Methods of administering interferon gamma to absorb fluid from the subretinal space
Inventors
Li, Rong • Miller, Sheldon S. • Maminishkis, Arvydas
Assignees
US Department of Health and Human Services
Publication Number
US-9486502-B2
Publication Date
2016-11-08
Expiration Date
2029-08-14
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Abstract
Particular aspects of the invention provide methods for decreasing the amount of fluid present in the subretinal space of the eye by administering interferon gamma to the basolateral side of the retinal pigment epithelium. Adverse ocular conditions associated with the accumulation of fluid in the subretinal space can be treated by administering an amount of interferon gamma to the basolateral side of the retinal pigment epithelium effective to remove excess fluid from the subretinal space.
Core Innovation
The invention provides methods for decreasing the amount of fluid present in the subretinal space of the eye by administering interferon gamma (IFNγ) to the basolateral side of the retinal pigment epithelium (RPE). This administration of IFNγ increases fluid transport across the RPE from the neuroretina side to the choroidal side, effectively absorbing excess fluid from the subretinal space. The methods also include treating adverse ocular conditions associated with fluid accumulation in the subretinal space, such as decreases in visual acuity caused by various ocular diseases and disorders.
The problem addressed by the invention is the accumulation of fluid in the subretinal space, which is associated with numerous adverse ocular conditions including retinal detachment, chronic macular edema, age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis. Dysfunction of the RPE, which regulates transport of fluids and nutrients between the retina and choroid, plays a key role in this pathology. Prior to this invention, there was a need to elucidate if IFNγ affects RPE function in a way that could be used to treat such conditions. The invention solves this problem by demonstrating that administration of IFNγ to the basolateral side of the RPE enhances fluid absorption from the subretinal space, thereby providing a therapeutic approach to these ocular conditions.
The invention also encompasses formulations of IFNγ suitable for administration to the eye, including aqueous solutions, gels, and gel-like formulations, which can be applied topically to the anterior surface of the eye, or administered by subtenon or subretinal injections. The methods cover administering effective amounts of IFNγ to reduce subretinal fluid, improve visual acuity, and treat diseases like age-related macular degeneration, diabetic retinopathy, inherited retinal degeneration, glaucoma, uveitis, and retinal detachment caused by injury or surgery.
Claims Coverage
The patent contains multiple independent claims defining inventive methods related to the administration of interferon-gamma for ophthalmic treatment, each focused on specific treatment indications, administration methods, and combinations with other therapies.
Treatment of decreased visual acuity associated with retinal or choroidal neovascularization by topical ocular instillation of interferon-gamma
A method of treating decreased visual acuity linked to retinal or choroidal neovascularization through topical ocular instillation of interferon-gamma, administering an amount effective to decrease fluid in the subretinal space.
Administration of interferon-gamma to the basolateral side of the retinal pigment epithelium
Delivering interferon-gamma specifically to the basolateral side of the retinal pigment epithelium, including administration via the anterior surface of the eye, at doses ranging about 5 ng/ml to 100 mg/ml.
Use of interferon-gamma in treatment of inherited retinal degenerations by reducing subretinal fluid
A method treating inherited retinal degenerations (such as retinitis pigmentosa, Bardet-Biedl syndrome, Leber congenital amaurosis, etc.) by administering interferon-gamma topically to the eye at an amount effective to reduce subretinal fluid accumulation.
Treatment of fluid accumulation in subretinal space caused by MAPK pathway blockers using interferon-gamma
Administering interferon-gamma topically to treat fluid accumulation in the subretinal space caused by mitogen-activated protein kinase (MAPK) signaling pathway blockers in retinal pigment epithelial cells.
Combination therapies including interferon-gamma with other ocular treatments
Methods where interferon-gamma is administered to the patient in combination with other active agents or therapeutic regimens such as photodynamic therapy, laser photocoagulation, or intraocular pressure reducing drugs.
The independent claims collectively cover methods of treating subretinal fluid accumulation and associated visual impairment by administering interferon-gamma to the posterior eye structures, focusing on basolateral application to the retinal pigment epithelium and encompassing a range of ocular diseases, administration forms, dosages, and combination therapies.
Stated Advantages
Interferon gamma increases fluid transport across the retinal pigment epithelium, effectively absorbing excess fluid from the subretinal space.
Administration of interferon gamma to the basolateral side of the retinal pigment epithelium presents a novel method to treat various ocular conditions involving fluid accumulation.
The therapy can be delivered non-invasively via topical ocular instillation, offering a potentially safer and more convenient treatment option.
Interferon gamma treatment results in decreased fluid accumulation in the subretinal space, which addresses the underlying cause of vision loss in diseases such as macular degeneration, diabetic retinopathy, and retinal detachment.
Documented Applications
Treatment of decreases in visual acuity associated with diseases causing accumulation of fluid in the subretinal space such as age-related macular degeneration, chronic macular edema, diabetic retinopathy, glaucoma, uveitis, peripheral vitreoretinopathy, and retinal detachment caused by retinal injury or surgery.
Treatment of inherited retinal degenerations including retinitis pigmentosa, Bardet-Biedl syndrome, Leber congenital amaurosis, cone or cone-rod dystrophy, congenital stationary night blindness, macular degeneration, optic atrophy, syndromic or systemic retinopathy, and usher syndrome.
Treatment of neovascular eye diseases such as wet age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity via reduction of subretinal fluid.
Topical ocular instillation of interferon gamma for treating cystoid macular edema (CME) secondary to uveitis in human patients.
Use in combination with other therapies such as photodynamic therapy, laser photocoagulation, and intraocular pressure reducing drugs for ocular diseases involving fluid accumulation.
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