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-8697046-B2
Publication Date
2014-04-15
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 fluid absorption activity of IFNγ is effective to remove excess fluid from the subretinal space and treat adverse ocular conditions associated with the accumulation of fluid in this space.
The problem being solved is the accumulation of subretinal fluid, which occurs in connection with numerous adverse ocular conditions such as retinal detachment, chronic macular edema, age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis. Dysfunction of RPE cells causes impairment of the blood-retinal barrier and contributes to fluid accumulation. There is a need for methods to remove fluid from the subretinal space to treat these conditions.
Applicants have discovered that IFNγ increases fluid transport from the neuroretina side of the RPE to the choroidal side, leading to absorption of excess fluid from the subretinal space. This activity is mediated via IFNγ interaction with its receptor localized primarily on the basolateral membrane of the RPE. The IFNγ-induced fluid transport is inhibited by an anti-IFNγ receptor antibody, JAK inhibitors, CFTR inhibitors, protein synthesis inhibitors, and protein kinase A (PKA) inhibitors, indicating the involvement of the JAK/STAT pathway, CFTR channels, protein synthesis, and PKA activation in the mechanism.
Claims Coverage
The patent includes three independent claims covering methods for treating visual acuity decrease, treating specific ocular diseases involving subretinal fluid accumulation, and decreasing fluid amount in the subretinal space by topical ocular instillation of interferon-gamma.
Treatment of decreased visual acuity by topical ocular instillation of interferon-gamma
A method for treating decreases in visual acuity associated with diseases or disorders causing accumulation of fluid in the subretinal space by administering interferon-gamma via topical ocular instillation in an amount effective to decrease the fluid in the subretinal space.
Treatment of ocular diseases causing subretinal fluid accumulation
A method for treating age-related macular degeneration, chronic macular edema, diabetic retinopathy, retinal detachment, glaucoma, or uveitis by decreasing fluid in the subretinal space through topical ocular instillation of interferon-gamma in effective amounts.
Decreasing subretinal fluid by topical interferon-gamma instillation
A method for decreasing fluid in the subretinal space of a patient by administering interferon-gamma via topical ocular instillation in an amount effective to reduce such fluid, including administration to the basolateral side of the RPE by anterior surface application.
The independent claims cover methods of decreasing subretinal fluid and treating associated ocular diseases by topical ocular instillation of interferon-gamma, emphasizing administration to the basolateral side of the retinal pigment epithelium and specifying treatment of various ocular disorders and conditions linked to subretinal fluid accumulation.
Stated Advantages
Administration of IFNγ to the basolateral side of the RPE leads to increased fluid transport from the retinal to the choroidal side, resulting in absorption of excess fluid from the subretinal space.
The method provides a means to treat adverse ocular conditions associated with fluid accumulation, such as retinal detachment, macular edema, age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis.
The fluid transport stimulation by IFNγ offers a therapeutic effect for reducing subretinal fluid and improving diseases causing decreases in visual acuity.
The use of topical ocular instillation for administration allows non-invasive treatment routes, including application to the anterior surface of the eye.
Documented Applications
Treatment of decreases in visual acuity associated with diseases or disorders causing accumulation of fluid in the subretinal space.
Treatment of age-related macular degeneration, chronic macular edema, diabetic retinopathy, retinal detachment (including that caused by injury or surgery), glaucoma, uveitis, and peripheral vitreoretinopathy.
Reduction of fluid accumulation in the subretinal space in patients suffering from the above ocular diseases and disorders.
Administration of IFNγ by topical ocular instillation, subtenon injection, or subretinal injection to achieve fluid absorption from the subretinal space.
Use of IFNγ compositions in treatments for inherited retinal degenerations such as retinitis pigmentosa and other forms of uveitis and neovascular diseases of the eye.
Therapeutic methods combined with other therapies such as photodynamic therapy, laser photocoagulation, or intraocular pressure–reducing drugs.
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