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Graefe's Archive for Clinical and Experimental Ophthalmology
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 2/2021

01-02-2021 | Cornea

Corneal and conjunctival alteration of innate immune expression in first-degree relatives of keratoconus patients

Authors: Uxía Regueiro, Maite López-López, Pablo Hervella, Tomás Sobrino, Isabel Lema

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 2/2021

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Abstract

Purpose

The innate immune toll-like receptors 2 (TLR2) and 4 (TLR4) may play a key role in the physiopathology of keratoconus (KC). Therefore, the aim of this study was to compare TLR2/TLR4 expression in corneal and conjunctival epithelial cells between healthy first-degree relatives of patients with KC and healthy controls as well as KC patients.

Methods

Case-control study in 72 healthy eyes of 36 control subjects, 53 eyes of 27 first-degree relatives, and 109 eyes with KC (60 patients). All participants were subjected to a clinical, topographic, aberrometric, and tomographic examination with extraction of corneal and conjunctival epithelial cells through scraping. TLR2/TLR4 expression was measured by flow cytometry, and was compared among controls, first-degree relatives, and KC patients. The relationship between TLR expression and epidemiological-clinical variables or topographic-aberrometric-tomographic parameters was also analyzed.

Results

Mean TLR2/TLR4 expression showed a significant gradual increase among groups: controls < first-degree relatives < KC patients. Mean expression of TLR2 in corneal epithelial cells and both TLR2/TLR4 in conjunctival epithelial cells were significantly higher in relatives than in controls (p = 0.026, p < 0.001, and p = 0.031, respectively). Sex, age, allergic disease, eye itching, rubbing, and topographic-aberrometric-tomographic parameters were not associated to TLR2/TLR4 expression in relatives. TLR2 conjunctival expression was independently associated to relatives (OR 1.001; CI 95% 1.000–1.002, p = 0.043) after adjustment by sex, age, and rubbing.

