Compositions and methods for treating eye infections and disease
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 no normal tears.
1. A method comprising determining the concentration of 90 kDa deglycanated syndecan-1 (SDC-1) in a tear sample and determining if a decreased level of 90 kDa deglycanated SDC-1 is present in the sample relative to a predetermined standard, and/or detecting the presence of 25 kDa SDC-1 in a tear sample.
2. The method of claim 1 , comprising determining the concentration of 90 kDa deglycanated SDC-1 in a tear sample and determining if a decreased level of 90 kDa deglycanated SDC-1 is present in the sample relative to a predetermined standard.
3. The method of claim 1 , comprising detecting the presence of 25 kDa SDC-1 in the tear sample.
4. The method of claim 1 , comprising determining the concentration of 90 kDa deglycanated SDC-1 in a tear sample and determining if a decreased level of 90 kDa deglycanated SDC-1 is present in the sample relative to a predetermined standard, and detecting the presence of 25 kDa SDC-1 in a tear sample obtained from a single subject.
5. The method of claim 1 , further comprising screening the tear sample for the presence of inactive lacritin-C splice variant and/or latent heparanase.
6. The method of claim 1 , comprising detecting the presence of 25 kDa SDC-1 and inactive lacritin-C splice variant in the tear sample.
7. The method of claim 1 , further comprising contacting an ocular surface of a subject from which the tear sample was collected with a pharmaceutical composition comprising a lacritin polypeptide if a decreased level of 90 kDa deglycanated SDC-1 is present in the sample relative to a predetermined standard and/or the presence of 25 kDa SDC-1 is detected in the sample.
8. The method of claim 7 , 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.