Ocular detection of amyloid proteins
Described are methods for the detection, in the eye of an individual, of protein aggregates or other misfolded proteins associated with disease using peptide or peptide mimic probes that preferentially associate with the protein aggregates or misfolded proteins, which can be accomplished non-invasively.
1. A method for detecting Aβ protein aggregates in the eye of an individual, comprising:
(A) administering to the individual a peptide probe that consists of from 10 to 50 amino acid residues and comprises an amino acid sequence that is at least 60% identical to SEQ ID NO:1, wherein said probe binds to Aβ protein aggregates and
(B) detecting probe associated with any Aβ protein aggregates present in the eye.
2. The method of claim 1 , wherein said probe is labeled with a detectable label.
3. The method of claim 2 , wherein said probe is labeled at separate sites with a first detectable label and a second detectable label, and wherein said labels generate a signal when said probe binds to said Aβ protein aggregates.
4. The method of claim 3 , wherein said first and second labels comprise pyrene.
5. The method of claim 1 , wherein said probe comprises an amino acid sequence that is at least 85% identical to SEQ ID NO:1.
6. The method of claim 1 , wherein the probe comprises an amino acid sequence selected from the group consisting of SEQ ID NO:56 and SEQ ID NO:62.
7. The method of claim 1 , wherein said administering is by systemic injection, direct injection, contacting the probe with the conjunctiva or cornea of the eye, intranasal administration or inhalation administration.
8. The method of claim 1 , wherein said probe binds to Aβ protein aggregates localized in a region of the eye selected from the group consisting of the optic nerve and the retina.
9. The method of claim 1 , wherein said Aβ protein aggregates are detected in a region of the eye selected from the group consisting of the optic nerve, lens, ciliary body, vitreous body, the retina and ocular blood vessels.
10. The method of claim 1 , wherein said detecting is conducted using a retinal imaging device, a fundus camera, a slit-lamp operated with a fluoroscopic device, or by direct inspection using regular or laser light.
11. The method of claim 1 , wherein said Aβ protein aggregates are associated with an amyloidogenic disease selected from the group consisting of Alzheimer's Disease and adult macular degeneration.
12. The method of claim 11 , wherein the adult macular degeneration is a wet or dry variant.
13. A method for detecting Aβ protein aggregates in the eye of an individual, comprising:
(A) administering to the individual a peptide probe that consists of from 10 to 50 amino acid residues and comprises an amino acid sequence that is at least 60% identical to SEQ ID NO:1, wherein said probe (i) binds to Aβ protein aggregates and (ii) generates a detectable signal when said probe binds to said Aβ protein aggregates; and
(B) detecting any detectable signal resulting from said probe binding to any protein aggregates present in the eye, wherein the presence of a detectable signal indicates the presence of a condition selected from Alzheimer's Disease, age related macular degeneration, diabetes, scrapie, BSE, CJD, chronic wasting disease (CWD) and transmissible spongiform encephalopathies (TSEs).