Inflammatory profile of keratoconic corneal epithelium (original) (raw)
Related papers
Increased lacrimal inflammatory mediators in patients with keratoconus
PubMed, 2021
Purpose: This study aimed to characterize the tear film immunologic profile in keratoconus (KC) patients compared with healthy individuals (control group) and to investigate the correlation between the tear film immunologic profile and atopy, disease severity, and disease status over time. Methods: The study involved 30 KC patients and 18 healthy individuals. Tear collection was obtained using microcapillary tubes. Tear film levels of fractalkine, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-21, IL-23, interferon-inducible T-cell alpha chemoattractant (ITAC), macrophage inflammatory protein-1 alpha (MIP-1α), MIP-1β, MIP-3α, and tumor necrosis factor (TNF)-α were detected. Keratometric measurements and topographic patterns were used to diagnose and define disease progression. Tear immunologic profiles were compared, emphasizing the presence or absence of ocular allergy. Correlations between the cytokine profile, disease severity, and disease status were also analyzed longitudinally in the KC patients. Results: Lacrimal cytokine concentrations were higher in the KC patients than they were in the controls in 14 of 21 cytokines analyzed. IL-6 was the most relevant cytokine found in KC patients, especially when associated with ocular allergy. There was no correlation between KC progression and the level of inflammatory cytokines when analyzed longitudinally. KC severity correlated with IL-6 concentration, where the more severe KC presented a higher IL-6 concentration in tears. Conclusions: Inflammatory activity seems to be involved in the pathogenesis of KC. Out of 21 cytokines, 14 were more concentrated in the tears of KC patients than healthy subjects. IL-6 was significantly higher in KC patients' tears and was related to disease severity. Disease progression did not correlate with cytokine levels when analyzed longitudinally.
Subclinical keratoconus and inflammatory molecules from tears
British Journal of Ophthalmology, 2009
Background/Aims: Tissue degradation in corneal thinning disorders, such as keratoconus (KC), involves the expression of inflammatory mediators. The purpose of this study was to determine the levels of proinflammatory cytokines and matrix metalloproteinase 9 (MMP-9) in tears from both eyes of unilateral keratoconus (KC) patients.
Mediators of inflammation, 2018
Keratoconus is a progressive corneal ectasia that may lead to severe visual impairment due to the irregular astigmatism caused by corneal thinning. In addition to its association with atopy, eye rubbing, or genetic component, late reports suggest the involvement of inflammation in the pathogenesis of the disease. Our aim was to determine the concentration of IL-4, IL-6, IL-10, RANTES, IFN gamma, and TNF alpha in the tear film of patients with keratoconus and their first degree family members. We analyzed forty-eight participants in an observational cross-sectional study. The diagnosis of keratoconus had to be confirmed in addition to a minimum of 47 D corneal refractive power by corneal topography readings provided by a Placido-based topography system and analysis of the pattern: irregular astigmatism with an asymmetric "bow-tie." As for the other groups, the most important diagnosis criteria were a normal topographic pattern with a regular astigmatism. 17 keratoconus pati...
Subnormal Cytokine Profile in the Tear Fluid of Keratoconus Patients
PLoS ONE, 2011
Keratoconus, historically viewed as a non-inflammatory disease, is an ectatic corneal disorder associated with progressive thinning of the corneal stroma. Recently, a few inflammatory mediators have been reported to be elevated in the tear fluid of keratoconus patients. Consequently, we investigated a wide range of inflammation regulating cytokines in the tears and sera of keratoconus and control subjects. Interleukin (IL)-1b, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17, interferon (IFN)-c, chemokine C-C motif ligand 5 (CCL5) and tumor necrosis factor (TNF)-a were tested in tear samples and sera of keratoconus and control individuals by multiplex immuno-bead assays. Selected cytokines were further tested by standard ELISA on pooled tear samples. All cytokines in the sera were generally low, with no significant changes between keratoconus and control subjects. However, in tear fluids, clear differences were detected between the two groups. These differences include increased IL-6, and decreased IL-12, TNF-a, IFN-c, IL-4, IL-13 and CCL5 in keratoconus compared to control tear fluids. The decreases in IL-12, TNF-a and CCL5 were statistically significant, while the IL-13 decrease was statistically significant in the severe keratoconus group only. IL-17 could not be detected by multiplex immuno-bead assay, but showed an increase in keratoconus by conventional ELISA on a limited number of pooled tear samples. Our findings confirm increased IL-6, but dispute earlier reports of increased TNF-a, and suggest a cytokine imbalance in keratoconus disrupting corneal homeostasis. Moreover, an increase in IL-17 suggests tissue degenerative processes at work, contributing to the thinning and weakening of the corneal connective tissue in keratoconus.
Keratoconus patients exhibit a distinct ocular surface immune cell and inflammatory profile
Scientific Reports
Inflammatory factors have been considered to contribute to keratoconus (KC) pathogenesis. This study aims to determine the immune cells subsets and soluble inflammatory factor profile on the ocular surface of KC patients. 32 KC subjects (51 eyes) across different grades of severity and 15 healthy controls (23 eyes) were included in the study. Keratometry and pachymetry measurements were recorded. Ocular surface immune cells (collected by ocular surface wash) immunophenotyped using flow cytometry include leukocytes, neutrophils, macrophages, natural killer (NK) cells, pan-T cells, gamma delta T (γδT) cells and NKT cells. Tear fluid collected using Schirmer’s strip was used to measure 50 soluble factors by multiplex ELISA. Proportions of activated neutrophils, NK cells and γδT cells were significantly increased in KC patients. Significantly higher levels of tear fluid IL-1β, IL-6, LIF, IL-17A, TNFα, IFNα/β/γ, EPO, TGFβ1, PDGF-BB, sVCAM, sL-selectin, granzyme-B, perforin, MMP2, sFasL a...
