The Protective Effect of Para-Aminobenzoic Acid in HypoxiaInduced Apoptosis of Conjunctiva and Cornea Cells in vivo
https://doi.org/10.18008/1816-5095-2021-2-317-324
Abstract
Purpose: to evaluate the effects of acute hypoxic hypoxia on eye tissue cells in adult rats and determining the effectiveness of 0.007 % solution of para-aminobenzoic acid (PABA) for apoptotic damage to the tissues of the ocular surface in rats.
Materials and methods. In the experiment, 27 male Wistar rats (54 eyes) were used, divided into 5 groups. Group I — intact control, Group II — hypoxic control after 1 hour, Group III — hypoxic control after 3 hours, Group IV — with the injection of the drug 1 hour after hypoxia, Group V — injection of the drug 24 hours before hypoxia. The identification of apoptotic cells in the tissues of the eye was performed by the TUNEL method on frozen sections of the eye stained with Hoechst 33342 nuclear fluorescent dye. The localization and fluorescence intensity of the damaged cells was analyzed under a fluorescence microscope using the Image J. computer program.
Results. Under the conditions of simulated acute hypoxic hypoxia, apoptotic lesions of the conjunctiva, corneal epithelium, choroid, and photoreceptor layer of the retina were observed. In group II, the number of damaged cells in the conjunctiva was 67 %, and in group III it was 120 % more compared to group I — the norm (p < 0.05). With the injection of PABA before hypoxia, there were no significant differences compared with the norm (group I) in the state of the affected cells in the conjunctiva. In the group of animals (group III) with the injection of PABA after hypoxia after 1 h, the number of damaged cells does not statistically differ from group II (hypoxic control after 1 h), but significantly lower than in group III (hypoxic control after 3 hours). The same pattern is observed in the corneal epithelium.
Conclusion. Para-aminobenzoic acid (0.007 %) has a prophylactic and therapeutic effect, preventing and stabilizing the development of apoptosis of conjunctival cells and anterior corneal epithelium induced in experimental acute hypoxic hypoxia.
About the Authors
A. A. RyabtsevaRussian Federation
Honored Doctor of Russia, MD, Professor,
Shchepkina str., 61/2, Moscow, 129110
S. I. Akberova
Russian Federation
MD, Оphthalmologist,
Kashirskoye highway, 74/1, Moscow, 115409
G. Kh. Ali-zade
Russian Federation
Research Assistant at the Ophthalmology Department of the Head and Neck Department,
Shchepkina str., 61/2, Moscow, 129110
H. F. Babayev
Azerbaijan
the chief researcher, head of the laboratory,
Sharif-zadeh str., 2, Baku, AZ1100
Yu. V. Markitantova
Russian Federation
Cand. Biol. Sciences, Chief Researcher, Head of the Regeneration Problems Laboratory,
Vavilova str., 26, Moscow, 119334
References
1. Latkany R. Dry eyes: etiology and management. Curr Opin Ophthalmol. 2008;19:287–289. DOI: 10.1097/ICU.0b013e3283023d4c
2. Fox R.I. Stern M., Michelson P. Update in Sjogren syndrome. Curr Opin Rheumatol. 2000;12:391–398. DOI: 10.1097/00002281-200009000-00007
3. Rieger G. The importance of the precorneal tear film for the quality of optical imaging. British Journal of Ophthalmology 1992;76(3):157–158. DOI: 10.1136/bjo.76.3.157
4. Egorov E.A. Features of dry eye syndrome treatment. Russian Medical Journal. Clinical Ophthalmology = Rossijskiy medicinskiy zhurnal. Klinicheskaya oftal’mologiya. 2018;3:146–149 (In Russ.).
5. Tsubota K., Fukagawa K., Fujihara T. Regulation of human leukocyte antigen expression in human conjunktival epithelium. Invest Ophthal Vis Sci. 1999;40:28–34
6. De Paiva C.S., Pfugfelder S.S. Rational for antiinflammatory therapy in dry eye syndrome. Arg Bras Oftalmol. 2008;71 (suppl.):89–95.
7. Gayton J. L. Etiology, prevalence and treatment of dry disease. Clinical ophthalmology. 2009;3:405–412. DOI: 10.2147/opth.s5555
8. Craig J.P., Nichols K.K., Akpek E.K., Caffery B., Dua H.S., Joo C.K. TFOS DEWS II definition and classification report Ocul Surf, 2017;15:276–283. DOI: 10.1016/j. jtos.2017.05.008
9. Schaumberg D.A., Sullivan D. A., Buring J.E., Dana R. Prevalence of dry eye syndrome among US women. Am J Ophthalmol 2003;136(2):318–326. DOI: 10.1016/ s0002-9394(03)00218-6
10. Schaumberg D.A., Dana R., Buring J.E., Sullivan D. A. Prevalence of dry eye disease among US men: estimates from the Physicians, Health Studies. Arch Ophthalmol 2009;127(6):363–368. DOI: 10.1001/archophthalmol.2009.103
11. Caffery B., Srinivasan S., Reaume C.J., Fischer A., Cappadocia D., Siffel C., Chan C.C. Prevalence of dry eye disease in Ontario, Canada: A population-based survey. Ocul Surf. 2019 Feb 27. PII: S1542-0124(18)30147-2. DOI: 10.1016/j. jtos.2019.02.011
12. Brzheskiy V.V. Dry eye syndrome in young people: unsolved problem of the modern time. Modern optometry = Sovremennaya optometriya 2007;2(2):38–43 (In Russ.).
