COMPOSITIONS AND METHODS FOR PREVENTION AND TREATMENT OF CORNEAL HAZE AND SCARRING
This application discloses ophthalmic formulations and methods for treating and preventing corneal haze and scarring with an hepatocyte growth factor (HGF) agent.
1 . A method of treating corneal scarring comprising
administering a composition comprising purified hepatocyte growth factor (HGF) polypeptide, wherein the HGF polypeptide comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 1, to a subject in need thereof, where the composition is topically administered to the cornea and the corneal scarring is reduced in severity.
2 . The method of claim 1 , wherein the HGF polypeptide comprises an amino acid sequence having at least 98% sequence identity to SEQ ID NO: 1.
3 . The method of claim 2 , wherein the HGF polypeptide comprises an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 1.
4 .- 6 . (canceled)
7 . The method of claim 1 , wherein the purified HGF polypeptide is present in a concentration of 0.001% to 1% w/v.
8 . The method of claim 1 , wherein the purified HGF polypeptide is present in a concentration of about 0.005% to 0.5% w/v.
9 . (canceled)
10 . The method of claim 1 , wherein the composition is administered daily for 5 days after an injury to the cornea.
11 . The method of claim 1 , wherein the composition is administered daily for 3 days after an injury to the cornea.
12 . The method of claim 1 , wherein the composition is administered 1 day after an injury to the cornea.
13 .- 26 . (canceled)
27 . The method of claim 1 , wherein the composition is formulated as an eye drop.
28 .- 32 . (canceled)
33 . A method of treating corneal scarring, comprising administering to a subject in need thereof a composition comprising a purified hepatocyte growth factor (HGF) polypeptide, wherein the HGF polypeptide comprises an amino acid sequence that is a fragment of the amino acid sequence of full length human HGF set forth in SEQ ID NO: 1, or a conservatively modified variant thereof; and the amino acid sequence of the HGF polypeptide has at least 85% sequence identity to SEQ ID NO:1.
34 . The method of claim 33 , wherein the amino acid sequence of the HGF polypeptide has least 90% sequence identity to SEQ ID NO: 1.
35 . The method of claim 33 , wherein the amino acid sequence of the HGF polypeptide has least 95% sequence identity to SEQ ID NO: 1.
36 . The method of claim 33 , wherein the fragment does not comprise amino acid residues 1 to 31 of SEQ ID NO: 1.
37 . The method of claim 33 , wherein the fragment does not comprise amino acid residues 1 to 31 of SEQ ID NO: 1, and the amino acid sequence of the HGF polypeptide has at least 95% sequence identity to SEQ ID NO: 1.
38 . The method of claim 36 , wherein the fragment is a conservatively modified variant of SEQ ID NO: 1 having a deletion comprising less than 1% of the amino acid residues of SEQ ID NO:1.
39 . The method of claim 33 , wherein the HGF polypeptide binds to cMET and induces signal transduction.
40 . The method of claim 33 , wherein the purified HGF polypeptide is present in a concentration of 0.001% to 1% w/v.
41 . The method of claim 33 , wherein the purified HGF polypeptide is present in a concentration of about 0.005% to 0.5% w/v.
42 . The method of claim 33 , wherein the composition is administered as an eye drop about every 24 hours, about every 12 hours, about every 6 hours, or about every 3 hours.
43 . The method of claim 42 , wherein the composition is administered for about 7 days, about 14 days, about 30 days, about 60 days, or about 90 days.
44 . The method of claim 33 , wherein the subject has an injury to the cornea.
45 . The method of claim 44 , wherein the injury is the result of a chemical burn or an industrial accident.
46 . The method of claim 33 , wherein the subject has an ocular disease.
47 . The method of claim 33 , wherein the subject has an infection of the eye.
48 . The method of claim 47 , wherein the infection is a contact lens-related infection or optical herpes.
49 . The method of claim 33 , wherein the composition is administered to the subject before or after eye surgery.
50 . The method of claim 49 , wherein the eye surgery is laser vision correction surgery.
51 . A method of treating corneal scarring comprising administering to a subject in need thereof a composition comprising a purified hepatocyte growth factor (HGF) polypeptide, wherein the HGF polypeptide is a conservatively modified variant of the amino acid sequence of full length human HGF set forth in SEQ ID NO: 1,
wherein the conservatively modified variant is a fragment that does not comprise amino acid residues 1 to 31 of SEQ ID NO: 1;
wherein the fragment comprises a deletion of less than 1% of the amino acid residues of SEQ ID NO:1;
the HGF polypeptide comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 1; and
the HGF polypeptide binds to cMET and induces signal transduction.
52 . A method of treating corneal scarring in a subject, comprising:
administering to the subject a composition comprising purified hepatocyte growth factor (HGF) polypeptide, wherein the HGF polypeptide comprises the amino acid sequences corresponding to residues 208-289, 302-384, and 388-470 of SEQ ID NO: 1, wherein the composition is topically administered to the cornea, and the HGF polypeptide binds to cMET and induces signal transduction.