Experimental purulent corneal ulcer in rabbits as a model to study ocular dosage forms

Abstract

Aim. The aim of this work was to develop experimental model of purulent corneal ulcer in rabbits for its application in the studies of ocular dosage forms.

Methods. Rabbits body temperature was measured in three groups: (1) without corneal injury; (2) with the injury and formation of purulent ulcer, but without any therapy; (3) with the injury and formation of purulent ulcer, treated with ciprofloxacin. In parallel, swabs containing purulent discharge were taken for microbiological analysis. In the end of 10-days experiment rabbits (groups 2 and 3) were sacrificed; their corneas were extracted and analysed.

Results. One day following the injury all rabbits had a purulent discharge, moderate eyelids edema and conjunctival hyperemia. Rabbits in groups 2 and 3 had a purulent corneal ulcer developed. The mean body temperature in group 1 was 38.6±0.1 °С; in group 2 it was 40.0±0.3 °С, in group 3 it was 39.1±0.3 °С. The levels of infection in group 2 in the beginning and on 10-th day of experiments were 1.0×107 colony forming units (CFU) and 4.3×106 CFU, respectively (not significant, p >0.1). In group 3 these levels were 1.0×107 CFU and 4.6×103 CFU, respectively (significant, p <0.0001). The histological investigation of enucleated eyes with corneal ulcers revealed the presence of edema, stratification, deep epithelial defects, endothelium desquamation, and corneal infiltration by neutrophils.

Conclusion. Formation of a corneal ulcer leads to an increase in animal body temperature, which depends on timely therapy. Rectal temperature measurements in rabbits could serve as an easy parameter to follow the development of inflammation.

Keywords

purulent corneal ulcer / temperature / ciprofloxacin / staphylococcus aureus

References

[1] Vasil’ev A.E. Medicinal forms of new generation — drug delivery systems. Novaya apteka. 2002 (7): 67–70. (In Russ.)

[2] Васильев А.Е. Лекарственные формы нового поколения - системы доставки лекарственных веществ. Новая аптека. 2002 (7): 67-70.

[3] Maychuk U.F. Prevention of blindness due to corneal pathology. Vestnik oftal'mologii. 1990; (3): 58–60. (In Russ.)

[4] Майчук Ю.Ф. Профилактика слепоты как следствие патологии роговицы. Вестн. офтальмол. 1990; (3): 58-60.

[5] Bashura G.S., Bashura A.G., Yaremchuk A.A. et al. On the problem of developing new dosage forms. Farmakom. 1998; (2): 29–30, 47–50. (In Russ.)

[6] Башура Г.С., Башура А.Г., Яремчук А.А. и др. К проблеме создания новых лекарственных форм. Фармаком. 1998; (2): 29-30, 47-50.

[7] Mun E.A., Morrison P.W.J., Williams A.C., Khutoryanskiy V.V. On the barrier properties of the cornea: A microscopy study of the penetration of fluorescently labelled nanoparticles, polymers, and sodium fluorescein. Mol. Pharm. 2014; 11: 3556–3564. DOI: 10.1021/mp500332m.

[8] Mun E.A., Morrison P.W.J., Williams A.C., Khutoryanskiy V.V. On the barrier properties of the cornea: A microscopy study of the penetration of fluorescently labelled nanoparticles, polymers, and sodium fluorescein. Mol. Pharm. 2014; 11: 3556-3564. DOI: 10.1021/mp500332m.

[9] Mashkovskiy M.D. Lekarstvennye sredstva. (Medicinal preparations.) In 2 voumes. 16-th edition, revised, amended, supplemented. Moscow: Novaya Volna. 2001; 2: 608. (In Russ.)

[10] Машковский М.Д. Лекарственные средства. В 2 т. 16-е изд., перераб., испр. и доп. М.: Новая Волна. 2001; 2: 608 с.

[11] Arzamastsev A.P. The main directions for development and evaluation of the quality of medicines. Voprosy biologii, meditsiny i farmatsevticheskoy khimii. 2001; (4): 3–5. (In Russ.)

