

Development of criteria for a comprehensive assessment of the effectiveness of antiangiogenic drugs on models of neovascularization of the eye (experimental studies)
https://doi.org/10.33791/2222-4408-2022-3-39-47
Abstract
The evolution of therapeutic technologies dictates the development of a strategy for their implementation in clinical practice. The first stage is the assessment of the capabilities, efficiency, advantages and disadvantages, development of indications and contraindications on models of eye diseases in the experiment.
The purpose of the work: to develop criteria for assessing the effectiveness of anti‑angiogenic drugs and evaluate the proposed modeland neovascularization of the eye in the experiment.
Materials and methods. Neoangiogenesis models – two chorioretinal and two corneal localizations – were formed in the experiment on rabbits of Sovetskaya Chinchilla breed. The advantages and disadvantages of each of them were analyzed empirically. Experimental animals with neovascular disease were treated with recombinant peptides with angiostatic potential (tumstatin, PEDF, endostatin). In the course of treatment, we developed efficacy criteria based on clinical, instrumental, and morphological studies.
Results. Comprehensive efficacy evaluation criteria were developed and tested, allowing not only to reveal and describe the spectrum of biological effects of the tested drugs, but also to quantitatively assess and compare their therapeutic potential with each other at almost all stages of vascular assembly. The complex consisted of qualitative and quantitative clinical (hyperemia, edema, vascularization, antiangiogenic activity according to a score scale), angiographic (intensity and area of edema, area of neovascularization and index of corneal vascularization) and morphological (extent of edema, extent of vessels and their number in section, index of vascularization) indicators.
Conclusion. To get the full amount of information about the tested drug with the claimed angiostatic potential, it is necessary to use several models of neoangiogenesis with different mechanisms to study the amplitude and spectrum of their effects.
About the Authors
V. G. LikhvantsevaRussian Federation
Vera G. Likhvantseva, Dr. Sci. (Med.), Professor of Academy of Postgraduate Education; Senior Researcher of the Scientific Department, Laboratory 13
15, Gamalei Str., Moscow, 123098, Russian Federation
91, Volokolamskoe Highway, Moscow, 125371, Russian Federation
A. S. Gevorgyan
Russian Federation
Armine S. Gevorgyan, Applicant for the Department of Ophthalmology of the Academy of Postgraduate Education
91, Volokolamskoe Highway, Moscow, 125371, Russian Federation
S. G. Kapkova
Russian Federation
Svetlana G. Kapkova, Cand. Sci. (Med.), Head of the Ophthalmology Department of the Center of Ophtalmology; Associate Professor of the
Academy of Postgraduate Education
15, Gamalei Str., Moscow, 123098, Russian Federation
91, Volokolamskoe Highway, Moscow, 125371, Russian Federation
K. A. Kuzmin
Russian Federation
Kirill A. Kuzmin, participant in the experiment, histomorphologist
5, 2nd Botkinsky Lane., Moscow, 125284, Russian Federation
A. I. Miroshnikov
Russian Federation
Anatoly I. Miroshnikov, Academician of the Russian Academy of Sciences, Dr. Sci. (Chem.), Head of the Department of Biotechnology
16/10, Miklouho-Maclaya Str., 117997, Moscow, Russian Federation
R. S. Esipov
Russian Federation
Roman S. Esipov, Dr. Sci. (Chem.), Head of the Laboratory of Biopharmaceutical Technologies of the Department of Biotechnology
16/10, Miklouho-Maclaya Str., 117997, Moscow, Russian Federation
References
1. Passaniti A., Taylor R.M., Pili R., Guo Y. et al. A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor. Lab Invest. 1992;67(4):519–28.
2. Passaniti A., Kleinman H.K., Martin G.R. Matrigel: history/background, uses, and future applications. J Cell Commun. Signal. 2021;Aug 31. https://doi.org/10.1007/s12079-021-00643-1
3. Miller H., Miller B., Ishibashi T., Ryan S.J. Pathogenesis of laser-induced choroidal subretinal neovascularization. Invest Ophthalmol Vis Sci. 1990;31(5):899–908.
4. Miller J.W., Adamis A.P., Shima D.T. et al. Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am J Pathol. 1994;145(3):574–584.
5. Marey M.V., Nikolaeva L.R., Poltavtseva R.A., Sukhikh G.T., Chentsova E.V. Stem cell transplantation for corneal burns in the experiment. RMJ. Clinical Ophthalmology. 2005;6(4):150–152. (In Russ.)
6. Andreev Yu.V., Kopayeva V.G. Development of a new technology for photodynamic destruction of newly formed corneal vessels based on the local introduction of photosensitizers. Bullet Ophthalm. 2005;5:21–25. (In Russ.)
7. Aznauryan I.E., Shpak A.A., Balasanyan V.O., Kudryashova E.A. Comparison of Suture material Vicryl 6-0 and 7-0 for strabismus surgery by strength characteristics of the suture. Ophthalmosurgery. 2018;2:63–66. (In Russ.) https://doi.org/10.25276/0235-4160-2018-2-63-66
8. Cartmill B.T., Parham D.M., Strike P.W. et al. How do absorbable sutures absorb? A prospective doubleblind randomized clinical study of tissue reaction to polyglactin 910 sutures in human skin. Orbit. 2014;33(6):437–443. https//doi.org/10.3109/01676830.2014.950285
9. Iwata T., Tomarev S. Animal models for eye diseases and therapeutics. Sourcebook of models for biomedical research. 2008:279–287. https//doi.org/10.1007/978-1-59745-285-4_31
10. Likhvantseva V.G., Gevorkyan A.S., Kapkova S.G. Comparative aspects of experimental models of neovascularization of the eyes of different localization (experimental studies). The EYE GLAZ. 2022;24(2):32–46. (In Russ.) https://doi.org/10.33791/2222-4408-2022-2-32-46
11. Guidelines for conducting preclinical studies of medicines. Part 1. Mironov A.N., ed. Moscow: Grif i K, 2013. 944 p. (In Russ.)
12. Guide to the experimental (preclinical) study of new pharmacological substances. Under the general editorship of the corresponding member of the Russian Academy of Medical Sciences, professor R.U. Khabriev. 2nd ed., rev. and add. Moscow: Publishing House “Medicine”, 2005. 832 p. (In Russ.)
Review
For citations:
Likhvantseva V.G., Gevorgyan A.S., Kapkova S.G., Kuzmin K.A., Miroshnikov A.I., Esipov R.S. Development of criteria for a comprehensive assessment of the effectiveness of antiangiogenic drugs on models of neovascularization of the eye (experimental studies). The EYE GLAZ. 2022;24(3):39-47. (In Russ.) https://doi.org/10.33791/2222-4408-2022-3-39-47