Methods for treating and diagnosing blinding eye diseases
This invention relates to, in part, methods and compositions that are useful for the diagnosis, treatment, or prevention of a blinding eye disease, including in the discovery of drugs that are efficacious against these diseases. Diseases include, for example, age related macular degeneration and reticular pseudodrusen disease, and the methods described herein include, for example, the method named delayed near infrared analysis (DNIRA).
1. A method for identifying whether a compound is useful for the treatment of a blinding eye disease, comprising:
(a) administering the compound to an animal whose eye comprises:
(i) a fluorescent compound ingested by retinal pigment epithelial (RPE) cells in the eye and indicating the presence of a blinding eye disease in the animal; wherein the fluorescent compound is indocyanine green (ICG) administered systemically to the animal, and
(ii) a RPE toxin in an amount effective to induce atrophy of RPE cells;
(b) exposing the eye to light having a wavelength of about 600 nm to about 900 nm effective to cause the fluorescent compound to fluoresce;
(c) comparing the eye's fluorescence pattern to a fluorescence pattern of an animal's eye that comprises the fluorescent compound and the toxin, but not the compound; and
(d) selecting the compound if the result of the comparison of step (c) indicates that the compound is useful for the treatment of a blinding eye disease.
2. The method of claim 1 , wherein the blinding eye disease is age-related macular degeneration (AMD) or reticular pseudodrusen (RPD).
3. The method of claim 1 , wherein the animal is a mouse, rat, zebrafish, rabbit, or non-human primate.
4. The method of claim 1 , wherein the toxin is sodium iodate.
5. The method of claim 1 , wherein the atrophy comprises necrosis which presents as patches.
6. The method of claim 1 , wherein the fluorescence occurs in RPE cells.
7. The method of claim 1 , wherein the comparing occurs at least about 24 hours after administering the test compound.
8. The method of claim 1 , wherein the comparing occurs at least about 7 days after administering the test compound.
9. The method of claim 1 , wherein the comparing occurs at least about 30 days after administering the test compound.
10. The method of claim 1 , wherein the method employs performing confocal scanning laser ophthalmoscopy (cSLO), fundus autofluorescence (FAF), delayed near infrared analysis (DNIRA), or optical coherence tomography (OCT).
11. The method of claim 1 , wherein the presence of a blinding eye disease is further indicated by patterns of FAF within patches of RPE damage or loss or outer retinal loss and the patterns are one or more of curvilinear, ribbon-like, reticular, oval, circular, scalloped, halo, and target-like lesions.
12. The method of claim 1 , wherein the presence of a blinding eye disease is further indicated by patterns of FAF within a border of patches of RPE damage or loss or outer retinal loss and the patterns are one or more of curvilinear, ribbon-like, reticular, oval, circular, scalloped, halo, and target-like lesions.
13. The method of claim 1 , wherein the presence of a blinding eye disease is further indicated by cross-sectional patterns or transverse patterns of RPE and/or outer retinal loss or mounds, triangles, peaks or spikes found in the sub-retinal space as observed with OCT.
14. The method of claim 1 , further comprising the step of observing the eye prior to administering the test compound and establishing one or more pre-administration characteristics of the eye.
15. The method of claim 1 , comprising administering the fluorescent compound prior to administering the test compound.
16. The method of claim 15 , wherein the method does not comprise administering (i) an additional amount of the fluorescent compound to the animal or (ii) a second fluorescent compound to the animal.
17. The method of claim 1 , comprising administering the toxin prior to administering the test compound.
18. The method of claim 1 , comprising administering the toxin prior to administering the fluorescent compound.
19. The method of claim 1 , further comprising administering:
(i) an additional amount of the toxin to the animal or
(ii) a second toxin to the animal.
20. The method of claim 19 , further comprising observing a reduction in the rate of formation, growth or expansion of patches of ocular tissue atrophy or patches of tissue loss.
21. The method of claim 1 , wherein the candidate compound is useful for treating, or reducing the rate of pathogenesis of a blinding eye disease.
22. The method of claim 1 , wherein the exposing occurs at least about 1 day after administering the fluorescent compound ICG.