IL1β, IL6 and IL8 gene polymorphisms involvement in recurrent corneal erosion in patients with hereditary stromal corneal dystrophies

Kucherenko, A. M.; Pampukha, V. M.; Drozhzhyna, G.; Лившиц, Л. А.

doi:10.3103/s0095452713030055

Cited by 3 publications

(4 citation statements)

References 18 publications

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“…26 IL6 gene expression also appeared to correlate moderately with CFS, but its low level of expression (in the cornea at day 10) might not suggest a pivotal role of IL6 overexpression in the worsening of CFS, although the IL6 gene was described to be implicated in corneal inflammation 56 and corneal erosion. 57 The levels of expression of IL1B, IL1RN, TLR1, TLR2, and TLR3 were quite low in untreated DED mice cornea, suggesting that their impact on corneal epithelium damage might be limited. The TNF gene, which had higher expression in DED mice cornea ( Table 2) and was downregulated (although not significantly) in the 0.1% and 1% CsA treatment groups as well as in the 0.5% LE group, did not significantly correlate with the CFS score.…”

Section: Discussionmentioning

confidence: 92%

Modulation of Inflammation-Related Genes in the Cornea of a Mouse Model of Dry Eye upon Treatment with Cyclosporine Eye Drops

Daull

Barabino

Feraille³

et al. 2019

Current Eye Research

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Purpose/Aim: Inflammation is recognized as playing an etiological role in dry eye disease. This study aimed to assess the efficacy of various topical cyclosporine A (CsA) formulations on cornea inflammatory markers in a mouse model of dry eye. Material and Methods: Six-to 7-week-old mice treated with scopolamine were housed in a controlled environment room to induce dry eye. Following dry eye confirmation by corneal fluorescein staining (CFS), the mice were treated three times a day with: 0.05%CsA (Restasis, Allergan), 0.1%CsA (Ikervis, Santen), 1%CsA oil solution, and 0.5% loteprednol etabonate (LE, Lotemax, Baush+Lomb), or left untreated. Aqueous tear production and CFS scores were assessed during the treatment period, and corneas were collected to measure the expression profile of a selection of inflammatory genes. Results: After 7 days of treatment, the CFS scores were reduced by 21%, 31%, and 44% with 0.05%CsA, 0.1%CsA, and 1%CsA eye drops, respectively. By contrast, 0.5% LE did not decrease corneal fluorescein staining at day 10. A statistically significant dose-dependent CFS reduction was observed only between the 0.05% and 1%CsA formulations. The gene expression profiles indicated that 12, 18, 17 genes were downregulated by 0.05%CsA, 0.1%CsA, 1%CsA, respectively. Among them, the genes significantly downregulated were: IL1A, IL1R1, and TLR4 with 0.05%CsA; H2-Eb1, IL1A, IL1B, IL1RN, IL6, TGFB2, TGFB3, TLR2, TLR3, and TLR4 with 0.1%CsA; IL1B, IL6, TGFB3, and TLR4 with 1%CsA. TGFB1 and TGFBR1 were the only genes upregulated in all groups, but only TGFB1 upregulation reached significance. IL6RA was significantly upregulated by 0.05%CsA. Conclusions: This study indicates that the three CsA formulations effectively modulated TLR4, TGFβ1, IL1, and IL6 pathways to reduce corneal epithelium lesions in a mouse model of severe dry eye. The study also suggests that the different anti-inflammatory eye drops modulated inflammatory genes in a slightly different manner. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 92%

Modulation of Inflammation-Related Genes in the Cornea of a Mouse Model of Dry Eye upon Treatment with Cyclosporine Eye Drops

Daull

Barabino

Feraille³

et al. 2019

Current Eye Research

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“…Seven studies were then excluded due to insufficient genotypic or allelic data. Finally, 23 studies investigating the association between IL-6-174 G/C polymorphism and ocular disease were included in this meta-analysis 15 – 37 (Fig. 1 A).…”

