Tear lactoferrin and ceruloplasmin levels in patients with traumatic and recurrent corneal erosions

Authors

  • Iryna Gavrylyak Bogomolets National Medical University
  • Dmytro Zhaboiedov Bogomolets National Medical University
  • Natalya Greben Bogomolets National Medical University
  • Artem Tykhomyrov O. V. Palladin Institute of Biochemistry, the National Academy of Sciences of Ukraine

DOI:

https://doi.org/10.31288/oftalmolzh20241814

Keywords:

corneal trauma, lactoferrin, ceruloplasmin, recurrent corneal erosion

Abstract

Background: Studies on the mechanisms of corneal wound healing are still important. Apart from the integrity of the corneal epithelium, tear fluid is important for maintaining homeostasis of the ocular surface; it is composed of a variety of proteins, lipids and metabolites. Studies on changes in concentrations of biochemical tear components are important for the diagnosis and treatment of corneal injuries.

Purpose: To assess changes in tear lactoferrin (Lf) and ceruloplasmin (Cp) levels over the course of comprehensive treatment for patients with traumatic corneal erosions (TCE) and recurrent corneal erosions (RCE).

Material and Methods: The study sample included 62 patients (19 to 65 years of age; mean age plus or minus standard deviation, 43.5 ± 2.4 years). Group 1 included 44 patients with TCE, and group 2, 18 patients with recurrent RCE. Each patient group was divided into two subgroups on the basis of the treatment method. Subgroup 1 was administered eye broad-spectrum antibiotic (AB) eye drops and dexpantenol over a course of treatment. Subgroup 2 received AB eye drops and dexpantenol plus adjunct lactoferrin (Lf)-containing eye drops. An eye examination included visual acuity, biomicroscopy and fluorescein test. Monospecific antibodies were used to determine tear Lf and Cp levels. Tears from healthy volunteers were used as controls.

Results: At baseline, the tear Lf level in patients with TCR was lower than in controls (3.94 ± 0.45 arbitrary units (a.u.) versus 10.3 ± 0.4 a.u., respectively; p < 0.05), resulting in reduced ocular surface protection. In subgroup 1 of the TCE group, after treatment with an AB plus dexpantenol only, the tear Lf level increased to 6.38 ± 0.55 a.u. (p < 0.05), and the mean period of treatment was 7.6 ± 0.43 days (p ≥ 0.1). In subgroup 2 of the TCE group, after treatment with an AB plus dexpantenol plus Lf-containing eye drops, the tear Lf level was 12.23 ± 0.6 a.u. (p < 0.05) and the mean period of treatment was 6.0 ± 0.23 days. The presence of Cp in the tear fluid prior to treatment for TCE or RCE indicated activation of acute inflammation; at baseline, the tear Cp level in patients with TCE was 2.37 ± 0.25 a.u. compared to controls (p < 0.05), and in those with RCE, 1.78 ± 0.2 a.u. On completion of treatment with Lf-containing eye drops, the tear Lf level increased and the tear Cp level decreased to the levels in controls, and there was a negative correlation between the tear Lf level and the tear Cp level (r = -0.491, p < 0.001).

Conclusion: The results confirmed the feasibility of utlizing Lf-containing eye drops as an adjunct in the treatment of TCE and RCE. This approach contributed to the restoration of ocular surface homeostasis, thus promoting corneal epithelialization and enabling a reduction in treatment duration.

Author Biography

Artem Tykhomyrov , O. V. Palladin Institute of Biochemistry, the National Academy of Sciences of Ukraine

Відділ хімії та біохімії ферментів

References

Barrientez B, Nicholas SE, Whelchel A, Sharif R, Hjortdal J, Karamichos D. Corneal injury: Clinical and molecular aspects. Exp Eye Res. 2019 Sep;186:107709. https://doi.org/10.1016/j.exer.2019.107709

Willmann D, Fu L, Melanson SW. Corneal Injury. 2023 Jul 17. In: Stat Pearls [Internet]. Treasure Island (FL): Stat Pearls Publishing; 2023. PMID: 29083785.

Nuzzi A, PozzoGiuffrida F, Luccarelli S, Nucci P. Corneal Epithelial Regeneration: Old and New Perspectives. Int J Mol Sci. 2022 Oct 28;23(21):13114. https://doi.org/10.3390/ijms232113114

Wilson SE, Torricelli AAM, Marino GK. Corneal epithelial basement membrane: Structure, function, and regeneration. Exp Eye Res. 2020 May;194:108002. https://doi.org/10.1016/j.exer.2020.108002

Miller DD, Hasan SA, Simmons NL, Stewart MW. Recurrent corneal erosion: a comprehensive review. Clin Ophthalmol. 2019 Feb 11;13:325-335. https://doi.org/10.2147/OPTH.S157430

Jan RL, Tai MC, Ho CH, Chu CC, Wang JJ, Tseng SH, et al. Risk of recurrent corneal erosion in patients with diabetes mellitus in Taiwan: a population-based cohort study. BMJ Open. 2020;10:e035933. https://doi.org/10.1136/bmjopen-2019-035933

Paley GL, Wagoner MD, Afshari NA, Pineda R, Huang AJW, Kenyon KR. Corneal Wound Healing, Recurrent Corneal Erosions, and Persistent Epithelial Defects. In: Albert DM, Miller JW, Azar, DT, Young LH. (eds). Albert and Jakobiec's Principles and Practice of Ophthalmology. Springer, 2022. Cham. https://doi.org/10.1007/978-3-030-42634-7_212

