Overexpression of foxc1 to treat corneal vascularization

Abstract

Disclosed are methods and pharmaceutical compositions for treating and inhibiting conical vascularization including conical vascularization associated with viral infection, chemical injury, autoimmune conditions, and post-corneal transplantation or in subjects having a PAX6 mutation associated with conical vascularization. The methods and pharmaceutical compositions are utilized in administering treatment that results in increased concentration of FOXC1 in a subject's cornea in order to treat or inhibit corneal vascularization.

We claim: 
     
         1 . A method for treating and/or inhibiting corneal vascularization in a subject in need thereof, the method comprising administering a therapeutic agent to the subject that results in an increase in concentration of FOXC1 in the cornea of the subject than the concentration of FOXC1 in the cornea of the subject prior to administering the therapeutic agent. 
     
     
         2 . The method of  claim 1 , wherein the therapeutic agent is administered to the cornea of the subject. 
     
     
         3 . The method of  claim 1 , wherein the therapeutic agent is administered to the surface of the cornea of the subject. 
     
     
         4 . The method of  claim 1 , wherein the therapeutic agent is a vector that expresses FOXC1 or a variant thereof comprising an amino acid sequence having at least about 80% sequence identity to SEQ ID NO:1. 
     
     
         5 . The method  claim 1 , wherein the therapeutic agent is a viral vector that expresses FOXC1 or a variant thereof comprising an amino acid sequence having at least about 80% sequence identity to SEQ ID NO:1. 
     
     
         6 . The method  claim 1 , wherein the therapeutic agent is an adenovirus-associated viral vector that expresses FOXC1 or a variant thereof comprising an amino acid sequence having at least about 80% sequence identity to SEQ ID NO:1. 
     
     
         7 . The method of  claim 1 , wherein the therapeutic agent is a pharmaceutical composition comprising: (i) FOXC1 or a variant thereof comprising an amino acid sequence having at least about 80% sequence identity to SEQ ID NO:1; and (ii) a carrier, excipient, or diluent. 
     
     
         8 . The method of  claim 1 , wherein the therapeutic agent is a pharmaceutical composition comprising: (i) FOXC1 or a variant thereof comprising an amino acid sequence having at least about 80% sequence identity to SEQ ID NO:1 fused to one or more cell penetrating peptides; and (ii) a carrier, excipient, or diluent. 
     
     
         9 . The method of  claim 1 , wherein the subject has or at risk for developing corneal vascularization from bacterial or viral infection, corneal vascularization from chemical injury, corneal vascularization from an autoimmune response, or conical vascularization after a conical transplant. 
     
     
         10 . The method of  claim 1 , wherein the subject has a PAX6 mutation and the subject has or is at risk for developing corneal vascularization due to the PAX6 mutation. 
     
     
         11 . A vector that is capable of expressing FOXC1 in a cornea of a subject in need thereof. 
     
     
         12 . The vector of  claim 11 , wherein the vector is capable of expressing FOXC1 or a variant thereof comprising an amino acid sequence having at least about 80% sequence identity to SEQ ID NO:1 in the cornea of the subject in need thereof. 
     
     
         13 . The vector of  claim 11 , wherein the vector is a viral vector. 
     
     
         14 . The vector of  claim 11 , wherein the vector is an adenovirus-associated viral vector. 
     
     
         15 . A pharmaceutical composition comprising: (i) FOXC1 or a variant thereof comprising an amino acid sequence having at least about 80% sequence identity to SEQ ID NO:1; and (ii) a carrier, excipient, or diluent. 
     
     
         16 . A pharmaceutical composition comprising: (i) FOXC1 or a variant thereof comprising an amino acid sequence having at least about 80% sequence identity to SEQ ID NO:1 fused to one or more cell penetrating peptides; and (ii) a carrier, excipient, or diluent. 
     
     
         17 . A method for identifying a test subject having or at risk for developing corneal vascularization, the method comprising: (i) detecting expression levels of FOXC1 in a cornea of the test subject; (ii) comparing the detecting expression levels of FOXC1 in the cornea of the test subject to expression levels of FOXC1 in a cornea of a control subject not having or at risk for developing corneal vascularization; and (iii) determining that the test subject has lower expression levels of FOXC1 in the cornea compared to expression levels of FOXC1 in the cornea of the control subject. 
     
     
         18 . The method of  claim 17 , further comprising administering a therapeutic agent to the test subject that results in increased concentration of FOXC1 in the cornea of the test subject relative to the concentration of FOXC1 in the cornea of the test subject prior to administering the therapeutic agent. 
     
     
         19 . The method of  claim 18 , wherein the therapeutic agent is administered to the cornea of the subject. 
     
     
         20 . The method of  claim 18 , wherein the therapeutic agent is a vector that expresses FOXC1 or a variant thereof comprising an amino acid sequence having at least about 80% sequence identity to SEQ ID NO:1.