The Effect of TNF-α Blocker HL036337 and Its Best Concentration to Inhibit Dry Eye Inflammation

Choi, Wungrak; Noh, Han-Jin; Yeo, Areum; Jang, Hanmil; Ahn, Hyea Kyung; Song, Yeon Jung

doi:10.3341/kjo.2016.30.4.302

Cited by 24 publications

(18 citation statements)

References 22 publications

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“…This lack of correlation was unexpected, as the TNF protein is more likely to have a causative role in CFS worsening. 58 While all CsA treatments showed efficacy on CFS, the expression profiles of the inflammatory genes followed in this study tend to indicate that there were some differences in how the CsA-based formulations modulate these inflammatory genes. These differences might result from the difference in CsA concentration found in the three eye drops and from the difference in their vehicle composition too.…”

Section: Discussionmentioning

confidence: 68%

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: 68%

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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“…These indicates that IL-6α and TNF-α are the major factors affecting dry eye related inflammation and LLLT may reduce inflammation through controlling the level of TNF-α in its mechanism. 33,34 TNF-α, one of the most important pro-inflammatory cytokines, is known to be involved in various chemokine productions and the recruitment of macrophages, neutrophils, and T-cells at inflammation site to enhance inflammatory responses. 35 There is still a lack of studies regarding the relationship between LLLT and cytokine levels in ocular inflammation, but some studies on other tissues such as muscle and lung showed that LLLT is effective in reducing TNF-α expression and controlling the degree of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Effects of Low-level Light Therapy at 740 nm on Dry Eye Disease In Vivo

et al. 2019

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Background and ObjectivesLow-level light therapy (LLLT) is an application of low-power light for various purposes such as promoting tissue repair, reducing inflammation, causing analgesia, etc. A previous study suggested the effect of light emitting diode (LED) light with the wavelength of 740 nm for promoting wound healing of corneal epithelial cells. This current study aimed to confirm the effect of LLLT for managing inflammation of a dry eye disease (DED) mouse model. Materials and MethodsA total of 50C57BL/6 female mice were randomly grouped into 5 groups to compare the effect of LLLT:1) Control group, 2) Only LLLT group, 3) Dry eye group, 4) LLLT in dry eye group, and 5) Early treatment group. DED was induced with 4 daily injections of scopolamine hydrobromide and desiccation stress for 17 days, and LLLT at 740 nm was conducted once every 3 days. To analyze the effect of LLLT on the DED mouse model, tear volume, corneal surface irregularities, and fluorescence in stained cores were measured, and the level of inflammation was assessed with immunohistochemistry. ResultsThe DED mouse model showed significant deterioration in the overall eye condition. After LLLT, the amount of tear volume was increased, and corneal surface irregularities were restored. Also, the number of neutrophils and the level of inflammatory cytokines significantly decreased as well. ConclusionThis study showed that LLLT at 740 nm was effective in controlling the corneal conditions and the degree of inflammation in DED. Such findings may suggest therapeutic effects of LLLT at 740 nm on DED.

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“…In mouse models, the lacrimal and submandibular glands are the first affected in the disease process, and several inflammatory mediators such as interleukin (IL)-1β, IL-6, IL-17, interferon-γ, TNF-α, chemokine ligand 2, and MMPs have been implicated in DED-associated inflammation 46 . TNF-α, as well known inflammatory cytokine, is involved in immune and inflammatory responses, and recently reported that inhibition of TNF-α can improve DED 47 . We also previously reported that desiccating stress promote the expression of TNF-α in lacrimal gland in NOD.B10.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory effect of hydroxyproline-GQDGLAGPK in desiccation stress-induced experimental dry eye mouse

Lee

Kim

Ahn

et al. 2017

Sci Rep

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The purpose of this study has been the investigation of the effect of novel peptide hydroxyproline-GQDGLAGPK (Hyp-GQDGLAGPK) in desiccation stress-induced dry eye mouse model and compared medicines for dry eye disease including cyclosporine, diquafosol and sodium hyaluronate. Seventy eight NOD.B10.H2 b mice were injected with scopolamine and exposed to an air draft for 10 days, and then the mice were treated with normal saline (n = 13), 1% Hyp-GQDGLAGPK (n = 13), 0.05% cyclosporine (n = 13), 3% diquafosol (n = 13), and 0.1% hyaluronate (n = 13) for 10 days. Thirteen mice were used for histopathologic analysis at DS 10d. The desiccation stress significantly decreased tear production, but the topical treatment of Hyp-GQDGLAGPK recovered to the baseline levels, which was similar to cyclosporine and diquafosol. In addition, Hyp-GQDGLAGPK improved facilitating epithelium stabilization including the corneal irregularity score, fluorescein score and detachment of the corneal epithelium. These improvements in stabilization of the corneal epithelium was superior to that in the cyclosporine and sodium hyaluronate groups. Furthermore, desiccation stress markedly induced expression of autoimmune inflammation-related factors in the lacrimal glands, but it was significantly suppressed by Hyp-GQDGLAGPK treatment. Overall, we found that novel peptide Hyp-GQDGLAGPK has multi-functional effects such as stabilizing the tear film and inhibiting inflammation.

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The Effect of TNF-α Blocker HL036337 and Its Best Concentration to Inhibit Dry Eye Inflammation

Cited by 24 publications

References 22 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

Effects of Low-level Light Therapy at 740 nm on Dry Eye Disease In Vivo

Anti-inflammatory effect of hydroxyproline-GQDGLAGPK in desiccation stress-induced experimental dry eye mouse

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