.
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Tikhonovich, M.V., Erdiakov, A.K. & Gavrilova, S.A. Nonsteroid anti-inflammatory therapy suppresses the development of proliferative vitreoretinopathy more effectively than a steroid one. Int Ophthalmol 38, 1365–1378 (2018). https://doi.org/10.1007/s10792-017-0594-3
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DOI: https://doi.org/10.1007/s10792-017-0594-3