Non-human primate model of age-related macular degeneration and method for producing same
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Publication Number
US-10532112-B2
Publication Date
2020-01-14
Expiration Date
Abstract
An object of the present invention is to provide a method for producing a non-human primate model of AMD, a method for evaluating the efficacy of a test substance in the prevention or treatment of AMD using the AMD animal model produced according to this method, and a method for screening substances effective in the prevention or treatment of AMD using the aforementioned AMD animal model. The method for preparing the AMD animal model consists of administering sodium iodate into a vitreous body of a non-human primate, and the method for evaluating the efficacy of a test substance in the prevention or treatment of AMD consists of preparing a non-human primate model of AMD according to the aforementioned method for preparing an AMD animal model, and evaluating the efficacy of the test substance in the prevention or treatment of AMD using the resulting AMD animal model.
Core Innovation
The invention generates a non-human primate animal model of age-related macular degeneration (AMD) by administering sodium iodate into the vitreous body. In the resulting animal model, thinning of an outer nuclear layer (OLN) and degeneration of a retinal pigment epithelium (RPE) of the retina develop in the periphery of a central fossa of a macula in the vitreous body of the non-human primate, reproducing retinal pathology relevant to atrophic AMD.
The described approach is directed to producing an atrophic AMD model in a non-human primate while reproducing human-like retinal pathology, including geographic atrophy as part of the observed degeneration. The document further contrasts the pathology and evaluation context with a light-induced retinopathy reference model showing differing pathology.
The disclosed model is used to evaluate test substances for AMD by administering test substances to the primate AMD model and determining efficacy by improvement in AMD-related metrics, including ONL thinning, RPE degeneration, and geographic atrophy. The evaluation and screening context is supported by imaging and histological assessments, including OCT, fundus imaging, fundus autofluorescence, fluorescein angiography, and HE staining.
Claims Coverage
The independent claim defines a method for producing an animal model of AMD, and it is refined by multiple dependent claims that add specific inventive features.
Vitreous sodium iodate administration to produce an AMD model
Administering sodium iodate into a vitreous body of a non-human primate, and observing development of thinning of an outer nuclear layer (OLN) and degeneration of a retinal pigment epithelium (RPE) of a retina in the periphery of a central fossa of a macula, thereby producing an animal model of AMD.
Primate species limited to cynomolgus monkey or rhesus monkey
The method using a non-human primate selected as a cynomolgus monkey or a rhesus monkey.
Sodium iodate vehicle as water or phosphate-buffered saline
Administering sodium iodate in a sodium iodate solution selected from water or phosphate-buffered saline.
Geographic atrophy occurrence in the ocular fundus
An animal model in which geographic atrophy occurs in the ocular fundus of the resulting animal model of age-related macular degeneration.
Screening and selecting effective substances by reduced retinal degeneration versus pretreatment
Creating a non-human primate AMD model, evaluating a test substance’s treatment efficacy in that model, and selecting the test substance when retinal metrics show reduced ONL thinning and reduced RPE degeneration after treatment versus pre-treatment.
Constrained sodium iodate dosage per vitreous body
Administering sodium iodate at a dosage of 0.5 mg to 2.5 mg per vitreous body.
Overall, the claim set covers producing an AMD animal model in a non-human primate by vitreous sodium iodate administration with observed peripheral central-fossa changes (OLN thinning and RPE degeneration), optionally including geographic atrophy, and further includes screening and selection of test substances based on comparative reductions in ONL thinning and RPE degeneration versus pre-treatment, with additional limitations on primate species, vehicle, and dosage range.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Evaluating and screening test substances for AMD by administering the substances to the primate AMD model and determining efficacy based on improvement in AMD-related metrics (ONL thinning, RPE degeneration, and geographic atrophy).
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