13. O’ Brien P.D., Collum L.M. Dry Eye: diagnosis and current treatment strategies. JAMA. 2004;4(4):314–319. DOI: 10.1007/s11882-004-0077-2
14. Ichino M., Yokoi N., Ichino Y., Dogru M., Kawashima M., Komuro A., Sonomura Y., Kato U., Kinoshita Sh., Schaumberg D.A., Tsubota K. Prevalence of dry eye disease and nits risk factors in visual display terminal users. Am J Ophthalmol. 2013;156(4):759–766. DOI: 10.1016/j.ajo.2013.05.040
15. Stroeva O.G., Panova I.G. Regulation of mitotic activity in the cornea of rats with the protective and therapeutic effects of para-aminobenzoic acid in experiments with X-ray irradiation, Proceedings of the RAS. ser. Biological = Izvestija RAN. ser. Biologicheskaja. 1999;5:613–616 (In Russ.).
16. Sologub A.A., Panova I.G., Stroeva O.G. The influence of para-aminobenzoic acid on the level of proliferative activity in the regenerating cornea of adult rats. Ontogenesis = Ontogenez. 1994;25(6):54–59 (In Russ.).
17. Akberova S.I., Musaev-Galbinur P.I. A new interferon inducer — actipol in the treatment of herpetic keratitis. Annals of Ophthalmology = Vestnik oftal’mologii 2000;2:16–18 (In Russ.).
18. Akberova S.I., Tazulakhova E.B., Musaev Galbinur P.I., Mamedova V.M.Effect of paraaminobenzoic acid on the production of interleukin-6 in patients with herpetic keratitis. Annals of Ophthalmology = Vestnik oftal’mologii 2006;5:23–26 (In Russ.).
19. Magomedov N.M., Musaev Galbinur P.I., Akberova S.I., Stroeva O.G.. Para-aminobenzoic acid — bio-antioxidant. Ontogenesis = Ontogenez. 2000;31(4):264–265 (In Russ.).
20. Akberova S.I., Markitantova Yu.V., Ryabtseva A.A., Stroeva O.G. Hypoxia as a pathogenic factor affecting eye tissue: selective apoptotic damage to the conjunctiva and anterior corneal epithelium. Reports of the Academy of Sciences (biochemistry, biophysics and molecular biology) = Doklady AN (biohimija, biofizika i molekuljarnaja biologija). 2016;467(6):718–720 (In Russ.). DOI: 10.7868/S0869565216120240
21. Leuba G., Kraftsik R., Saini K. Quantitative Distribution of Parvalbumin, Calretinin, and Calbindin D-28k Immunoreactive Neurons in the Visual Cortex of Normal and Alzheimer Cases. Exp. Neurology. 1998;152:278–291. DOI: 10.1006/exnr.1998.6838
22. Markitantova Yu.V., Akberova S.I., Ryabtseva A.A., Stroeva O.G. The effect of para-aminobenzoic acid on apoptosis processes in the conjunctiva and cornea epithelium of adult rats in vivo after the action of hypobaric hypoxia. Proceedings of the RAS. ser. Biological = Izvestija RAN. ser. Biologicheskaja. 2018;3:257–266 (In Russ.).
23. Haskjold E., Refsum S.B., Bjerknes R. Cell renewal of the rat corneal epithelium. A method to compare corresponding corneal areas from individual animals. Acta Ophtalmologica. 1988;66:533–537. DOI: 10.1111/j.1755-3768.1988.tb04376.x
24. Blasiak J., Petrovski G, Vereb Z., Kaarniranta K. Oxidative stress, hypoxia and autophagy in the neovascular processes of age-related macular degeneration. Biomed. Res. Int. 2014;768026. DOI: 10.1155/2014/768026
25. Kalamkarov G.R., Tsapenko I.V., Zueva M.V., Ivanov A.N. An experimental model of acute retinal ischemia in rats. Experimental Biology and Medicine = Byulleten’ ehksperimental’noj biologii i mediciny. 2008;6:634–638 (In Russ.).
26. Kaur С. Hypoxia-ischemia and retinal ganglion cell damage, Clinic. Ophthalmol. 2008;2(4):879–889. DOI: 10.2147/opth.s3361
27. Peng Y. Neuroprotective effect of protease-activated receptor-2 in the hypoxiainduced apoptosis of rat RGC-5 cells, J. Mol. Neurosci. 2013;50(l):98–108. DOI: 10.1007/s12031-012-9876-4
28. Buchi E.R. Pressure induced retinal ischemia in rats: en experimental model for quantitative study. Ophtalmologica. 1991;203(3):138–147. DOI: 10.1159/000310240
Review
For citations:
Ryabtseva A.A., Akberova S.I., Ali-zade G.Kh., Babayev H.F., Markitantova Yu.V. The Protective Effect of Para-Aminobenzoic Acid in HypoxiaInduced Apoptosis of Conjunctiva and Cornea Cells in vivo. Ophthalmology in Russia. 2021;18(2):317-324. (In Russ.) https://doi.org/10.18008/1816-5095-2021-2-317-324