[12] Арзамасцев А.П. Основные направления создания и оценки качества лекарственных средств. Вопр. биол., мед. и фарм. химии. 2001; (4): 3-5.

[13] Wilson C.G., Zhu Y.P., Kumala P. et al. Ophthalmic drug delivery. In: Drug delivery and targeting for pharmacists and pharmaceutical scientists. A.M. Hillery, A.W. Lloyd, J. Swarbrick (Eds). CRS Press, FL, USA, 2001, 329–353.

[14] Wilson C.G., Zhu Y.P., Kumala P. et al. Ophthalmic drug delivery. In: Drug delivery and targeting for pharmacists and pharmaceutical scientists. A.M. Hillery, A.W. Lloyd, J. Swarbrick (Eds). CRS Press, FL, USA, 2001, 329-353.

[15] Cejkova J., Cejka C., Trosan P. et al. Treatment of alkali-injured cornea by cyclosporine A-loaded electrospun nanofibers — An alternative mode of therapy. Exp. Eye Res. 2016; 147: 128–137. DOI: 10.1016/j.exer.2016.04.016.

[16] Cejkova J., Cejka C., Trosan P. et al. Treatment of alkali-injured cornea by cyclosporine A-loaded electrospun nanofibers - An alternative mode of therapy. Exp. Eye Res. 2016; 147: 128-137. DOI: 10.1016/j.exer.2016.04.016.

[17] Baum J. Treatment of bacterial ulcers of the cornea in the rabbit: A comparison of administration by eye drops and subconjuctival injections. Rev. Trans Am. Ophthalm. Soc. 1982; 80: 369–390. PMID: 6763800.

[18] Baum J. Treatment of bacterial ulcers of the cornea in the rabbit: A comparison of administration by eye drops and subconjuctival injections. Rev. Trans Am. Ophthalm. Soc. 1982; 80: 369-390. PMID: 6763800.

[19] Kolesnikov A.V., Schul’kin A.V., Barenina O.I., Konoplyova V.I. Local and systemic antioxidant status in experimental corneal purulent ulcer. Kazanskiy meditsinskiy zhurnal. 2013; (4): 571–575. (In Russ.)

[20] Колесников А.В., Щулькин А.В., Баренина О.И., Коноплёва В.И. Локальный и системный антиоксидантный статус при экспериментальной гнойной язве роговицы. Казанский мед. ж. 2013; (4): 571-575.

[21] Kolesnikov A.V. Analysis of the impact of acetylcysteine on free radical status the antioxidant system of the cornea with experimental purulent ulcer. Ufimskiy nauchno-prakticheskiy zhurnal. 2017; (1): 71–73. (In Russ.)

[22] Колесников А.В. Анализ влияния ацетилцистеина на свободнорадикальный статус и состояние антиоксидантной системы роговицы при стафилококковой гнойной язве роговицы в эксперименте. Уфимский науч.-практ. ж. 2017; (1): 71-73.

[23] European Convention for the Protection of Vertebrate Animals used for. Experimental and Other Scientific Purposes. (Strasbourg, 18.III.1986). http://base.garant.ru/4090914/ (access date: 11.12.2017). (In Russ.)

[24] Европейская конвенция о защите позвоночных животных, используемых для экспериментов или в иных научных целях (Страсбург, 18 марта 1986 г.). http://base.garant.ru/4090914/ (дата обращения: 11.12.2017).

[25] Pericin С., Grieve A.P. Seasonal variation of temperatures in rabbits. Laboratory Animals. 1984; 18: 230–236. DOI: 10.1258/002367784780958132.

[26] Pericin С., Grieve A.P. Seasonal variation of temperatures in rabbits. Laboratory Animals. 1984; 18: 230-236. DOI: 10.1258/002367784780958132.

RIGHTS & PERMISSIONS

Ozhmukhametova E.K., Mussin M.N., Bayachmetov A., Adambosynov B., Khutoryanskiy V.V.