RUNX1 inhibition for treatment of proliferative vitreoretinopathy and conditions associated with epithelial to mesenchymal transition

1. A method for preventing or reducing proliferation or migration of retinal pigment epithelial (RPE) cells in a subject who has not been diagnosed with aberrant angiogenesis or small vessel disease and who comprises a retinal hole or retinal tear, the method comprising administering to the subject a composition comprising a small molecule selected from the group consisting of:

a small molecule comprising the structure of Formula I:

or a pharmaceutically acceptable salt or ester thereof, wherein

each R 1 is individually selected from halogen, alkyl, aryl, heteroaryl, or alkoxy,

and R 1 is selected from aryl or heteroaryl, and

a is 0 to 4; or

a small molecule comprising the structure of Formula III:

or a pharmaceutically acceptable salt or ester thereof, wherein

each R 1 is individually selected from halogen, alkyl, aryl, heteroaryl, or alkoxy,

R 2 is selected from aryl or heteroaryl;

R 3 is alkyl or aryl, and

a is 0 to 4; or

a small molecule comprising the structure of Formula V:

or a pharmaceutically acceptable salt or ester thereof, wherein

R 1 is H 3 , NH 2 , or NHC(O)CH 3 , and

X is CH 2 or C(O).

2. The method of claim 1 , wherein the small molecule is Ro5-3335.

3. The method of claim 1 , wherein the small molecule is Ro24-7429.

4. The method of claim 1 , wherein the small molecule is lenalidomide.

5. The method of claim 1 , wherein the small molecule decreases the expression and/or activity of RUNX1.

6. The method of claim 1 , wherein the composition further comprises methotrexate.

7. The method of claim 1 , wherein the composition further comprises an anti-inflammatory agent.

8. The method of claim 7 , wherein the anti-inflammatory agent comprises a steroid or a nonsteroidal anti-inflammatory drug (NSAID).

9. The method of claim 1 , wherein the composition is administered topically or by intravitreal injection.

10. The method of claim 1 , wherein the subject is a human.

11. The method of claim 1 , wherein the subject has not undergone surgery.

12. The method of claim 1 , wherein the inhibitor is administered prior to a surgery, during a surgery or after a surgery.

13. The method of claim 12 , wherein the surgery comprises retinal detachment surgery.

14. The method of claim 1 , wherein the subject has suffered a trauma to the eye.

15. The method of claim 1 , wherein the composition comprises a carrier or excipient suitable for administration to ocular tissue.

16. A method for preventing or reducing proliferation or migration of retinal pigment epithelial (RPE) cells in a subject who has not been diagnosed with aberrant angiogenesis or small vessel disease and who comprises a retinal hole or retinal tear, the method comprising administering to the subject a composition comprising an RNA encoding the dominant negative CBF-Beta protein CBFB-MYH11.

17. The method of claim 16 , wherein the RNA encoding the dominant negative CBF-Beta protein CBFB-MYH11 decreases the expression and/or activity of RUNX1.

18. The method of claim 16 , wherein the composition further comprises methotrexate.

19. The method of claim 16 , wherein the composition further comprises an anti-inflammatory agent.

20. The method of claim 19 , wherein the anti-inflammatory agent comprises a steroid or a nonsteroidal anti-inflammatory drug (NSAID).

21. The method of claim 16 , wherein the composition is administered topically or by intravitreal injection.

22. The method of claim 16 , wherein the subject is a human.

23. The method of claim 16 , wherein the subject has not undergone surgery.

24. The method of claim 16 , wherein the inhibitor is administered prior to a surgery, during a surgery or after a surgery.

25. The method of claim 24 , wherein the surgery comprises retinal detachment surgery.

26. The method of claim 16 , wherein the subject has suffered a trauma to the eye.

27. The method of claim 16 , wherein the composition comprises a carrier or excipient suitable for administration to ocular tissue.

28. A method for treating or reducing the severity of PVR in a subject, said method comprising:

(a) identifying a subject comprising PVR, and

(b) administering to said subject a small molecule selected from the group consisting of:

a small molecule comprising the structure of Formula I:

or a pharmaceutically acceptable salt or ester thereof, wherein

each R 1 is individually selected from halogen, alkyl, aryl, heteroaryl, or alkoxy,

and R 2 is selected from aryl or heteroaryl, and

a is 0 to 4; or

a small molecule comprising the structure of Formula III:

or a pharmaceutically acceptable salt or ester thereof, wherein

each R 1 is individually selected from halogen, alkyl, aryl, heteroaryl, or alkoxy,

R 2 is selected from aryl or heteroaryl;

R 3 is alkyl or aryl, and

a is 0 to 4; or

a small molecule comprising the structure of Formula V:

or a pharmaceutically acceptable salt or ester thereof, wherein

R 1 is H 3 , NH 2 , or NHC(O)CH 3 , and

X is CH 2 or C(O).