Keratoconus: an inflammatory disorder?
Eye, 2015
Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.
Investigative Ophthalmology & Visual Science, 2011
To study the density and morphologic characteristics of epithelial dendritic cells, as correlated to subbasal corneal nerve alterations in acute infectious keratitis (IK) by in vivo confocal microscopy (IVCM). METHODS. IVCM of the central cornea was performed prospectively in 53 eyes with acute bacterial (n ϭ 23), fungal (n ϭ 13), and Acanthamoeba (n ϭ 17) keratitis, and in 20 normal eyes, by using laser in vivo confocal microscopy. Density and morphology of dendritic-shaped cells (DCs) of the central cornea, corneal nerve density, nerve numbers, branching, and tortuosity were assessed and correlated. It should be noted that due to the "in vivo" nature of the study, the exact identity of these DCs cannot be specified, as they could be monocytes or tissue macrophages, but most likely dendritic cells. RESULTS. IVCM revealed the presence of central corneal DCs in all patients and controls. The mean DC density was significantly higher in patients with bacterial (441.1 Ϯ 320.5 cells/ mm 2 ; P Ͻ 0.0001), fungal (608.9 Ϯ 812.5 cells/mm 2 ; P Ͻ 0.0001), and Acanthamoeba keratitis (1000.2 Ϯ 1090.3 cells/ mm 2 ; P Ͻ 0.0001) compared with controls (49.3 Ϯ 39.6 cells/ mm 2 ). DCs had an increased size and dendrites in patients with IK. Corneal nerves were significantly reduced in eyes with IK compared with controls across all subgroups, including nerve density (674.2 Ϯ 976.1 vs. 3913.9 Ϯ 507.4 m/frame), total nerve numbers (2.7 Ϯ 3.9 vs. 20.2 Ϯ 3.3), main trunks (1.5 Ϯ 2.2 vs. 6.9 Ϯ 1.1), and branching (1.2 Ϯ 2.0 vs. 13.5 Ϯ 3.1; P Ͻ 0.0001). A strong association between the diminishment of corneal nerves and the increase of DC density was observed (r ϭ Ϫ0.44; P Ͻ 0.0005). CONCLUSIONS. IVCM reveals an increased density and morphologic changes of central epithelial DCs in infectious keratitis. There is a strong and significant correlation between the increase in DC numbers and the decreased subbasal corneal nerves, suggesting a potential interaction between the immune and nervous system in the cornea. (Invest Ophthalmol Vis Sci.
Tear Cytokine Levels in Vernal Keratoconjunctivitis
Cornea, 2013
The aims of this study were to evaluate the efficacy of topical 0.05% cyclosporine A on clinical signs and symptoms of vernal keratoconjunctivitis (VKC) and to examine its effect on tear cytokine levels. Methods: Twenty-one patients with active VKC and 15 healthy volunteers were included. Patients were treated with topical 0.05% cyclosporine A. Symptoms and signs were scored on the day of enrollment and at the end of month 1 and month 3. Tear and serum samples were collected before and on the third month of treatment. Interleukin (IL)-2, soluble IL-2 receptor (sIL-2R), IL-3, IL-4, IL-5, IL-6, IL-9, IL-13, IL-17, eotaxin, tumor necrosis factor alpha (TNF-a), and interferon gamma (IFN-g) in cell-free tear and serum supernatants were measured by multiplex bead analysis. Results: At the end of month 1 and month 3 with topical 0.05% cyclosporine A treatment, statistically a significant decrease was observed in sign and symptom scores of the patients (P , 0.0001). Tear IL-2, sIL-2R, IL-9, IL-17, IFN-g, and eotaxin levels in VKC patients were significantly higher than those in controls (P , 0.05). IL-3, IL-4, IL-5, and TNFa levels tended to be higher in VKC patients. There was also statistically significant reduction from before 0.05% cyclosporine A treatment to after treatment in tear levels of IL-4, IL-5, IL-17A, TNFa, IFN-g, and eotaxin (P , 0.05). IL-2 and sIL-2R levels tended to be lower than pretreatment levels. Conclusions: Topical 0.05% cyclosporine A is effective in alleviating signs and symptoms of VKC patients and shows its effect probably by decreasing the local production of some inflammatory mediators in tears.
International Journal of Molecular Sciences, 2015
Corneal infections are frequent and potentially vision-threatening diseases, and despite the significance of the immunological response in animal models of microbial keratitis (MK), it remains unclear in humans. The aim of this study was to describe the cytokine profile of tears in patients with MK. Characteristics of ocular lesions such as size of the epithelial defect, stromal infiltration, and hypopyon were analyzed. Immunological evaluation included determination of interleukine (IL)-1β, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor (TNF)-α in tear samples obtained from infected eyes of 28 patients with MK and compared with their contralateral non-infected eyes. Additionally, frequency of CD4 + ,