Method of enhancing delivery of therapeutic compounds to the eye

1. A method of enhancing the delivery of a therapeutic agent to an eye of a subject comprising administering, by intravitreous injection, a plasmin or derivative thereof and the therapeutic agent to the eye, wherein the therapeutic agent comprises a nucleic acid expression vector.

2. The method of claim 1 , wherein the plasmin or derivative thereof is a miniplasmin or a microplasmin (ocriplasmin).

3. The method of claim 1 , wherein nucleic acid expression vector is a viral vector comprising a transgene.

4. The method of claim 3 , wherein the transgene is an opsin.

5. The method of claim 4 , wherein the opsin is selected from the group consisting of channelrhodopsin, halorhodopsin, melanopsin, pineal opsin, bacteriorhodopsin, and proteorhodopsin, or a functional variant thereof.

6. The method of claim 3 , wherein said transgene is operably linked to a cell-specific promoter.

7. The method of any one of the preceding claims, wherein the therapeutic agent is encapsulated in a nanoparticle, a polymer, or a liposome.

8. The method of claim 1 , wherein the subject is suffering from an ocular disease or disorder.

9. The method of claim 1 , wherein the plasmin or derivative thereof and the therapeutic agent are delivered concurrently or sequentially.

10. The method of claim 1 , wherein the therapeutic agent is delivered to a retinal cell.

11. The method of claim 10 , wherein the retinal cell is a retinal ganglion cell, a retinal bipolar cell, a retinal horizontal cell, an amacrine cell, a photoreceptor cell, a Müller glial cell, or a retinal pigment epithelial cell.

12. A method of increasing light sensitivity or improving or restoring vision in a subject comprising administering a plasmin or derivative thereof and a nucleic acid expression vector that encodes an opsin to the vitreous of the eye.

13. The method of claim 12 , wherein said opsin is selected from the group consisting of channelrhodopsin, halorhodopsin, melanopsin, pineal opsin, bacteriorhodopsin, and proteorhodopsin, or a functional variant thereof.

14. The method of claim 12 or 13 , wherein the subject has an ocular disease or disorder.

15. The method of claim 12 , wherein the plasmin or derivative thereof is a miniplasmin or a microplasmin (ocriplasmin).

16. The method of claim 12 , wherein said opsin is operably linked to a cell-specific promoter.

17. The method of claim 12 , wherein the plasmin or derivative thereof and the nucleic acid expression vector are delivered concurrently or sequentially.

18. The method of claim 12 , wherein the nucleic acid expression vector is delivered to a retinal cell.

19. The method of claim 18 , wherein the retinal cell is a retinal ganglion cell, a retinal bipolar cell, a retinal horizontal cell, an amacrine cell, a photoreceptor cell, a Müller glial cell, or a retinal pigment epithelial cell.

20. The method of claim 12 , wherein the nucleic acid expression vector is a viral vector.