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 modulating macrophage polarization in RPE cells in the eye of a subject in need thereof, comprising administering to said subject an effective amount of a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
each of R 1 and R 2 is independently H or a C 1 -C 6 alkyl and
R 3 is H or a C 1 -C 6 alkyl.
2. The method of claim 1 , wherein the compound of Formula I is bindarit.
3. The method of claim 1 , wherein the compound is formulated for sustained release.
4. The method of claim 1 , wherein the compound is formulated for ophthalmic administration.
5. The method of claim 1 , wherein the ophthalmic administration is intravitreal administration, intraocular administration, or effected to the ocular surface.
6. The method of claim 1 , wherein the subject is a human.
7. The method of claim 6 , wherein the human subject is afflicted with a blinding eye disease.
8. The method of claim 7 , wherein the blinding eye disease is characterized by an influx of macrophages across the subject's RPE relative to a subject not afflicted with the blinding eye disease.
9. The method of claim 1 , wherein the macrophage polarization is between M1 and M2.
10. The method of claim 9 , wherein the M1 macrophage polarization results in a macrophage-mediated inflammatory response.
11. The method of claim 10 , wherein the macrophage-mediated inflammatory response is decreased.
12. The method of claim 1 , wherein the RPE cells comprise a monolayer structure.
13. The method of claim 12 , wherein the RPE cell monolayer structure is preserved.
14. The method of claim 1 , wherein the macrophages are Iba1+.
15. The method of claim 1 , wherein the method further comprises administering an additional therapeutic agent.
16. The method of claim 15 , wherein the additional therapeutic agent is one or more of an anti-vascular endothelial growth factor (VEGF) agent, an angiotensin-converting enzyme (ACE) inhibitor, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, a renin inhibitor, a steroid, an agent that modulates autophagy, semapimod, a MIF inhibitor, a CCR2 inhibitor, CKR-2B, a 2-thioimidazole, CAS 445479-97-0, CCX140, clodronate, a clodonate-liposome preparation and gadolinium chloride.