Zhan X, Li J, Guo Y, Golubnitschaja O. Mass spectrometry analysis of human tear fluid biomarkers specific for ocular and systemic diseases in the context of 3P medicine. EPMA J. 2021 Dec 3;12(4):449-75. https://doi.org/10.1007/s13167-021-00265-y

Liu Z, Wang M, Zhang C, Zhou S, Ji G. Molecular Functions of Ceruloplasmin in Metabolic Disease Pathology. Diabetes Metab Syndr Obes. 2022 Mar 3;15:695-711. https://doi.org/10.2147/DMSO.S346648

Wang B, Timilsena YP, Blanch E, Adhikari B. Lactoferrin: Structure, function, denaturation and digestion. Crit Rev Food Sci Nutr. 2019;59(4):580-596. https://doi.org/10.1080/10408398.2017.1381583

Drozhzhyna GI, Riazanova LIu, Khramenko NI, Velychko LM. Lactoferrin concentration in tears of patients with chronic conjunctivitis and effect of Lacto eyedrops in the multicomponent treatment for this disorder. J of Ophthalnology (Ukraine). 2023;1:39-46. https://doi.org/10.31288/oftalmolzh202313945

Vagge A, Senni C, Bernabei F, Pellegrini M, Scorcia V, Traverso CE, Giannaccare G. Therapeutic Effects of Lactoferrin in Ocular Diseases: From Dry Eye Disease to Infections. Int J MolSci. 2020 Sep 12;21(18):6668. https://doi.org/10.3390/ijms21186668

Orzheshkovskyi VV, Trishchynska MA. Ceruloplasmin: its role in the physiological and pathological processes. Neurophysiology. 2019; 51:141-149. https://doi.org/10.1007/s11062-019-09805-9

Bonaccorsidi Patti MC, Cutone A, Polticelli F, Rosa L, Lepanto MS, Valenti P, Musci G. The ferroportin-ceruloplasmin system and the mammalian iron homeostasis machine: regulatory pathways and the role of lactoferrin. Biometals. 2018 Jun;31(3):399-414. https://doi.org/10.1007/s10534-018-0087-5

Tykhomyrov A, Yusova O, Kapustianenko L, Bilous V, Drobotko T, Gavryliak I, et al. Production of anti-lactoferrin antibodies and their application in the analysis of the tear fluid. Biotech Acta. 2022; 15(5):31-40. https://doi.org/10.15407/biotech15.05.031

Zeitler AF, Gerrer KH, Haas R, Jiménez-Soto LF. Optimized semi-quantitative blot analysis in infection assays using the Stain-Free technology. J Microbiol Methods. 2016 Jul;126:38-41. https://doi.org/10.1016/j.mimet.2016.04.016

Wilson SE. Corneal wound healing. Exp Eye Res. 2020 Aug;197:108089. https://doi.org/10.1016/j.exer.2020.108089

Thompson MW. Regulation of zinc-dependent enzymes by metal carrier proteins. Biometals. 2022 Apr;35(2):187-213. https://doi.org/10.1007/s10534-022-00373-w

Kell DB, Heyden EL, Pretorius E. The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria. Front Immunol. 2020 May 28;11:1221. https://doi.org/10.3389/fimmu.2020.01221

Drozhzhyna GI, Velyksar TA. [Lactoferrin: an invisible eye protector]. Oftalmologiia. Ukrainskyi zhurnal. 2021;1(12):73-85. Ukrainian. https://doi.org/10.30702/Ophthalmology31032021-12.1.73-84/048.8

Ohradanova-Repic A, Praženicová R, Gebetsberger L, Moskalets T, Skrabana R, Cehlar O, et al. Time to Kill and Time to Heal: The Multifaceted Role of Lactoferrin and Lactoferricin Host Defense. Pharmaceutics. 2023 Mar 24;15(4):1056. https://doi.org/10.3390/pharmaceutics15041056

Regueiro U, López-López M, Varela-Fernández R, Sobrino T, Diez-Feijoo E, Lema I. Immunomodulatory Effect of Human Lactoferrin on Toll-like Receptors 2 Expression as Therapeutic Approach for Keratoconus. Int J MolSci. 2022 Oct15;23(20):12350. https://doi.org/10.3390/ijms232012350

Higuchi A, Inoue H, Kaneko, Y. et al. Selenium-binding lactoferrin is taken into corneal epithelial cells by a receptor and prevents corneal damage in dry eye model animals. Sci Rep. 2016; 6: 36903. https://doi.org/10.1038/srep36903

Burcel M, Constantin M, Ionita G, Gabriela, Covilitir V. Levels of lactoferrin, lysozyme and albumin in the tear film of keratoconus patients and their correlations with important parameters of the disease. Revista Română de Medicină de Laborator. 2020; 28:2. https://doi.org/10.2478/rrlm-2020-0018

Published

2024-02-29

How to Cite

1.
Gavrylyak I, Zhaboiedov D, Greben N, Tykhomyrov A. Tear lactoferrin and ceruloplasmin levels in patients with traumatic and recurrent corneal erosions. J.ophthalmol. (Ukraine) [Internet]. 2024 Feb. 29 [cited 2024 Apr. 29];(1):8-14. Available from: https://ua.ozhurnal.com/index.php/files/article/view/76

Issue

Section

Clinical Ophthalmology