Application of BRD4 inhibitor JQ1 in corneal scar inhibition

A corneal scar and corneal stroma technology, applied in the field of biomedicine, can solve the problems of corneal scar that is difficult to heal, curative effect and prognosis are not ideal

Active Publication Date: 2017-07-28
SHANDONG EYE INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Corneal scarring is a chronic disease that is difficult to cure. At present, there is no effective treatment for corneal scarring. Various treatment methods have been tried clinically, such as rapamycin, ...

Method used

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  • Application of BRD4 inhibitor JQ1 in corneal scar inhibition
  • Application of BRD4 inhibitor JQ1 in corneal scar inhibition
  • Application of BRD4 inhibitor JQ1 in corneal scar inhibition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1: To study the effect of adding JQ1 (Abcam, USA) on TGFβ-induced differentiation of human corneal stromal cells into HCF.

[0041] Use 2.4U / ml Dispase II (Roche, USA) to digest normal human corneal rings at 4°C (provided by the Eye Bank of Shandong Provincial Eye Institute, and the central cornea of ​​human cornea slices was used in this study after the clinical operation). Tear off the epithelial layer and endothelium under the microscope, remove the excess scleral tissue, cut the corneal tissue into 6-8 small pieces, digest in 1.25mg / ml collagenase at 37°C for 1 hour, collect the digested tissue pieces, and use D / F12+10% FBS (Gibco, USA) culture medium was resuspended and centrifuged, and inoculated into a culture dish, which was human keratocyte stromal cell (HCF) P0 generation cells, and 2000 P2-P4 generation HCF cells were inoculated in a 96-well plate, and one of them was selected. 1 well was used as a control, and 2ng / ml TGFβ was added to the remaining ...

Embodiment 2

[0045] Example 2: To study the effect of exogenously added JQ1 on corneal scarring.

[0046] 1. Establishment of mouse corneal scar model and the effect of JQ1 on corneal scar.

[0047] Twelve adult C57BL / 6 mice were used to scrape the epithelium in the central 3mm area of ​​the mouse right cornea with a 3mm trephine and an epithelial spatula, and the superficial stroma layer was scraped off with a razor blade to establish a corneal scar model. After 7 days, the mouse cornea Significant scars appeared, and the modeling mice were randomly divided into control group and experimental group, subconjunctival injection of 7μl JQ1 (concentration 500nM, mouse weight 25g / mouse) was used as the treatment group (PBS was the control group), and the scar treatment was observed by taking pictures after treatment situation results see image 3 ,like image 3 Significant scars appeared in the mouse cornea 7 days after modeling (upper left and upper right), and the scars in the treatment gro...

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Abstract

The invention provides application of a BRD4 inhibitor JQ1 in corneal scar inhibition. The application is characterized in that corneal stroma cells are allowed to contact with an effective-dose BRD4-expression-inhibiting reagent or a derivative thereof, or the effective-dose BRD4-expression-inhibiting reagent or the derivative thereof is provided for a subject. By allowing the corneal stroma cells to contact with the effective-dose BRD4-expression-inhibiting reagent or the derivative thereof, corneal scar formation can be reduced or corneal scars can be reversed, improved or treated. A medicinal small-molecule compound JQ1 for preventing or treating the corneal scars is provided by using BRD4 as the target, and the medicinal small-molecule compound JQ1 is applicable to the early intervening treatment of the corneal scars.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to the application of a BRD4 inhibitor JQ1 in the inhibition of corneal scars. Background technique [0002] Corneal scarring is a pathological change secondary to a variety of corneal diseases, and it is the direct cause of vision damage or even loss caused by many corneal diseases. Corneal tissue contains corneal epithelial cells, stromal cells, and endothelial cells. The epithelial cell layer of the cornea can quickly regenerate after damage, but the stroma layer and endothelial cell layer cannot regenerate after injury. Corneal opacity is caused after the cornea is healed from trauma and inflammatory scars , changes in refractive power, etc. After corneal injury, keratocytes die or switch to a repair phenotype that can regenerate keratocytes or lead to fibrotic scarring. During wound repair, corneal stromal cells around the injured site differentiate into myofibroblasts,...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61P27/02
CPCA61K45/00
Inventor 曲明俐周庆军陈敏张晓萍田乐
Owner SHANDONG EYE INST
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