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Methods and compositions for preserving retinal ganglion cells

Inactive Publication Date: 2014-01-23
MASSACHUSETTS EYE & EAR INFARY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text describes a method for preserving the visual function of an eye affected with an ocular condition, such as glaucoma or optic nerve injury, by reducing the loss of retinal ganglion cells. The method involves administering a combination of a necrosis inhibitor and an apoptotic inhibitor to the eye. The use of both inhibitors prevents the loss of retinal ganglion cells and improves visual function relative to the eye prior to treatment. The method can be used to treat ocular conditions that result in the loss of retinal ganglion cells, such as glaucoma or optic nerve injury.

Problems solved by technology

However, studies have shown that the administration of Z-VAD, an apoptosis inhibitor (i.e., a pan-caspase inhibitor), fails to thoroughly prevent retinal ganglion cell loss in glaucoma and optic nerve injury.
A symptom of the ocular condition may be the loss of retinal ganglion cells in the retina of the eye with the condition.

Method used

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  • Methods and compositions for preserving retinal ganglion cells
  • Methods and compositions for preserving retinal ganglion cells
  • Methods and compositions for preserving retinal ganglion cells

Examples

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example 1

Efficacy of a Necrosis Inhibitor and a Pan-Caspase Inhibitor in the Treatment of Glaucoma and Optic Nerve Injury

[0361]Glaucoma is a group of ocular disorders, characterized by optic nerve injury. In most cases of glaucoma, the optic nerve injury is caused by elevated intraocular pressure. Furthermore, higher intraocular pressures are generally associated with greater nerve damage. In this example, mouse models of optic nerve (ON) injury was used to assess the role of RIP-mediated programmed necrosis and apoptosis in this ocular disorder. Given that ON injury is a hallmark of glaucoma, this model also provided an assessment of RIP-mediated programmed necrosis in RGC loss in glaucoma.

A. Neutralization of TNF-α Prevents Optic Nerve Injury-Induced RGC Death

[0362]Recent evidence has demonstrated the role of TNF-αc as a mediator of retinal ganglion cell (RGC) death in glaucoma (Nakazawa et al., (2006) J NEUROSCI 26:12633-12641)). Furthermore, in the glaucomatous eye, death receptors of TN...

example 2

Efficacy of a Necrosis Inhibitor and a Pan-Caspase Inhibitor in Promoting RGC Survival and Axon Regeneration

[0390]Like most pathways in the mature central nervous system, the optic nerve cannot regenerate if injured, leaving victims of traumatic nerve injury or degenerative diseases such as glaucoma with life-long visual losses. This situation can be, at least, partially reversed by enhancing the intrinsic growth state of retinal ganglion cells (RGCs). In this example, the efficacy of necrosis inhibitor and a pan-caspase inhibitor in promoting RGC survival and axon regeneration is investigated using a mouse optic nerve crush model.

A. A Necrosis Inhibitor in Combination with a Caspase Inhibitor Promotes RGC Survival in a Optic Nerve Crush Model

[0391]Mice were subjected to optic nerve crush surgery. Specifically, animals were anesthetized with an intraperitoneal injection of ketamine (60-80 mg / kg: Phoenix Pharmaceutical, St. Joseph, Mo.) and xylazine (10-15 mg / kg: Bayer, Shawnee Missi...

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Abstract

Provided are methods and compositions for maintaining the viability of retinal ganglion cells in a subject with an ocular disorder including, for example, glaucoma and optic nerve injury. The viability of the retinal ganglion cells can be preserved by administering a necrosis inhibitor either alone or in combination with an apoptosis inhibitor to a subject having an eye with the ocular condition. The compositions, when administered, maintain the viability of the cells and / or promote axon regeneration, thereby minimizing the loss of vision or visual function associated with the ocular disorder.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of and priority to U.S. Provisional Application No. 61 / 409,055, filed Nov. 1, 2010; U.S. Provisional Application No. 61 / 414,862, filed Nov. 17, 2010; and U.S. Provisional Application No. 61 / 472,144, filed Apr. 5, 2011; the disclosures of each application are hereby incorporated by reference in their entirety.GOVERNMENT FUNDING[0002]The work described in this application was sponsored, in part, by the National Eye Institute under Grant No. EY14104. The United States Government has certain rights in the invention.FIELD OF THE INVENTION[0003]The field of the invention relates generally to methods and compositions for preserving the viability of retinal ganglion cells (RGCs), for example, in a subject affected with an ocular disorder wherein a symptom of the ocular disorder is loss of retinal ganglion cell viability. More particularly, the invention relates to the use of a necrosis inhibitor, e.g., a RIP ki...

Claims

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Application Information

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IPC IPC(8): A61K31/4178A61K38/00
CPCA61K31/4178A61K38/005A61K31/195A61K31/40A61K31/403A61K31/4166A61K38/06A61P27/02A61P27/06A61K2300/00A61K31/401A61K9/0048
Inventor VAVVAS, DEMETRIOSMILLER, JOAN W.KAYAMA, MAKI
Owner MASSACHUSETTS EYE & EAR INFARY
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