CYTOPROTECTION OF THE OCULAR SURFACE

Purpose. Development of new drugs for cytoprotection of the ocular surface.
Material and methods. In the course of standard experiments on the eyes of 15 healthy rabbits, we assessed the protective activity of newly developed drugs: ophthalmic drug films (ODF) with 6-methyl-3-(thietan-3-yl)uracil and ODF with methyluracil.
Results. An experimental study established their high therapeutic effect with pronounced cytoprotective, reparative and antiinflammatory activity compared to the control. The developed drugs can be used in ophthalmic practice in future. On the 2nd day, total desquamation of epithelial cells of the ocular surface, inflammatory cell infiltration with leukocytes, macrophages and lymphocytes in the limbal and perilimbal areas were noted. On the 7th day of using the ODF 6-methyl-3-(thietan-3-yl)uracil, the morphological picture was characterized by activation of proliferative processes. When using ODF with methyluracil, total epithelization of the ocular surface in the damaged area was revealed. In the control group, at the same time, the layer of epithelium crawled onto the collagen surface, inflammatory infiltrates, intercellular edema and signs of peeling of the epithelium were present. On the 14th day of the experiment, when treated with ODF 6-methyl-3-(thietan-3-yl)uracil, the stratified squamous non-keratinizing epithelium restored its structure. When treated with ODF with methyluracil, signs of proliferation were still observed. In the control, only a tendency towards complete restoration of the epithelial defect was observed. On the 21st day of the experiment using the ODF methyluracil, in contrast to the ODF 6-methyl-3-(thietan-3-yl)uracil, migration of epithelial cells in the form of epithelial ridges or proliferates was detected.
Conclusion. Ophthalmic drug films with 6-methyl-3-(thietan-3-yl)uracil and methyluracil experimentally proved a high therapeutic effect with pronounced cytoprotective, reparative and anti-inflammatory activity. The developed drugs based on 6-methyl-3-(thietan-3-yl)uracil can in future be used in ophthalmic practice as technologies for the pharmacological correction of ocular surface disorders induced by preservative antiglaucoma drugs.

1. Astakhov S.Yu., Tkachenko N.V. Taflotan, the first preservative-free prostaglandin F2α analogue: treatment advantages in primary open-angle glaucoma patients. Ophthalmology Journal, 2016;9(2):59-68. (In Russ.)

2. Brzhesky V.V., Radhuan M. Glaukoma i sindrom suhogo glaza (Glaucoma and dry eye syndrome). Ophthalmologicheskie vedomosti. 2014;7(2):37-49. (In Russ.)

3. Erichev V.P., Petrov S.I., Volzhanin A.V. [et al.]. Continuous anti-glaucoma drug therapy as a risk factor of dry eye. Vestnik Oftalmologii. 2019;135(6):117-123. (In Russ.)

4. 6-metil-1-(tietanil-3)uracil, stimulirujushhij zashhitnuju aktivnost' fagocitov (6-methyl-1-(thietanyl-3)uracil, stimulating the protective activity of phagocytes): patent № 2485118 Ros. Federacija; zajavl. 03.05.2012; opubl. 20.06.2013. Bjul. № 17:6. (In Russ.)

5. Obenberger J. Paper strips and rings as simple tools for standartization of experimental eye injuries. Ophthalmol. Res. 1975; 7:363-366. (in Engl)

6. Gabdrakhmanova A.F. [et al.] New Drugs for Ophthalmology Based on 6-methyl-3-(thietan-3-yl)uracil (Experimental Research). Ophthalmology in Russia. 2021;18(2):355–360. (In Russ.) https://doi.org/10.18008/1816-5095-2021-2-355-360.