Detection of high risk drusen
In some aspects, methods of detecting complement activation in vivo, e.g., in an eye, are provided. In some embodiments, methods comprise detecting drusen containing or in close proximity to complement activation. In some embodiments methods comprise detecting one or more drusen having inflamed endothelium underlying or in close proximity thereto. In some embodiments methods comprise detecting eye-derived extracellular microvesicles, e.g., exosomes, in a body fluid. In some embodiments any of the methods further comprises treating a subject at risk of developing AMD, GA, or advanced AMD or at increased likelihood of rapid progression of AMD with a complement inhibitor. In some aspects, agents useful for performing one or more of the methods are described.
1. A method of treating a subject at risk of development or progression of age-related macular degeneration (AMD), the method comprising:
(a) providing a body fluid sample obtained from the subject;
(b) detecting an increased level of eye-derived extracellular vesicles (EVs) in the body fluid sample of the subject relative to a level of eye-derived EVs in a body fluid sample from a healthy individual not suffering from AMD; and
(c) administering a complement inhibitor to the subject based at least in part on detecting an increased level of eye-derived EVs in step (b).
2. The method of claim 1 , wherein at least some of the eye-derived EVs originate from retinal cells or retinal pigment epithelial (RPE) cells.
3. The method of claim 1 , wherein the EVs comprise at least one cell-type specific marker for RPE cells or retinal cells.
4. The method of claim 1 , wherein the EVs comprise at least one cell-type specific marker for RPE cells or retinal cells, wherein the marker is an eye-specific opsin.
5. The method of claim 1 , wherein the body fluid is blood.
6. The method of claim 1 , wherein the method comprises detecting one or more eye-specific cellular markers in or on the EVs.
7. The method of claim 1 , wherein the EVs comprise exosomes.