Retinal morphological changes in non-infectious uveitis in rabbits experimentally treated with citicoline versus non-treated rabbits

Authors

  • I. S. Gorianova SI "The Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine" https://orcid.org/0009-0004-0652-0709
  • O. V. Zborovska SI "The Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine"
  • E. V. Maltsev SI "The Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine"
  • O. E. Dorokhova SI "The Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine"

DOI:

https://doi.org/10.31288/oftalmolzh202452731

Keywords:

retina, non-infectious uveitis, neurodegeneration, neuroprotection, uveitis model, pathogenesis

Abstract

Purpose: To identify retinal morphological changes in a model of non-infectious anterior and intermediate uveitis and to assess the efficacy of experimental neuroprotective citicoline therapy in the treatment of the disease.
Material and Methods: Forty rabbits were divided in two experimental groups, the non-treatment group (18 non-treated rabbits) and treatment group (22 rabbits treated with the neuroprotector). A horse serum rabbit model was used for inducing uveitis. Histological structure of the retina was assessed on days 33 to 54 after the onset of uveitis.
Results: In the non-treatment group, there were retinal areas exhibiting marked destructive changes (sites of edema and disorganization in the inner nuclear layer, tractions between the retina and vitreous, reduced numbers of neuronal layers in the nuclear layers, and reduced numbers of ganglion cells) as well as areas of relatively well-preserved retina. At late time points after the onset of uveitis, animals treated with citicoline exhibited an almost normal retinal structure.
Conclusion: Horse serum-induced non-infectious anterior and intermediate uveitis contributed to retinal neurodegenerative changes, but uveitic animals treated with the neuroprotector for 33-54 days exhibited only minor neurodegenerative changes.

References

Tsirouki T, Dastiridou A, Symeonidis C, Tounakaki O, Brazitikou I, Kalogeropoulos C, et al. A Focus on the Epidemiology of Uveitis. Ocul Immunol Inflamm. 2018;26(1):2-16. https://doi.org/10.1080/09273948.2016.1196713

Prete M, Dammacco R, Fatone MC, Racanelli V. Autoimmune uveitis: clinical, pathogenetic, and therapeutic features. Clin Exp Med. 2016 May;16(2):125-36. https://doi.org/10.1007/s10238-015-0345-6

Burek-Michalska A, Turno-Kręcicka A. Adalimumab in the treatment of non-infectious uveitis. Adv Clin Exp Med. 2020 Oct;29(10):1231-1236. https://doi.org/10.17219/acem/125431

Horai R, Caspi RR. Microbiome and Autoimmune Uveitis. Front Immunol. 2019 Feb 19;10:232. https://doi.org/10.3389/fimmu.2019.00232

Rodriguez A, Akova YA, Pedroza-Seres M, Foster CS. Posterior segment ocular manifestations in patients with HLA-B27-associated uveitis. Ophthalmology. 1994;101(7):1267-74. https://doi.org/10.1016/S0161-6420(94)31179-1

Uy HS, Christen WG, Foster CS. HLA-B27 associated uveitis and cystoids macular edema. Ocul.Immunol.Inflam. 2001;9(3):177-83. https://doi.org/10.1076/ocii.9.3.177.3963

Klaska IP, Forrester JV. Mouse models of autoimmune uveitis. Curr Pharm Des. 2015;21(18):2453-67. https://doi.org/10.2174/1381612821666150316122928

Wildner G, Diedrichs-Möhring M. Resolution of uveitis. Semin Immunopathol. 2019 Nov;41(6):727-36. doi: 10.1007/s00281-019-00758-z. Epub 2019 Oct 7. https://doi.org/10.1007/s00281-019-00758-z

Bowers CE, Calder VL, Greenwood J, Eskandarpour M. Experimental Autoimmune Uveitis: An Intraocular Inflammatory Mouse Model. J Vis Exp. 2022 Jan 12;(179). https://doi.org/10.3791/61832

Valdes LM, Sobrin L. Uveitis Therapy: The Corticosteroid Options. Drugs. 2020 Jun;80(8):765-773. https://doi.org/10.1007/s40265-020-01314-y

Knickelbein JE, Armbrust KR, Kim M, Sen HN, Nussenblatt RB. Pharmacologic Treatment of Noninfectious Uveitis. Handb Exp Pharmacol. 2017;242:231-268. https://doi.org/10.1007/164_2016_21

Li B, Yang L, Bai F, Tong B, Liu X. Indications and effects of biological agents in the treatment of noninfectious uveitis. Immunotherapy. 2022 Aug;14(12):985-994. https://doi.org/10.2217/imt-2021-0303

Secades JJ, Gareri P. Citicoline: pharmacological and clinical review, 2022 update. Rev Neurol. 2022 Nov 30;75(s05):S1-S89. https://doi.org/10.33588/rn.75S05.2022311

Jünemann AGM, Grieb P, Rejdak R. Bedeutung von Citicolin bei der Glaukomerkrankung [The role of citicoline in glaucoma]. Ophthalmologe. 2021 May;118(5):439-448. German. https://doi.org/10.1007/s00347-021-01362-z

