Compositions and methods for treating eye infections and disease

Abstract

The present invention provides compositions and methods for identifying subjects suffering from dry eye that can be treated by topical administration of a composition comprising lacritin or a bioactive fragment thereof. The application discloses in part that a ˜90 KDa deglycanated form of syndecan-1 is abundant in tears of normal individuals but not individuals suffering from dry eye, whereas a ˜25 kDa syndecan-1 fragment is detectable in dry, but not normal tears.

1 - 20 . (canceled) 
     
     
         21 . A method comprising determining the concentration of monomeric lacritin in the tear sample from an individual and determining if a decreased concentration of monomeric lacritin is present in the sample relative to a predetermined standard for monomeric lacritin. 
     
     
         22 . The method of  21 , wherein determining the concentration monomeric lacritin in the tear sample comprises a method selected from the group comprising an enzyme-linked immunosorbent assay (ELISA), immunoassay, immunofluorescence, immunohistochemistry, immunoprecipitation, and western blot. 
     
     
         23 . The method of  claim 21 , wherein the sample is from an individual suffering from aqueous deficient dry eye. 
     
     
         24 . The method of  claim 21 , wherein the predetermined standard for monomeric lacritin is a concentration of monomeric lacritin present in a tear sample from an individual not suffering from aqueous deficient dry eye. 
     
     
         25 . The method of  claim 21 , further comprising determining the concentration of an inactive lacritin-C splice variant, 90 kDa deglycanated syndecan-1 (SDC-1) and/or latent heparanase in the tear sample, and determining whether:
 an increased concentration of inactive lacritin-C splice variant is present in the sample relative to a predetermined standard for inactive lacritin-C splice variant;   a decreased concentration of 90 kDa deglycanated SDC-1 is present in the sample relative to a predetermined standard for 90 kDa deglycanated SDC-1; and/or   a decreased concentration of latent heparanase is present in the sample relative to a predetermined standard for latent heparanase.   
     
     
         26 . The method of  claim 21 , further comprising contacting an ocular surface of the individual with a pharmaceutical composition comprising a lacritin polypeptide when a decreased concentration of monomeric lacritin is present in the sample relative to the predetermined standard for monomeric lacritin. 
     
     
         27 . The method of  claim 21 , further comprising contacting an ocular surface of the individual with a pharmaceutical composition comprising a lacritin polypeptide when:
 a decreased concentration of monomeric lacritin is present in the sample relative to the predetermined standard,   an increased concentration of inactive lacritin-C splice variant is present in the sample relative to a predetermined standard for inactive lacritin-C splice variant;   a decreased concentration of 90 kDa deglycanated SDC-1 is present in the sample relative to a predetermined standard for 90 kDa deglycanated SDC-1; and   a decreased concentration of latent heparanase is present in the sample relative to a predetermined standard for latent heparanase.   
     
     
         28 . The method of  claim 26 , wherein the lacritin polypeptide is a polypeptide of SEQ ID NO: 1 or a bioactive fragment of lacritin selected from the group consisting of
 KQFIENGSEFAQKLLKKFS (SEQ ID NO: 5);   KQFIENGSEFAQKLLKKFSLLKPWA (SEQ ID NO: 7);   KQFIENGSEFANKLLKKFS (SEQ ID NO: 6);   KQFIENGSEFANKLLKKFSLLKPWA (SEQ ID NO: 8) and   a derivative of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 or SEQ ID NO: 8 that differs from SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 or SEQ ID NO: 8 by one, two or three amino acid substitutions, additions or deletions.   
     
     
         29 . The method of  claim 28 , wherein the lacritin polypeptide has an amino acid sequence consisting of SEQ ID NO: 5, wherein the C-terminus of the peptide is amidated, wherein the N-terminus of the peptide is acetylated.