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Method and preparation for regulating complement system, and use thereof

A complement system and receptor inhibitor technology, applied in the field of biomedicine, can solve problems such as drug resistance and short duration

Pending Publication Date: 2021-07-16
ZHONGSHAN OPHTHALMIC CENT SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the therapy is only effective in some patients and for a short duration, many patients require long-term, multiple injections of the drug into the vitreous, which often leads to drug resistance and other ocular complications

Method used

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  • Method and preparation for regulating complement system, and use thereof
  • Method and preparation for regulating complement system, and use thereof
  • Method and preparation for regulating complement system, and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] 1. Experimental construction method

[0044] 1) Using adeno-associated virus to construct a PDGF-D tissue-specific overexpression mouse model

[0045] a. Construct the adeno-associated virus (AAV) of RPE-specific overexpression: Utilize human VMD2 gene transcription initiation site upstream -598bp to +378bp sequence as retinal pigment epithelial cell (RPE) specific promoter, and utilize PDGF- The coding sequence of the D gene (NM_025208) was used as the target fragment to construct the vector and packaged into serotype 8 AAV. Store at -80°C.

[0046]b. Subretinal injection of AAV in mice: topical application of tropicamide for mydriasis, intraperitoneal injection of 4% chloral hydrate (10ml / kg body weight) for anesthesia, and then dripping procainamide for surface anesthesia of the cornea, and using Sodium carboxymethylcellulose prevents corneal desiccation. For subretinal injection, a sterile 5 μl syringe (Hamilton, CAT: 7633-01), 33-gauge needle (Hamilton, CAT: 780...

Embodiment 2

[0068] The experimental results of Example 1 show that the overexpression of PDGF-D induces inflammation and angiogenesis by activating the complement system. In the complement system, C3 is the most abundant and most important component. It is the two components of complement The central link of the main activation pathway is of great significance to the occurrence and development of inflammation. Studies have shown that whether in AMD patients or animal models, C3 increases significantly in the early process of the disease and returns to normal levels in the later stage, suggesting that the complement system plays an important role in regulating the pathological process of AMD. In this example, by constructing a laser-induced choroidal neovascularization (CNV) model commonly used in AMD, the effect of inhibiting the PDGF-D signaling pathway at different time points on the complement system, inflammation and angiogenesis in the experimental model was verified.

[0069] 1. Exp...

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Abstract

The invention provides a method and a preparation for regulating a complement system. An activation of the complement system is inhibited by inhibiting PDGF-D expression. The PDGF-D has a certain regulation effect on functions of the complement system, for example, when the PDGF-D is in an overexpression state, related genes (such as C1q and C3) of a complement pathway are up-regulated, such that inflammatory response is promoted and choroidal angiogenesis is induced. By inhibiting the overexpression of the PDGF-D, the activation of the complement system can be effectively inhibited, and further choroidal neovascularization and activation and migration of inflammatory cells are remarkably reduced.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a method, preparation and application for regulating the complement system. Background technique [0002] Platelet-derived growth factor-D (PDGF-D), one of the members of the platelet-derived growth factor (PDGF) family, exerts multiple functions in physiological and pathological conditions. Studies have shown that in the pathological process of many diseases, PDGF-D promotes inflammation and increases the migration of monocytes and macrophages. Inhibiting PDGF-D can alleviate pathological symptoms, such as inhibiting the infiltration of macrophages and reducing choroidal neovascularization. These studies highlight the effect of PDGF-D on immune cell infiltration under pathological conditions. However, how PDGF-D induces inflammatory cell activation and migration is not well understood. In addition, inhibiting PDGF-D with monoclonal antibody CR002 can reduce the depositi...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/7088A61K31/4709A61K39/395A61P29/00A61P27/02
CPCA61K45/00A61K31/7088A61K31/4709A61K39/395A61P29/00A61P27/02
Inventor 李旭日熊振
Owner ZHONGSHAN OPHTHALMIC CENT SUN YAT SEN UNIV
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