Methods and compositions for preserving retinal ganglion cells
First Claim
1. A method of preserving visual function of an eye of a subject with an ocular condition selected from the group consisting of glaucoma, optic nerve injury, and optic neuritis, wherein a symptom of the ocular condition is the loss of retinal ganglion cell viability in the retina of the eye with the condition, the method comprising:
- (a) administering to the eye of the subject an effective amount of a necrosis inhibitor selected from the group consisting of necrostatin-1, necrostatin-2, necrostatin-3, necrostatin-4, necrostatin-5, necrostatin-7, and related compounds, and an effective amount of an apoptosis inhibitor selected from the group consisting of pan-caspase inhibitors, caspase-1 inhibitors, caspase-3 inhibitors, caspase-8 inhibitors, and caspase-9 inhibitors, thereby to preserve the viability of retinal ganglion cells disposed within the retina of the eye; and
(b) after step (a), measuring visual function of the eye.
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Accused Products
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.
26 Citations
26 Claims
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1. A method of preserving visual function of an eye of a subject with an ocular condition selected from the group consisting of glaucoma, optic nerve injury, and optic neuritis, wherein a symptom of the ocular condition is the loss of retinal ganglion cell viability in the retina of the eye with the condition, the method comprising:
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(a) administering to the eye of the subject an effective amount of a necrosis inhibitor selected from the group consisting of necrostatin-1, necrostatin-2, necrostatin-3, necrostatin-4, necrostatin-5, necrostatin-7, and related compounds, and an effective amount of an apoptosis inhibitor selected from the group consisting of pan-caspase inhibitors, caspase-1 inhibitors, caspase-3 inhibitors, caspase-8 inhibitors, and caspase-9 inhibitors, thereby to preserve the viability of retinal ganglion cells disposed within the retina of the eye; and (b) after step (a), measuring visual function of the eye.
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2. The method of claim 1, wherein, after administration of the necrosis inhibitor and the apoptosis inhibitor, the visual function of the eye is preserved or improved relative to the visual function prior to administration of the necrosis inhibitor and the apoptosis inhibitor.
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3. The method of claim 2, wherein the visual function is visual acuity.
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4. The method of claim 1, wherein the ocular condition is glaucoma.
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5. The method of claim 1, wherein the necrosis inhibitor is necrostatin-1.
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6. The method of claim 1, wherein the necrosis inhibitor is administered to provide a final concentration of necrosis inhibitor in the eye greater than about 10 μ
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7. The method of claim 1, wherein from about 0.05 mg to about 2 mg of necrosis inhibitor is administered.
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8. The method of claim 1, wherein the pan-caspase inhibitor is zVAD, IDN-6556 or a combination thereof.
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9. The method of claim 1, wherein from about 0.15 mg to about 1.5 mg of the pan-caspase inhibitor is administered.
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10. The method of claim 1, wherein the necrosis inhibitor, the apoptosis inhibitor, or both the necrosis inhibitor and the apoptosis inhibitor are administered to the eye.
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11. The method of claim 1, wherein the necrosis inhibitor, the apoptosis inhibitor, or both the necrosis inhibitor and the apoptosis inhibitor are administered by intraocular injection.
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12. The method of claim 11, wherein the necrosis inhibitor, the apoptosis inhibitor, or both the necrosis inhibitor and the apoptosis inhibitor are administered intravitreally.
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13. The method of claim 1, wherein the necrosis inhibitor, the apoptosis inhibitor, or both the necrosis inhibitor and the apoptosis inhibitor are administered sequentially or simultaneously.
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14. The method of claim 1, wherein the necrosis inhibitor is a compound of Formula I:
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15. The method of claim 1, wherein the necrosis inhibitor is a compound of Formula I-A:
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16. The method of claim 1, wherein the necrosis inhibitor is a compound selected from the group consisting of a compound of Formula I-B:
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17. The method of claim 1, wherein the necrosis inhibitor is a compound of Formula I-E:
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18. The method of claim 1, wherein the necrosis inhibitor is a compound of Formula II:
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19. The method of claim 1, wherein the necrosis inhibitor is a compound of Formula II-A:
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20. The method of claim 1, wherein the necrosis inhibitor is a compound of Formula III:
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21. The method of claim 1, wherein the necrosis inhibitor is a compound of Formula IV:
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22. The method of claim 1, wherein the necrosis inhibitor is a compound of Formula V:
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23. The method of claim 1, wherein the necrosis inhibitor is a compound of Formula V-A:
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24. The method of claim 1, wherein the necrosis inhibitor is a compound of Formula VII:
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25. The method of claim 1, wherein the necrosis inhibitor is a compound of Formula VIII:
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26. The method of claim 1, wherein the necrosis inhibitor is a compound of Formula IX:
Specification