Methods and compositions for preserving retinal ganglion cells

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...

AI Technical Summary

Benefits of technology

[0009]The invention is based, in part, on the discovery that a necrosis inhibitor, e.g., RIP kinase inhibitor, e.g., a necrostatin, e.g., necrostatin-1, can be used to reduce or prevent the loss of retinal ganglion cell viability, especially when the necrosis inhibitor is combined with an apoptotic inhibitor (e.g., a pan-caspase inhibitor, e.g., Z-VAD and/or IDN-6556). It was previously understood that retinal ganglion cell death associated with glaucoma and optic nerve injury was primarily caused by apoptosis. 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

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 c

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