Ocular delivery of cell permeant therapeutics for the treatment of retinal edema

Abstract

The present disclosure relates to a method for treating diabetic macular edema (DME) and/or retinal vein occlusion (RVO) comprising administering to the retina of a patient in need thereof an effective amount of a caspase-9 signaling pathway inhibitor. The caspase-9 signaling pathway inhibitor may include a peptide caspase-9 inhibitor and/or may be conjugated to a cell-penetrating peptide. The present disclosure further includes pharmaceutical compositions including a caspase-9 signaling pathway inhibitor. The disclosure further relates to the use of such compositions in a method for treating DME and/or RVO.

1 . A method for treating diabetic macular edema (DME) and/or retinal vein occlusion (RVO) comprising administering to the retina of a patient in need thereof an effective amount of a caspase-9 signaling pathway inhibitor. 
     
     
         2 . The method of  claim 1 , wherein the caspase-9 signaling pathway inhibitor comprises a peptide caspase-9 inhibitor. 
     
     
         3 . The method of  claim 2 , wherein the peptide caspase-9 inhibitor comprises XBIR3. 
     
     
         4 . The method of  claim 1 , wherein the caspase-9 signaling pathway inhibitor is conjugated to a cell-penetrating peptide. 
     
     
         5 . The method of  claim 4 , wherein the cell-penetrating peptide is selected from the group consisting of Penetratinl, transportan, pISl, Tat(48-60), pVEC, MAP, and MTS. 
     
     
         6 . The method of  claim 1 , wherein the caspase-9 signaling pathway inhibitor comprises XBIR3 and wherein the XBIR3 is conjugated to Penetratinl. 
     
     
         7 . The method of  claim 1 , wherein the effective amount treats DME and/or RVO by decreasing edema in the retina of the patient, as detected by optical coherency tomography (OCT). 
     
     
         8 . The method of  claim 1 , wherein the effective amount treats DME and/or RVO by decreasing retinal detachment of the retina of the patient. 
     
     
         9 . The method of  claim 1 , wherein administering is via eye drops. 
     
     
         10 . A pharmaceutical composition comprising an effective amount of a caspase-9 signaling pathway inhibitor and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is formulated for administration to a patient via eye drops. 
     
     
         11 . The composition of  claim 10 , wherein the caspase-9 signaling pathway inhibitor comprises a peptide caspase-9 inhibitor. 
     
     
         12 . The composition of  claim 11 , wherein the peptide caspase-9 inhibitor comprises XBIR3. 
     
     
         13 . The composition of  claim 11 , wherein the caspase-9 signaling pathway inhibitor is conjugated to a cell-penetrating peptide. 
     
     
         14 . The composition of  claim 13 , wherein the cell-penetrating peptide is selected from the group consisting of Penetratinl, transportan, pISl, Tat(48-60), pVEC, MAP, and MTS. 
     
     
         15 . The composition of  claim 10 , wherein the caspase-9 signaling pathway inhibitor comprises XBIR3 and wherein the XBIR3 is conjugated to Penetratinl. 
     
     
         16 . The composition of  claim 10 , wherein the effective amount treats DME and/or RVO in the patient by decreasing edema in a retina of the patient, as detected by optical coherency tomography (OCT). 
     
     
         17 . The composition of  claim 10 , wherein the effective amount treats DME and/or RVO by decreasing retinal detachment of the retina of the patient.