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Application of met-RANTES in preparing medicine used for treating inherited retinal degeneration

A genetic and drug technology, applied in drug combinations, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve the problems of unclear expression and activation mechanism, uncertain oxidative damage response, etc., to achieve strong practicability, therapeutic Early intervention, simple results

Active Publication Date: 2013-10-23
北京同仁医学科技有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chemokines are important stimulatory factors for the activation of microglia, but the expression and activation mechanism of chemokine receptors in microglia and photoreceptor cells are still unclear, and it is not certain whether their activation will trigger oxidative damage responses

Method used

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  • Application of met-RANTES in preparing medicine used for treating inherited retinal degeneration
  • Application of met-RANTES in preparing medicine used for treating inherited retinal degeneration
  • Application of met-RANTES in preparing medicine used for treating inherited retinal degeneration

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1 Expression and localization of β-chemokine receptor in the retina of rd mice of different ages

[0060] 1) Preparation of animal and tissue slices:

[0061] 350 male rd mice and 350 normal C57BL / 6N mice. 8 days, 10 days, 12 days, 14 days, 16 days and 18 days after birth of rd mice, 12 eyeballs of 6 rd mice were taken for detection, and the same number of mice of the same age and the same species were used as controls. After the mice were killed by neck dislocation, the eyeballs were quickly removed for tissue sections or the retinas were collected for molecular biology testing. Tissue sections were frozen and fixed in cold acetone for immunofluorescent staining.

[0062] 2) RT-PCR and immunofluorescence were used to detect the changes in the expression levels and cell localization of retinal CCR1, CCR2, CCR3 and CCR5 during the degeneration of photoreceptor cells in rd mice.

[0063] RT-PCR: The extraction of total RNA from fresh retinas of rd mice and co...

Embodiment 2

[0070] Example 2 Mechanism of Oxidative Damage in Microglia or Photoreceptor Cells after β Chemokine Receptor Activation

[0071] This example demonstrates the oxidative damage response that occurs after the activation of microglial cells or photoreceptor cell β chemokine receptors, which generate extracellular or intracellular ROS (including NO) respectively, thereby causing photoreceptor cell apoptosis.

[0072] 1. Immunohistochemistry: detection of iNOS and gp in retinal degeneration of rd mice 91phox organization expression. Frozen sections were dried naturally. 3%H 2 o 2 The solution was incubated at room temperature for 30 min to block endogenous peroxidase. Normal secondary antibody serum working solution was blocked and incubated at room temperature for 15 minutes. mouse anti-mouse gp 91phox Monoclonal antibody (1:500, Signal Transduction Laboratory) or rabbit anti-mouse iNOS (1:100, Santa Cruz Biotechnology) was incubated overnight at 4°C, and PBS was used ins...

Embodiment 3

[0095] Example 3 Study on the protection of photoreceptor cells and the therapeutic effect of met-RANTES on retinal degeneration in vivo and in vitro

[0096] 1. Study on the protection of photoreceptor cells and the therapeutic effect of met-RANTES on retinal degeneration in vivo

[0097] 1) Systemic administration

[0098] In view of the fact that document 6 confirmed that rd mice were born on the 8th day of birth as the initial period of β chemokine expression, this example selected rd mice on the 7th day after birth to compare and study the protective effect of intraperitoneal injection of met-RANTES in PBS solution on photoreceptor cells and Its therapeutic effect on retinal degeneration.

[0099] The experiment set up a control group and a treatment group, and each group consisted of 6 rd mice born on the seventh day after birth. Among them, the control group was intraperitoneally injected with 0.2ml PBS; the treatment group was intraperitoneally injected with 0.2ml ...

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Abstract

The invention relates to an application of a beta chemokine receptor inhibitor or a composition comprising the beta chemokine receptor inhibitor in preparing a medicine used for treating inherited retinal diseases or for protecting inherited retinal degeneration photoreceptor cells. The beta chemokine receptor inhibitor blocks the combination of beta chemokine and the receptor thereof, and further blocks the signaling pathways after receptor activation and the caused oxidative damage reaction, so as to treat the inherited retinal diseases or to protect the inherited retinal degeneration photoreceptor cells. Preferably, the beta chemokine receptor inhibitor is administrated through vitreous cavity injection. Preferably, the beta chemokine receptor inhibitor is selected from met-RANTES. Preferably, the disease is inherited retinal degeneration. The intervention of the beta chemokine receptor inhibitor against inherited retinal degeneration diseases is substantially made earlier. Therefore, the application is an ideal means for treating early-stage RP. According to the application, a specific gene defect type is not considered. The beta chemokine receptor inhibitor provided by the invention has the advantages such as better practicality, wider application, and the like.

Description

technical field [0001] The invention belongs to the field of biotechnology related to receptor inhibitors, and specifically relates to the application of met-RANTES in the preparation of medicines for treating hereditary retinal degeneration or medicines for protecting photoreceptor cells. Background technique [0002] Primary retinitis pigmentosa (RP) is a group of hereditary blinding eye diseases characterized by progressive selective loss of photoreceptor cells, with an incidence rate of 1 / 3000-1 / 5000 Common cause of visual impairment. Nearly 50 gene mutations have been confirmed to cause RP, but because the mechanism of photoreceptor cell degeneration caused by gene defects is unclear, there is still no effective treatment for RP. [0003] rd mouse is a natural animal model for studying hereditary retinal degeneration, and some RP patients have the same gene defect as rd mouse. Due to the PDE-6B gene mutation, rd mice developed retinal degeneration 8-10 days after birt...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K38/16A61P27/02
Inventor 曾惠阳陈星星刘谦陈艳邵长俊王沿强
Owner 北京同仁医学科技有限责任公司
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