Toll-like receptors as diagnostic targets in pellucid marginal degeneration

Uxía Regueiro; María Pérez-Mato; Pablo Hervella; Francisco Campos; Tomás Sobrino; Isabel Lema

doi:10.1016/j.exer.2020.108211

Toll-like receptors as diagnostic targets in pellucid marginal degeneration

Exp Eye Res. 2020 Nov:200:108211. doi: 10.1016/j.exer.2020.108211. Epub 2020 Sep 2.

Authors

Uxía Regueiro¹, María Pérez-Mato², Pablo Hervella², Francisco Campos², Tomás Sobrino³, Isabel Lema⁴

Affiliations

¹ Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain; Facultade de Óptica e Optometría, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain.
² Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
³ Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. Electronic address: tomas.sobrino.moreiras@sergas.es.
⁴ Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain; Facultade de Óptica e Optometría, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain; Instituto Galego de Oftalmoloxía (INGO), Hospital Provincial de Conxo, Santiago de Compostela, Spain. Electronic address: mariaisabel.lema@usc.es.

PMID: 32890481
DOI: 10.1016/j.exer.2020.108211

Abstract

The main purpose of this study is to evaluate the diagnostic role of Toll-like receptors 2 (TLR2) and 4 (TLR4) expression in corneal and conjunctival epithelial cells of eyes with pellucid marginal degeneration (PMD) compared to keratoconus patients (KC) and control subjects. A prospective case-control study in 29 PMD eyes, 109 KC eyes and 72 healthy eyes was done. All participants were subjected to a clinical, topographic, aberrometric and tomographic exam with extraction of corneal and conjunctival epithelial cells through scraping. The TLR2 and TLR4 expression was measured with flow cytometry. Receiver operating characteristic (ROC) curve analysis was used to determine the most appropriate cutoff point for predicting the risk of PMD and KC. Correlations between TLR2/TLR4 expression and the severity of PMD/KC were evaluated. A TLRs follow-up review was made 19 ± 4 months after to the first review. As result, mean expression of TLR2 and TLR4 in both corneal and conjunctival epithelial cells was significantly higher in eyes with corneal ectasia (PMD and KC) than in control eyes (all p < 0.05). Conjunctival TLR4 expression showed the highest capacity to diagnose the existence of PMD (odd ratio 42.84; 95% confidence interval:6.20-296.20; p < 0.0001) after adjusting by eye rubbing and steeper corneal meridian. Moreover, we found an association between the TLR2/TLR4 overexpression with the severity of the PMD and KC measured by corneal topographic, aberrometric and tomographic quantitative parameters (all p < 0.05). Differences on TLR2/TLR4 expression between study groups were maintained during the follow-up period. In conclusion, the TLR2/TLR4 overexpression in corneal and conjunctival epithelial cells of PMD and KC patients compared to healthy control subjects have demonstrated their role as diagnostic target in both corneal ectatic disorders.

Keywords: Corneal ectasia; Innate immunity; Keratoconus; Pellucid marginal degeneration; Toll-like receptors 2; Toll-like receptors 4.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Child
Conjunctiva / metabolism
Conjunctiva / physiology*
Cornea / metabolism
Cornea / pathology*
Corneal Topography
Female
Gene Expression Regulation*
Humans
Keratoconus / diagnosis*
Keratoconus / genetics
Keratoconus / metabolism
Male
Middle Aged
Prospective Studies
RNA / genetics*
ROC Curve
Toll-Like Receptors / biosynthesis
Toll-Like Receptors / genetics
Young Adult

Substances

Toll-Like Receptors
RNA