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 administering agents that cause directly or indirectly upregulation of the ABCA1 transporter protein in macrophages. These agents include, without limitation, LXR agonists. In some embodiments, inhibitors of CETP expression or activity can also be effective. Administration routes can include, without limitation, intraocular, periocular, or systemic administration.
1. A method of treating an ocular disease characterized by choroidal neovascularization (CNV) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an inhibitor of cholesteryl ester transfer protein (CETP) activity.
2. A method in accordance with claim 1 , wherein the inhibitor of CETP activity is selected from the group consisting of ethyl (2R,4S)-4-({[3,5-bis(trifluoromethyl)phenyl]methyl}(methoxycarbonyl)amino)-2-ethyl-6-(trifluoromethyl)-1,2,3,4-tetrahydroquinoline-1-carboxylate (Torcetrapib), (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({2-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]-5-(trifluoromethyl)phenyl}methyl)-4-methyl-1,3-oxazolidin-2-one (Anacetrapib) and S-[2-({[1-(2-ethylbutyl)cyclohexyl]carbonyl}amino)phenyl]2-methylpropanethioate (Dalcetrapib).
3. A method in accordance with claim 1 , wherein the administering a therapeutically effective amount of an inhibitor of CETP activity comprises intraocularly injecting a pharmaceutically acceptable formulation comprising the inhibitor.
4. A method in accordance with claim 1 , wherein the administering a therapeutically effective amount of an inhibitor of CETP activity comprises administering to an eye of the subject a pharmaceutically acceptable eye drop formulation comprising the inhibitor.
5. A method in accordance with claim 1 , wherein the administering a therapeutically effective amount of inhibitor of CETP activity comprises administering the inhibitor orally in a pharmaceutically acceptable formulation.
6. A method in accordance with claim 1 , wherein the administering a therapeutically effective amount of inhibitor of CETP activity comprises administering the inhibitor parenterally in a pharmaceutically acceptable formulation.