Animal models, screening methods, and treatment methods for intraocular diseases or disorders
AssigneeZhuhai Qiwei Bio-Technology Ltd.
InventorsYan ZHANG, Lai WEI, Hui OUYANG
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Abstract
Provided herein are screening methods and animal models related to intraocular diseases such as age-related macular degeneration (AMD), for example, for identifying candidate therapeutics for treating or preventing eye diseases, such as AMD. Also provided herein are compounds/compositions that are useful for killing or inhibiting the growth of a microorganism, such as Bacillus megaterium. Further provided herein are methods of using the compounds/compositions for treating infections with a microorganism, such as Bacillus megaterium and for treating or preventing diseases or disorders associated with such infections, such as AMD.
Claims70
A screening method comprising:
- a) Culturing a microorganism in a suitable culture medium in the presence of a test compound;
- b) Measuring the growth of the microorganism in the culture medium in the presence of the test compound;
- and optionally
- c) Identifying a candidate therapeutics that inhibits the growth of the microorganism compared to a control,
- wherein the microorganism comprises a species that is enriched in the intraocular space (e.g., aqueous humor in anterior chamber, a suspensory ligament, ciliary body, ciliary body and muscle, vitreous humor in posterior chamber, retina, choroid, optic nerve, lens, or iris) in a subject having age-related macular degeneration (AMD) compared to a healthy subject.
A screening method comprising:
- a) Determining or having determined one or more microbial species as enriched in the intraocular space in a subject having age-related macular degeneration (AMD) compared to a healthy subject;
- b) Culturing a microorganism comprising at least one of the enriched microbial species in a suitable culture medium in the presence of a test compound;
- c) Measuring the growth of the microorganism in the culture medium in the presence of the test compound;
- and optionally
- d) Identifying a candidate therapeutics that inhibits the growth of the microorganism compared to a control.
A method of preparing an animal model, the method comprising introducing a microorganism and/or inactivated protein therefrom to an intraocular space of an eye of an animal, wherein the microorganism comprises a species that is enriched in the intraocular space in a subject having age-related macular degeneration (AMD) compared to a healthy subject.
Use of an effective amount of an antibiotic for the treatment or prevention of AMD in a subject, wherein the subject is identified as being infected with one or more species selected from Staphylococcus epidermidis, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus haemolyticus, Pseudomonas putida, Stenotrophomonas maltophilia, Bacillus cereus, Bacillus megaterium, Lactobacillus reuteri, Gardnerella vaginalis, Enterococcus faecium, Cytophaga hutchinsonii, Bacillus licheniformis, and Xanthomonas oryzae, e.g., in the intraocular space.
Use of an effective amount of an antibiotic for the treatment of a drusen symptom (e.g., soft drusen) in a subject in need thereof.
Use of an effective amount of an antibiotic for reducing a drusenoid lesion, drusen-like nodules, pyroptosis of the retinal pigment epithelium cells in the eye;
- activation of the complement system and/or inflammation in the eye, and/or secretion of active IL-10 and/or IL-18 by retinal pigment epithelium cells in the eye, in a subject in need thereof.
A method for screening a compound or combination of compounds for efficacy in treating or preventing an ocular disease, comprising:
- obtaining a sample taken from aqueous humor or vitreous humor of a subject selected from a subject having the ocular disease, a family member or close genetic relation of a subject having the ocular disease, or a deceased subject known to have had the ocular disease;
- culturing one or more organisms in the sample under conditions that mimic human intraocular space or in cooked meat medium to produce one or more cultures;
- adding the compound or combination of compounds to the one or more cultures;
- and
- determining whether the compound or combination of compounds reduces growth or reduces population of the one or more cultures,
- wherein the ocular disease is age-related macular degeneration (AMD).
A method for screening a compound or combination of compounds for efficacy in treating or preventing age-related macular degeneration (AMD), comprising:
- culturing one or more organisms under conditions that mimic human intraocular space or in cooked meat medium to produce one or more cultures, wherein the one or more organisms are selected from the group consisting of Staphylococcus epidermidis, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus haemolyticus, Pseudomonas putida, Stenotrophomonas maltophilia, Bacillus cereus, Bacillus megaterium, Lactobacillus reuteri, Gardnerella vaginalis, Enterococcus faecium, Cytophaga hutchinsonii, Bacillus licheniformis, Xanthomonas oryzae, and combinations thereof;
- adding the compound or combination of compounds to the one or more cultures;
- and
- determining whether the compound or combination of compounds reduces growth or reduces population of the one or more cultures.
A method for producing a mammalian model of age-related macular degeneration (AMD), comprising:
- introducing one or more microorganisms and/or one or more inactivated proteins of the one or more microorganisms into an eye of a mammal, thereby generating the mammalian model.
Use of a therapeutically effective amount of a compound of Formula I (e.g., Formula I-1, Formula I-2, Formula I-3, Formula I-4, Formula I-5), Formula II (e.g., Formula II-1, Formula II-2, Formula II-3, Formula II-4, Formula II-5, Formula II-6, Formula II-7, Formula II-8, Formula II-9, Formula II-10), Formula III (e.g., Formula III-1, Formula III-2, Formula III-3), Formula IV-1 or IV-2 (e.g., Formula IV-3, Formula IV-4, Formula IV-5, Formula IV-6), a glycoside (e.g., Formula V), wherein the aglycone of the glycoside is a phenolic compound, a flavonoid, a coumarin, a benzoic acid, or a sterol, or a pharmaceutically acceptable salt or ester thereof, or a pharmaceutical composition comprising the compound or pharmaceutically acceptable salt or ester thereof, for the treatment or prevention of age-related macular degeneration (AMD) in a subject in need thereof, wherein the Formula I, II, III, IV-1, IV-2, V, and subformulae thereof are defined herein.
Use of a therapeutically effective amount of a compound selected from compounds 1-8 or a pharmaceutically acceptable salt or ester thereof, or a pharmaceutical composition comprising the compound or pharmaceutically acceptable salt or ester thereof, for treating or preventing age-related macular degeneration (AMD) in a subject in need thereof, wherein compounds 1-8 have the following chemical structure:
Use of an effective amount of an antibiotic or a pharmaceutically acceptable salt thereof for killing or inhibiting growth of a microorganism, such as Bacillus megaterium, treating an infection (e.g., ocular infection, such as in the intraocular space) with a microorganism, and/or treating or preventing age-related macular degeneration (AMD) in a subject in need thereof.
Use of a therapeutically effective amount of an extract for killing or inhibiting growth of a microorganism, such as Bacillus megaterium, treating an infection (e.g., ocular infection, such as in the intraocular space) with a microorganism, and/or treating or preventing age-related macular degeneration (AMD) in a subject in need thereof, wherein the extract is an extract from one or more TCMs selected from Licorice (e.g., Glycyrrhiza uralensis), White Peony Root (e.g., Cynanchum otophyllum), Forsythia (e.g., Forsythia suspense), Fructus Aurantii (e.g., Citrus aurantium L.), Rehmannia glutinosa (e.g., Rehmannia glutinosa Libosch), Tangerine Peel (e.g., Citrus reticulata Blanco), and Notoginseng (e.g., Panax notoginseng).
Dependencies are inferred from the claim text.