Section: Resultsmentioning

confidence: 99%

“…The highly frequent IL-6-174 G/C (rs1800795) polymorphism is of particular importance, due to its functional effect on IL-6 promoter activity, which then influences basal IL-6 levels 10 – 14 . Several studies have also reported the association between IL-6-174 G/C polymorphism with ocular diseases 15 – 37 . However, the results are equivocal, and the causal relationship between IL-6 gene mutations and ocular pathologies remain unclear.…”

Section: Introductionmentioning

confidence: 99%

The role of IL-6-174 G/C polymorphism and intraocular IL-6 levels in the pathogenesis of ocular diseases: a systematic review and meta-analysis

Ulhaq

Soraya

Budu

et al. 2020

Sci Rep

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Interleukin-6 (IL-6) is one of the key regulators behind the inflammatory and pathological process associated with ophthalmic diseases. The role of IL-6-174 G/C polymorphism as well as intraocular IL-6 levels among various eye disease patients differ across studies and has not been systematically reviewed. Thus, this study aims to provide a summary to understand the relationship between IL-6 and ophthalmic disease. In total, 8,252 and 11,014 subjects for IL-6-174 G/C and intraocular levels of IL-6, respectively, were retrieved from PubMed, Scopus and Web of Science. No association was found between IL-6-174 G/C polymorphisms with ocular diseases. Subgroup analyses revealed a suggestive association between the GC genotype of IL-6-174 G/C with proliferative diabetic retinopathy (PDR). Further, the level of intraocular IL-6 among ocular disease patients in general was found to be higher than the control group [standardized mean difference (SMD) = 1.41, 95% confidence interval (CI) 1.24–1.58, P < 0.00001]. Closer examination through subgroup analyses yielded similar results in several ocular diseases. This study thus indicates that the IL-6-174 G/C polymorphism does not predispose patients to ocular disease, although the GC genotype is likely to be a genetic biomarker for PDR. Moreover, intraocular IL-6 concentrations are related to the specific manifestations of the ophthalmic diseases. Further studies with larger sample sizes are warranted to confirm this conclusion.

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“…The interesting data prove the association between HD early manifestation and carrying substitution Ñ677Ò in MTHFR gene, involved in homocysteine metabolism [6]. We have also established that -174C allele of IL6 gene may be considered as a genetic marker of recurrent erosion development risk in patients with lattice SCD, whereas -781ÒT genotype of IL8 gene is associated with the absence of recurrent erosion in such patients [18].…”

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confidence: 53%

Human genome mutation and rearrangement studies – the way to investigate monogenic and complex disease pathogenesis

et al. 2013

Self Cite

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The summarized results of 25-year studies of department of human genomics of IMBG NASU are presented. The investigations were focused on identification of molecular genetic nature of human genome coding and non-coding region mutations (genetic polymorphisms) and rearrangements, their spectrum, and origin in Ukrainian population. The role of genome heterogeneity in some severe monogenic and complex disorder pathogenesis has been shown. The data concerning correlation between certain determinator gene mutations and phenotypical manifestation of most common in Ukraine monogenic diseases have been demonstrated. Moreover, the role of modifying genes in specific clinical phenotype variations has been shown. Origin of particular mutant alleles and main mechanisms of their frequency maintenance in Ukrainian population have been investigated. The data about association of some polymorphic variants with infertility, cardiovascular diseases (ischemic stroke) as well as mass infectious diseases (hepatitis C, AIDS) outcome and standard therapy efficiency have been presented. The first results and prospects for candidate genes of neurodegenerative disorders and intellectual disability search using whole genome CNVs screening are shown.

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IL1β, IL6 and IL8 gene polymorphisms involvement in recurrent corneal erosion in patients with hereditary stromal corneal dystrophies

Cited by 3 publications

References 18 publications

Modulation of Inflammation-Related Genes in the Cornea of a Mouse Model of Dry Eye upon Treatment with Cyclosporine Eye Drops

Modulation of Inflammation-Related Genes in the Cornea of a Mouse Model of Dry Eye upon Treatment with Cyclosporine Eye Drops

The role of IL-6-174 G/C polymorphism and intraocular IL-6 levels in the pathogenesis of ocular diseases: a systematic review and meta-analysis

Human genome mutation and rearrangement studies – the way to investigate monogenic and complex disease pathogenesis

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