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Application of STING inhibitor in preparation of anti-filtration channel conjunctival cicatrization treatment medicine

A technology of 1. STING and 8. STING, applied in the preparation of anti-filtration tract conjunctival scarring treatment drugs, in the field of STING inhibitors, to relieve filtration tract conjunctival sac fibrosis and filtration tract scarring, and improve the efficiency of the invention. Effect

Active Publication Date: 2022-05-10
THE EYE HOSPITAL OF WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, H-151 has not been reported in the treatment of glaucoma with trabeculectomy for scarring of the filtering tract.

Method used

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  • Application of STING inhibitor in preparation of anti-filtration channel conjunctival cicatrization treatment medicine
  • Application of STING inhibitor in preparation of anti-filtration channel conjunctival cicatrization treatment medicine
  • Application of STING inhibitor in preparation of anti-filtration channel conjunctival cicatrization treatment medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Successfully established a scarring model of the filtering tract after trabeculectomy. The surgical method of trabeculectomy in mice refers to previous literature reports (Invest Ophthalmol Vis Sci. 2017, 58(9):3432-3439). After the operation, STING was injected into the conjunctival sac The specific small molecule inhibitor H151 was treated for 2 weeks, and 2 weeks after the operation, the mice were photographed under the operating microscope after anesthesia to observe the conjunctival filtering blebs of the mice.

[0022] Test procedure: Male C57BL / 6 mice were purchased from a commercial animal experiment center. Mice were housed in a thermostated 12-12h diurnal animal room with standard rodent chow and water. Animals were acclimatized to the environment one week before the start of the experiment. The H151 used in the experiment is a DMSO-soluble dosage form with a final concentration of 1 mg / kg. A mouse model of trabeculectomy with scarring of the filtering tract...

Embodiment 2

[0025] HTF cells were pre-incubated with H151 for 1 h, then stimulated with Ang II (1 μM) for 6 or 24 hours, and the effects of H151 on anti-Ang II were detected by fluorescent staining, quantitative fluorescence, RT-qPCR, Western Blot, and scratch experiments, respectively. .

[0026] Test procedure: HTF cells were pre-incubated with H151 (final concentration 1 μg / ml) for 1 hour, and stimulated with Ang II (1 μM) for 6 or 24 hours. (A, B) Immunofluorescence detection of αSMA expression level in trabeculectomy filtration channel of mice; (C) Western Blot detection of protein levels of Fibronectin and CTGF; (D, E) Real time qPCR detection of mRNA levels of Fibronectin and CTGF; ( F) Migration scratch test was used to detect the migration ability of HTF cells; (G) CCK8 was used to detect the cell proliferation ability. ** p < 0.01, *** p < 0.001, Ctrl vs Ang II; ## p < 0.01, ### p < 0.001, Ang II vs Ang II + H151.

[0027] Such as figure 2 As shown in A and B, it can be foun...

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Abstract

The invention relates to application of an STING inhibitor in preparation of a medicine for treating filter channel conjunctival scar, which finds that H151 can inhibit fibrosis, proliferation and migration capabilities of HTF cells induced by angiotensin II, and further inhibit activation of TBK1 and IRF3 mediated by STING and transcriptional activity of a transcription factor NF-kappa B, so as to relieve filter channel conjunctival sac fibrosis and filter channel scar. The long-term postoperative effective rate of glaucoma trabecula is improved.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of STING inhibitors in the preparation of anti-filtering conjunctival scarring therapeutic drugs. Background technique [0002] Glaucoma is a disease that causes irreversible degenerative changes in the optic nerve due to pathological changes in intraocular pressure. It is the world's first irreversible blinding eye disease. Glaucoma trabeculectomy is currently the most classic and widely used surgical method for the treatment of various types of glaucoma, which can effectively reduce the elevated intraocular pressure of glaucoma. According to previous studies, the early success rate of trabeculectomy was as high as 83% to 92%, but in the long-term follow-up process, this rate gradually decreased to 65%-44%. [0003] The main reason for the failure after trabeculectomy is the conjunctival scarring of the filtering tract, which leads to a decrease in the effec...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4045A61P27/02
CPCA61K31/4045A61P27/02Y02A50/30
Inventor 乐融融叶慧芳邵旭王庆陆欣蕾
Owner THE EYE HOSPITAL OF WENZHOU MEDICAL UNIV
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