29. A method for treating or reducing the severity of PVR in a subject, said method comprising:

(a) identifying a subject comprising PVR, and

(b) administering to said subject an RNA encoding the dominant negative CBF-Beta protein CBFB-MYH11.

30. A method of reducing proliferation and migration of cells undergoing epithelial to mesenchymal transition (EMT) within an eye in a subject or treating or preventing an EMT related disease, comprising administrating to the subject a small molecule selected from the group consisting of:

a small molecule comprising the structure of Formula I:

or a pharmaceutically acceptable salt or ester thereof, wherein

each R 1 is individually selected from halogen, alkyl, aryl, heteroaryl, or alkoxy,

and R 2 is selected from aryl or heteroaryl, and

a is 0 to 4; or

a small molecule comprising the structure of Formula III:

or a pharmaceutically acceptable salt or ester thereof, wherein

each R 1 is individually selected from halogen, alkyl, aryl, heteroaryl, or alkoxy,

R 2 is selected from aryl or heteroaryl;

R 3 is alkyl or aryl, and

a is 0 to 4; or

a small molecule comprising the structure of Formula V:

or a pharmaceutically acceptable salt or ester thereof, wherein

R 1 is H, NH 2 , or NHC(O)CH 3 , and

X is CH 2 or C(O),

wherein the EMT related disease comprises pathologic ocular fibrosis-associated proliferation, conjunctival fibrosis, ocular cicatricial pemphigoid, corneal scarring, corneal epithelial down growth, or aberrant post-surgical fibrosis,

wherein said inhibitor is administered during or after intraocular surgery.

31. A method of reducing proliferation and migration of cells undergoing epithelial to mesenchymal transition (EMT) within an eye in a subject or treating or preventing an EMT related disease, comprising administrating to the subject a small molecule selected from the group consisting of:

a small molecule comprising the structure of Formula I:

or a pharmaceutically acceptable salt or ester thereof, wherein

each R 1 is individually selected from halogen, alkyl, aryl, heteroaryl, or alkoxy,

and R 2 is selected from aryl or heteroaryl, and

a is 0 to 4; or

a small molecule comprising the structure of Formula III:

or a pharmaceutically acceptable salt or ester thereof, wherein

each R 1 is individually selected from halogen, alkyl, aryl, heteroaryl, or alkoxy,

R 2 is selected from aryl or heteroaryl;

R 3 is alkyl or aryl, and

a is 0 to 4; or

a small molecule comprising the structure of Formula V:

or a pharmaceutically acceptable salt or ester thereof, wherein

R 1 is H 3 , NH 2 , or NHC(O)CH 3 , and

X is CH 2 or C(O),

wherein the EMT related disease comprises pathologic ocular fibrosis-associated proliferation, conjunctival fibrosis, ocular cicatricial pemphigoid, corneal scarring, corneal epithelial down growth, or aberrant post-surgical fibrosis,

wherein said inhibitor is administered during or after glaucoma surgery, cataract surgery, or Laser-Assisted In Situ Keratomileusis (LASIK).

32. A method of reducing proliferation and migration of cells undergoing epithelial to mesenchymal transition (EMT) within an eye in a subject or treating or preventing an EMT related disease, comprising administrating to the subject a an RNA encoding the dominant negative CBF-Beta protein CBFB-MYH11, wherein the EMT related disease comprises pathologic ocular fibrosis-associated proliferation, conjunctival fibrosis, ocular cicatricial pemphigoid, corneal scarring, corneal epithelial down growth, or aberrant post-surgical fibrosis, wherein said inhibitor is administered during or after intraocular surgery.

33. A method of reducing proliferation and migration of cells undergoing epithelial to mesenchymal transition (EMT) within an eye in a subject or treating or preventing an EMT related disease, comprising administrating to the subject a an RNA encoding the dominant negative CBF-Beta protein CBFB-MYH11, wherein the EMT related disease comprises pathologic ocular fibrosis-associated proliferation, conjunctival fibrosis, ocular cicatricial pemphigoid, corneal scarring, corneal epithelial down growth, or aberrant post-surgical fibrosis, wherein said inhibitor is administered during or after glaucoma surgery, cataract surgery, or Laser-Assisted In Situ Keratomileusis (LASIK).