Corneal and conjunctival alteration of innate immune expression in first-degree relatives of keratoconus patients
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CORNEA
Corneal and conjunctival alteration of innate immune expression in first-degree relatives of keratoconus patients Uxía Regueiro 1,2
&
Maite López-López 2 & Pablo Hervella 1
&
Tomás Sobrino 1
&
Isabel Lema 1,2,3
Received: 10 July 2020 / Revised: 1 September 2020 / Accepted: 10 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 clinicaltopographic-aberrometric-tomographic parameters.
Keywords Corneal and conjunctival epithelial cells . Innate immunity . Keratoconus . Relatives . Toll-like receptor 2 and 4 Abbreviations AFU CI
Arbitrary fluorescence units Confidence interval
* Tomás Sobrino [email protected] * Isabel Lema [email protected] 1
Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
2
Facultade de Óptica e Optometría, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
3
Instituto Galego de Oftalmoloxía (INGO), Hospital Provincial de Conxo, Santiago de Compostela, Spain
dK D DCP HSP I-S asymmetry IL-1β IL-4 KC maxDP μm MTP NF-κB OR % PE
Corneal astigmatism Diopters Dioptric central power Heat shock proteins Inferior-superi
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