Conclusion

TLR2 and TLR4 are overexpressed in corneal and conjunctival epithelial cells of KC relatives compared with controls. Both biomarkers may monitor early ocular changes in first-degree relatives who not show any abnormal clinical-topographic-aberrometric-tomographic parameters.
Literature
1.
Belin MW, Asota IM, Ambrosio R, Khachikian SS (2011) What’s in a name: keratoconus, pellucid marginal degeneration, and related thinning disorders. Am J Ophthalmol 152:157–162PubMedCrossRef
2.
3.
Godefrooij DA, Mangen MJJ, Chan E et al (2017) Cost-effectiveness analysis of corneal collagen crosslinking for progressive keratoconus. Ophthalmology 124:1485–1495PubMedCrossRef
4.
Chan E, Baird PN, Vogrin S, Sundararajan V, Daniell MD, Sahebjada S (2020) Economic impact of keratoconus using a health expenditure questionnaire: a patient perspective. Clin Exp Ophthalmol 48(3):287–300PubMedCrossRef
5.
Mas Tur V, MacGregor C, Jayaswal R, O’Brart D, Maycock N (2017) A review of keratoconus: diagnosis, pathophysiology, and genetics. Surv Ophthalmol 62:770–783PubMedCrossRef
6.
Kolozsvári BL, Petrovski G, Gogolák P et al (2014) Association between mediators in the tear fluid and the severity of keratoconus. Ophthalmic Res 51(1):46–51PubMedCrossRef
7.
Lema I, Duran J (2005) Inflammatory molecules in the tears of patients with keratoconus. Ophthalmology 112(4):654–659PubMedCrossRef
8.
Wisse RP, Kuiper JJ, Gans R, Imhof S, Radstake TR, Van der Lelij A (2015) Cytokine expression in keratoconus and its corneal microenvironment: a systematic review. Ocul Surf 13(4):272–283PubMedCrossRef
9.
Malfeito M, Regueiro U, Pérez-Mato M, Campos F, Sobrino T, Lema I (2019) Innate immunity biomarkers for early detection of keratoconus. Ocul Immunol Inflamm 27:942–948PubMedCrossRef
10.
Sobrino T, Regueiro U, Malfeito M, Vieites-Prado A, Pérez-Mato M, Campos F, Lema I (2017) Higher expression of toll-like receptors 2 and 4 in blood cells of keratoconus patients. Sci Rep 7:12975PubMedPubMedCentralCrossRef
11.
12.
13.
14.
Kaya V, Utine CA, Altunsoy M, Oral D, Yilmaz OF (2008) Evaluation of corneal topography with Orbscan II in first-degree relatives of patients with keratoconus. Cornea 27:531–534PubMedCrossRef
15.
Zadnik K, Barr JT, Edrington TB et al (1998) Baseline findings in the collaborative longitudinal evaluation of keratoconus (CLEK) study. Invest Ophthalmol Vis Sci 39:2537–2546PubMed
16.
Awwad ST, Yehia M, Mehanna C-J, Fattah MA, Saad A, Hatoum A, Al-Haddad C (2019) Tomographic and refractive characteristics of pediatric first-degree relatives of keratoconus patients. Am J Ophthalmol 207:71–76PubMedCrossRef
17.
Levy D, Hutchings H, Rouland JF et al (2004) Videokeratographic anomalies in familial keratoconus. Ophthalmology 111:867–874PubMedCrossRef
18.
19.
Fam H-B, Lim K-L (2006) Corneal elevation indices in normal and keratoconic eyes. J Cataract Refract Surg 32:1281–1287PubMedCrossRef
20.
Krachmer JH, Feder RS, Belin MW (1984) Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol 28:293–322PubMedCrossRef
21.
Alió JL, Shabayek MH (2006) Corneal higher order aberrations: a method to grade keratoconus. J Refract Surg 22:539–545PubMedCrossRef
22.
Zhang Z, Schluesener HJ (2006) Mammalian toll-like receptors: from endogenous ligands to tissue regeneration. Cell Mol Life Sci 63:2901–2907PubMedCrossRef
23.
Ionescu IC, Corbu CG, Tanase C et al (2018) Overexpression of tear inflammatory cytokines as additional finding in keratoconus patients and their first degree family members. Mediat Inflamm 2018:4285268CrossRef
24.
Akdis M, Burgler S, Crameri R et al (2011) Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases. J Allergy Clin Immunol 127:701–721PubMedCrossRef
25.
Sorkhabi R, Ghorbanihaghjo A, Taheri N, Ahoor MH (2015) Tear film inflammatory mediators in patients with keratoconus. Int Ophthalmol 35:467–472PubMedCrossRef
26.
Balasubramanian SA, Mohan S, Pye DC, Willcox MD (2012) Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus. Acta Ophthalmol 90:303–309CrossRef
27.
Kara N, Altinkaynak H, Baz O, Goker Y (2013) Biomechanical evaluation of cornea in topographically normal relatives of patients with keratoconus. Cornea 32:262–266PubMedCrossRef
28.
Ionescu IC, Corbu CG, Nicula C et al (2018) The importance of corneal biomechanics in assessing first degree family members of keratoconus patients. Rom J Ophthalmol 61:149–154CrossRef
29.
Dogru M, Karakaya H, Özçetin H et al (2003) Tear function and ocular surface changes in keratoconus. Ophthalmology 110:1110–1118PubMedCrossRef
30.
Ziangirova GG, Antonova OV (2002) The causes of necrobiosis and apoptosis of corneal epithelial cells during primary acquired keratoconus. Izv Akad Nauk Ser Biol 5:517–521
31.
El-Khoury S, Abdelmassih Y, Hamade A et al (2016) Pediatric keratoconus in a tertiary referral center: incidence, presentation, risk factors, and treatment. J Refract Surg 32:534–541PubMedCrossRef
Metadata
Title
Corneal and conjunctival alteration of innate immune expression in first-degree relatives of keratoconus patients
Authors
Uxía Regueiro
Maite López-López
Pablo Hervella
Tomás Sobrino
Isabel Lema
Publication date
01-02-2021
Publisher
Springer Berlin Heidelberg
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 2/2021
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-020-04929-9

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