Park CH, Kim YS, Noh HS, Cheon EW, Yang YA, Yoo JM et al. Neuroprotective effect of citicoline against KA-induced neurotoxicity in the rat retina. Exp Eye Res. 2005;81:350-58. https://doi.org/10.1016/j.exer.2005.02.007

Park CH, Kim YS, Cheon EW, Noh HS, Cho CH, Chung IY et al. Actionof citicoline on ratret in al expression of extracellular-signal-regulated kinase (ERK1/2). Brain Res. 2006;81:203-10. https://doi.org/10.1016/j.brainres.2005.12.128

Dorokhova OE, Maltsev EV, Zborovska OV, Guanjun M. Histomorphological condition of rabbit eye with induced anterior and intermediate non-infection uveitis with normalization of the ocular surface temperature. Achievements of Clinical and Experimental Medicine. 2021;4:76-83. https://doi.org/10.11603/1811-2471.2020.v.i4.11758

Dorokhova O., Zborovska O., Meng Guanjun. Changes in temperature of the ocular surface in the projection of the ciliary body in the early stages of induced non-infectious uveitis in rabbits. J.ophthalmol [in Ukranian]. 2020;3:47-52. https://doi.org/10.31288/oftalmolzh202034752

Dorokhova O E, Zborovska OV, Guanjun Meng. Relationship of the ocular surface temperature with the clinical features of induced non-infectious anterior and intermediate uveitis in rabbits. J.ophthalmol. [in Ukranian]. 2020;6:38-43. https://doi.org/10.31288/oftalmolzh202063843

Hankey DJ, Lightman SL, Baker D. Interphotoreceptor retinoid binding protein peptide-induced uveitis in B10.RIII mice: characterization of disease parameters and immunomodulation. Exp Eye Res. 2001 Mar;72(3):341-50. https://doi.org/10.1006/exer.2000.0957

Ryan SJ. Retina. 5th Edition: Saunders; 2012. 2564 р.

Forrester JV, Borthwick GM, McMenamin PG. Ultrastructural pathology of S-antigen uveoretinitis. Invest Ophthalmol Vis Sci. 1985 Sep;26(9):1281-92.

Laksmita YA, Sidik M, Siregar NC, Nusanti S. Neuroprotective Effects of Citicoline on Methanol-Intoxicated Retina Model in Rats. J Ocul Pharmacol Ther. 2021 Nov;37(9):534-541. https://doi.org/10.1089/jop.2021.0018

Nusanti S, Sari RI, Siregar NC, Sidik M. The Effect of Citicoline on Ethambutol Optic Neuropathy: Histopathology and Immunohistochemistry Analysis of Retina Ganglion Cell Damage Level in Rat Model. J Ocul Pharmacol Ther. 2022 Oct;38(8):584-589. https://doi.org/10.1089/jop.2022.0005

Konovalova NV, Khramenko NI, Huzun OV, Kovtun AV. Reabilitatsiia khvorykh na zadnii uveit preparatom Farmakson (tsytikolin) [in Ukranian]. Terapevtyka. 2020;1(1):31-39.

Oddone F, Rossetti L, Parravano M, Sbardella D, Coletta M, Ziccardi L, Roberti G, Carnevale C, Romano D, Manni G, Parisi V. Citicoline in Ophthalmological Neurodegenerative Disease: A Comprehensive Review. Pharmaceuticals (Basel). 2021 Mar 20;14(3):281. https://doi.org/10.3390/ph14030281

García-López C, García-López V, Matamoros JA, Fernández-Albarral JA, Salobrar-García E, de Hoz R et al. The Role of Citicoline and Coenzyme Q10 in Retinal Pathology. Int J Mol Sci. 2023 Mar 7;24(6):5072. https://doi.org/10.3390/ijms24065072

Pichi F, Neri P, Hay S, Parrulli S, Zicarelli F, Invernizzi A. An en face swept source optical coherence tomography study of the vitreous in eyes with anterior uveitis. Acta Ophthalmol. 2022 May;100(3):e820-e826. https://doi.org/10.1111/aos.14965

Santina A, Bousquet E, Somisetty S, Fogel-Levin M, Tsui E, Freund KB, Sarraf D. Recurrent anterior uveitis associated with major fluctuations in choroidal thickness in patient with pachychoroid disorder. Retin Cases Brief Rep. 2024 Sep 1;18(5):562-565. https://doi.org/10.1097/ICB.0000000000001437

Peretiahina D, Shakun K, Ulianov V, Ulianova N. The Role of Retinal Plasticity in the Formation of Irreversible Retinal Deformations in Age-Related Macular Degeneration. Curr Eye Res. 2022 Jul;47(7):1043-1049. https://doi.org/10.1080/02713683.2022.2059810

Published

2024-10-29

How to Cite

1.
Gorianova IS, Zborovska OV, Maltsev EV, Dorokhova OE. Retinal morphological changes in non-infectious uveitis in rabbits experimentally treated with citicoline versus non-treated rabbits. J.ophthalmol. (Ukraine) [Internet]. 2024 Oct. 29 [cited 2024 Nov. 7];(5):27-31. Available from: https://ua.ozhurnal.com/index.php/files/article/view/199

Issue

Section

Experimental Studies