# US 2008/0188573 A1 · Use of thy1-fp transgenic mouse for the identification of ophthalmic agents

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- Number: US 2008/0188573 A1
- Document ID: US20080188573A1
- Status: Published application
- Kind: A1
- Application number: 12/025,515
- Filed: 2008-02-04
- Published: 2008-08-07
- Earliest claimed: 2007-02-02
- Assignees: Alcon Research, Ltd.
- Inventors: Ji-Ye WEI; Richard L. ORNBERG; Gustav GRAFF
- Web page: https://patentgrep.com/patent/US20080188573A1

## CPC

- A61K 49/0008: {Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure}
- A01K 67/0275: Genetically modified vertebrates, e.g. transgenic
- A01K 2217/052: inducing gain of function
- A01K 2227/105: Murine
- A01K 2267/03: Animal model, e.g. for test or diseases
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS

## Abstract

The present invention relates to the use of thy1-FP (fluorescent protein) non-human transgenic animals such as mice to screen for ophthalmic agents that can be used to treat corneal dry eye syndrome and/or retinal neuropathies associated with glaucoma and/or age-related macular degeneration. Such ophthalmic agents may be selected by assessing their ability to provide protection in ocular tissue.

## Claims

### Claim 1

A method of manufacturing a topical ophthalmic agent comprising the steps of:
(a) providing a non-human transgenic animal that selectively expresses a fluorescent protein (FP) in ocular tissue;
(b) providing a candidate substance suspected of providing protection to ocular nervous tissue;
(c) administering the candidate substance to the animal;
(d) selecting the agent by assessing the ability of the candidate substance to provide protection in ocular nervous tissue; and
(e) manufacturing the selected ophthalmic agent.

### Claim 2 (depends on 1)

The method of claim 1, wherein the FP is green fluorescent protein (GFP).

### Claim 3 (depends on 1)

The method of claim 1, wherein the FP is yellow fluorescent protein (YFP).

### Claim 4 (depends on 1)

The method of claim 1, wherein the FP expression is driven by a neuron-specific promoter.

### Claim 5 (depends on 4)

The method of claim 4, wherein the neuron-specific promoter is Thy-1.

### Claim 6 (depends on 1)

The method of claim 1, wherein the ocular nervous tissue is corneal tissue or retinal tissue.

### Claim 7 (depends on 1)

The method of claim 1, wherein protection is measured by a decrease in the degeneration of ocular related neurons.

### Claim 8 (depends on 7)

The method of claim 7, wherein the neurons are retinal ganglion or optic nerve axons.

### Claim 9 (depends on 1)

The method of claim 1, wherein protection is measured by an increase in tear film secretion.

### Claim 10 (depends on 1)

A method of treating a subject suffering from or suspected of suffering from glaucoma comprising administering an effective amount of the agent identified in claim 1.

### Claim 11 (depends on 1)

A method of treating a subject suffering from or suspected of suffering from age-related macular degeneration comprising administering an effective amount of the agent identified in claim 1.

### Claim 12 (depends on 1)

A method of treating a subject suffering from or suspected of suffering from dry eye syndrome in at least one eye comprising administering an effective amount of the agent identified in claim 1.

### Claim 13

A method of screening an agent for its efficacy in ameliorating the symptoms of dry eye syndrome, comprising administering a candidate agent to a non-human transgenic animal expressing a fluorescent protein product, and comparing the symptoms of dry eye syndrome in the non-human transgenic animal to one or more control animals, wherein a decrease in symptoms of dry eye syndrome in the animal treated with the test agent indicates efficacy of the agent.

### Claim 14 (depends on 13)

A method of treating a subject suffering from dry eye syndrome comprising administering the agent identified in claim 13.

### Claim 15 (depends on 14)

The method of claim 14, wherein said dry eye syndrome is in at least one eye of the subject.

### Claim 16 (depends on 13)

A method of treating a subject suspected of suffering from dry eye syndrome comprising administering the agent identified in claim 13.

### Claim 17

A method of screening an agent for its efficacy in ameliorating the symptoms of glaucoma, comprising administering a candidate agent to a non-human transgenic animal expressing a fluorescent protein product, and comparing the symptoms of glaucoma in the non-human transgenic animal to one or more control animals, wherein a decrease in symptoms of glaucoma in the animal treated with the test agent indicates efficacy of the agent.

### Claim 18 (depends on 17)

A method of treating a subject suspect of suffering from glaucoma comprising administering the agent identified in claim 17.
