An experimental Study of the Pathogenesis of Retinopathy of Prematurity as a Promising Direction of Search for New Medicinal Approaches to its Prevention and Treatment

An experimental study was performed to reproduce the model of oxygen-induced retinopathy (OIR) in young rats. This model is promising for the study of the pathogenesis of retinopathy of prematurity (ROP) and for the search of new approaches to the prevention and treatment of the disease. It was found that the total protein content in the vitreous was increased during OIR at all observation times, with a maximum reached on the day 14. The phasal character was revealed in the changes of the level of antioxidant activity (AOA): on the day 7 AOA of rats with OIR is no different from the control, on the day 14, it becomes 6.4 times higher than the reference level, and on the day 18 (when the oxygen is no more active) it is falling but still remains higher than the norm. These findings suggest that the permeability of the blood-retinal barrier is damaged during OIR, and confirm the important role of oxidative stress in the pathogenesis of ROP, the advisability of the correction of its parameters by introducing antioxidants in the combined treatment of ROP, and the need for a differentiated approach to the times of their application Russian Ophthalmological Journal, 2016; 1: 68-72.

retinopathy of prematurity, experimental modeling, pathogenesis, blood-retinal barrier, oxidative stress, ретинопатия недоношенных, экспериментальное моделирование, патогенез, гематоретинальный барьер, окислительный стресс

1. Слепова О.С., Катаргина Л.А., Гвоздюк Н.А., Белова М.В. Влияние системной продукции ростовых факторов (VEGF и fIGF-I) на течение заболевания у детей с ретинопатией недоношенных. Российский офтальмологический журнал. 2011; 4(4): 60-6.

2. Сидоренко Е.И., Асташева И.Б., Кан И.Г. и др. Ретроспективный анализ факторов риска ретинопатии недоношенных. Российская педиатрическая офтальмология. 2010; (1): 13-6.

3. O’Donovan D.J., Fernandes C.J. Free radicals and diseases in premature infants. Antioxid Redox Signal. 2004; 6(1): 169-76.

4. Garg U., Jain A., Singla P., et al. Free radical status in retinopathy of prematurity. Ind J Clin Biochem. 2012; 27(2): 196-9.

5. Hartnett M.E., Penn J.S. Mechanisms and management of retinopathy of prematurity. N. Engl. J. Med. 2012; 367(26): 2515-26.

6. Dorfman A.L., Polosa A., Joly S., Chemtob S., Lachapelle P. Functional and structural changes resulting from strain differences in the rat model of oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2009; 50(5): 2436-50.

7. Saito Y., Geisen P., Uppal A., Hartnett M.E. Inhibition of NAD(P)H oxidase reduces apoptosis and avascular retina in an animal model of retinopathy of prematurity. Mol. Vis. 2007; 13: 840-53.

8. Grossniklaus H.E., Kang S.J., Berglin L. Animal models of choroidal and retinal neovascularization. Prog. Retin. Eye Res. 2010; 29(6): 500-19.

9. Dorfman A., Dembinska O., Chemtob S., Lachapelle P. Early manifestations of postnatal hyperoxia on the retinal structure and function of the neonatal rat. Invest. Ophthalmol. Vis. Sci. 2008; 49(1): 458-66.

10. Dorfman A.L., Cuenca N., Pinilla I., Chemtob S., Lachapelle P. Immunohistochemical evidence of synaptic retraction, cytoarchitectural remodeling, and cell death in the inner retina of the rat model of oxygen-induced retinopathy (OIR). Invest. Ophthalmol. Vis. Sci. 2011; 52(3): 1693-708.

11. Barnett J.M., Yanni S.E., Penn J.S. The Development of rat model of retinopathy of prematurity. Doc. Ophthalmol. 2010; 120(1): 3-12.

12. Zhang W., Ito Y., Berlin E., Roberts R., Berkowitz B.A. Role of hypoxia during normal retinal vessel development and in experimental retinopathy of prematurity. Invest. Ophthalmol. Vis. Sci. 2003; 44(7): 3119-23.

13. Cunningham S., McColm J.R., Wade J., et al. A novel model of retinopathy of prematurity simulating preterm oxygen variability in the rat. Invest. Ophthalmol. Vis. Sci. 2000; 41(13): 4275-80.

14. Geisen P., Peterson L.J., Martiniuk D., et al. Neutralizing antibody to VEGF reduces intravitreous neovascularization and may not interfere with ongoing intraretinal vascularization in a rat model of retinopathy of prematurity. Mol. Vis. 2008; 14: 345-57.

15. Liu K., Akula J.D., Falk C., Hansen R.M., Fulton A.B. The Retinal Vasculature and Function of the Neural Retina in a Rat Model of Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci. 2006; 47(6): 2639-47.

16. Hartnett M.E. Studies on the pathogenesis of avascular retina and neovasculatization into the vitreous in peripheral severe retinopathy of prematurity (An American Ophthalmological Society Thesis). Trans Am Ophthalmol Soc. 2010; 108: 96-119.

17. Гулидова О.В., Любицкий О.Б., Клебанов Г.И., Чеснокова Н.Б. Изменение антиокислительной активности слезной жидкости при экспериментальной ожоговой болезни глаз. Бюллетень экспериментальной биологии и медицины. 1999; 128(11): 571-4.

18. Lowry O., Rozebrough N., Farr A., Randell R. Protein mеasurement with the Folin phenol reagent. J. Bio Chem. 1951; 193: 265-75.

19. Berkowitz B.A., Roberto K.A., Penn J.S. The vitreous protein concentration is increased prior to neovascularization in experimental ROP. Curr Eye Res. 1998; 17:218-21.

20. Zhang Sarah X., Ma Jian-xing, Sima Jing, et al. Genetic Difference in Susceptibility to the Blood-Retina Barrier Breakdown in Diabetes and Oxygen-Induced Retinopathy. AJP. 2005; 166(1): 313-21.

21. Wiechmann A.F., Summers J.A. Circadian rhythms in the eye: the physiological significance of melatonin receptors in ocular tissues. Prog. Retin. Eye Res. 2008; 27(2): 137-60.