Inhibition of choroidal neovascularization
Methods of treatment of diseases that include or are characterized by inappropriate or pathological neovascularization are disclosed. These diseases include diseases of the eye, such as diabetic retinopathy, retinopathy of prematurity, and choroidal neovascularization which can occur in age-related macular degeneration (AMD). Disclosed methods include applying to macrophages in cell culture an agent that causes upregulation of ABCA1 transporter protein, and administering the macrophages to a subject. The agents include, without limitation, LXR agonists. Administration routes can include, without limitation, intraocular, periocular, and systemic administration.
1. A method of treating an ocular disease characterized by choroidal neovascularization (CNV) in a subject in need thereof, comprising:
providing a cell culture comprising macrophages; adding an activator of an ATP-binding cassette (ABC) transporter to the culture in an amount sufficient to stimulate ABC transporter expression and/or activity in the macrophages; and
administering the macrophages to the subject.
2. A method in accordance with claim 1 , wherein the activator is N-(2,2,2-trifluoroethyl)-N-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-benzenesulfonamide.
3. A method in accordance with claim 1 , wherein the activator is methyl-3β-hydroxy-5α,6α-epoxycholanate.
4. A method in accordance with claim 1 , wherein the activator is 2-[3-[3-[[2-chloro-3-(trifluoromethyl)phenyl]methyl-(2,2-diphenylethyl)amino]propoxy]phenyl]acetic acid.
5. A method in accordance with claim 1 , wherein the providing a cell culture comprising macrophages comprises providing a cell culture comprising peripheral blood mononuclear cells (PBMCs).
6. A method in accordance with claim 3 , wherein the cell culture comprising peripheral blood mononuclear cells (PBMCs) comprises PBMCs autologous to the subject.
7. A method in accordance with claim 3 , wherein the providing a cell culture comprising macrophages comprises growing macrophages comprised by the culture.
8. A method in accordance with claim 1 , wherein the administering the macrophages to the subject can comprise administering the macrophages to the subject intravenously.
9. A method in accordance with claim 1 , wherein the administering the macrophages to the subject can comprise administering the macrophages to the subject periocularly.
10. A method in accordance with claim 1 , wherein the administering the macrophages to the subject comprises administering the macrophages to the subject intraocularly.