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Application of IL-4 in preparation of medicine for treating retinal degenerative diseases

A technology of retinal degeneration and IL-4, applied in the application field of drugs for the treatment of retinal degenerative diseases, to achieve the effect of reducing folds, reducing retinal exudation, and increasing cell layer thickness

Pending Publication Date: 2022-03-29
ZHONGSHAN OPHTHALMIC CENT SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In retinal degenerative diseases, there is no report on the application of IL-4 as an active factor for treatment

Method used

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  • Application of IL-4 in preparation of medicine for treating retinal degenerative diseases
  • Application of IL-4 in preparation of medicine for treating retinal degenerative diseases
  • Application of IL-4 in preparation of medicine for treating retinal degenerative diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1 Construction of disease model

[0029] Sodium iodate (NaIO 3 ) is a stable oxidant that increases the conversion of glycine in melanocytes into glyoxylic acid, a cytotoxic compound, through a specific chemical reaction with melanin, so NaIO 3 RPE cells were selectively damaged, followed by secondary damage to photoreceptor cells, mimicking the pathological changes of retinal degeneration. Thereby the present invention adopts NaIO 3 Construction of related disease models. Specific steps are as follows:

[0030] (1) Dissolve IL-4 in phosphate buffered saline (PBS) to prepare a concentration of 2 μg / μL to obtain IL-4 solution for use;

[0031] (2) C57BL / 6J mice (purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd.) at 8-12 weeks were randomly divided into three groups, 10 in each group;

[0032] (3) Group 1 (blank group) was injected with PBS into the tail vein and 1 μL of PBS into the vitreous cavity at the same time; Group 2 (model group) was injec...

Embodiment 2

[0034] Example 2 Electroretinogram (ERG) to evaluate the retinal function of mice after IL-4 treatment

[0035] The whole process of the experiment was carried out under the condition of weak red light illumination.

[0036] (1) After Example 1 NaIO 3 On the 7th day after modeling, the electroretinogram (ERG) of the above-mentioned groups of mice was detected using an electroretinograph (Celeris-Diagnosyssystem). Mice were dark-adapted for 12 hours before examination. Intraperitoneal injection of 4.3% chloral hydrate (10mL / kg) for anesthesia, and compound tropicamide eye drops to dilate the pupils;

[0037] (2) Fix the mouse on the experimental board and install the electrodes. Drop a little methylcellulose on the cornea, stick the recording electrode (ring-shaped corneal electrode made of 0.2mm copper wire) on the corneal rim, and place the reference electrode (needle electrode) on the same side of the mouse’s cheek Subcutaneously, the ground electrode was placed under th...

Embodiment 3

[0040] Example 3 Optical coherence tomography (OCT) evaluation of retinal thickness in mice treated with IL-4

[0041] (1) After Example 1 NaIO 3 On the seventh day after modeling, the mice in the above groups were detected by OCT using an electroretinograph (SPECTRALIS-OCT, Heidelberg, Germany). Before the examination, 4.3% chloral hydrate (10mL / kg) was injected intraperitoneally for anesthesia, and compound tropicamide eye drops were used to dilate the pupils;

[0042] (2) After anesthesia, fix the head of the mouse on the proper position of the OCT jaw frame, clamp the bulbar conjunctiva with tweezers to rotate the eyeball position, and align the OCT detection light source with the laser spot area. Use the three-dimensional scanning method set in the computer to scan the laser spots, take the point 3mm away from the optic nerve head as the center of the circle, and scan with a radius of 1.5mm. The scanning range covers the four directions of the retina: transverse, longit...

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Abstract

The invention relates to application of IL-4 in preparation of drugs for treating retinal degenerative diseases. According to the method, ERG, OCT, fundus imaging and Hamp are adopted; experiments such as E and the like prove that the intravitreal injection of IL-4 can significantly reduce RPE cell damage of retinal degeneration mice, protect visual functions and delay retinal thinning. Immunofluorescence staining proves that IL-4 can act on an IL-4R alpha receptor of retinal pigment epithelium cells, and tight connection of RPE cells of a model mouse with retinal degeneration is regulated and controlled to be recovered. After IL-4 intervention, the expression level of RPE sclera complex inflammatory factors can be reduced, and anti-oxidative stress related genes are up-regulated, so that the oxidative stress state of retinal pigment epithelium is improved, and the death process of retinal photoreceptor cells is delayed. Experimental basis and theoretical basis are provided for treatment of the retinal degenerative diseases by the IL-4 and potential clinical application of the IL-4 as an immunomodulator, and the IL-4 has a wide application prospect in preparation of pharmaceutical preparations for treating the retinal degenerative diseases.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of IL-4 in the preparation of drugs for treating retinal degenerative diseases. Background technique [0002] Retinal degenerative diseases are a kind of refractory blinding eye diseases that seriously endanger human visual function, and have become increasingly prominent major blinding eye diseases in my country. Clinically, there is still no effective treatment. Dysfunction and loss of the retinal pigment epithelium (RPE) is a common pathological feature of these diseases. Previous studies have suggested that RPE cells participate in retinal pathophysiological processes through nutrition, barrier, phagocytosis, etc. Some RPE cells can express TLRs, Fc-γ and other immune-related receptors, mediate local immune responses, and affect cell survival and repair. Exploring the functional characteristics and repair potential of RPE from immune factors is...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/20A61P27/02A61P9/10
CPCA61K38/2026A61P27/02A61P9/10
Inventor 柳夏林何嫦周恬
Owner ZHONGSHAN OPHTHALMIC CENT SUN YAT SEN UNIV