Methods for modulating macrophage proliferation in ocular disease using polyamine analogs

Abstract

Methods for modulating macrophage proliferation in an individual afflicted with or at risk for an ocular disease such as ARMD are provided. The methods employ a polyamine analog, or salt or protected derivative thereof. Macrophage proliferation has been implicated in a number of serious disorders, including ARMD. The invention also provides methods for aiding diagnosis and monitoring therapy of an ocular disease such as ARMD.

1 . A method of determining whether an individual is afflicted with, or at risk for, a macrophage-associated ocular disease comprising:
 detecting a level of activated or proliferating macrophages in a biological sample from the individual,   wherein detection of activated or proliferating macrophages at a level greater than a normal level indicates the individual is afflicted with, or is at risk for, a macrophage-associated ocular disease.   
     
     
         2 . The method of  claim 1 , wherein the disease is selected from the group consisting of macrophage-associated retinal disease, age-related macular degeneration (ARMD), vitreoretinopathy, and diabetic retinopathy. 
     
     
         3 . The method of  claim 1 , wherein the disease is non-exudative ARMD. 
     
     
         4 . The method of  claim 1 , wherein detecting the level of activated or proliferating macrophages comprises detecting the level of a biomarker for activated or proliferating macrophages. 
     
     
         5 . The method of  claim 1 , wherein detecting the level of activated or proliferating macrophages comprises detecting the level of CD14+/CD16+ expression, CD16+/PCNA+ expression, CCR2 expression, CD16+ expression, PCNA expression, or systemic Monocyte Chemoattractant Protein (MCP-1). 
     
     
         6 . A method of monitoring therapeutic treatment of a macrophage-associated ocular disease comprising:
 detecting the presence of activated or proliferating macrophages, or systemic MCP-1 in a biological sample from a subject before and after administration of a therapeutic agent,   wherein a decrease in activated or proliferating macrophages or systemic MCP-1 after administration of the therapeutic agent is indicative of a therapeutic response in the subject.   
     
     
         7 . The method of  claim 6 , wherein the therapeutic agent is selected from the group consisting of a polyamine analog, a salt of a polyamine analog, a protected derivative of a polyamine analog, MGBG, or a combination thereof. 
     
     
         8 . The method of  claim 6 , wherein the disease is selected from the group consisting of macrophage-associated retinal disease, age-related macular degeneration (ARMD), vitreoretinopathy, and diabetic retinopathy. 
     
     
         9 . The method of  claim 6 , wherein said disease is non-exudative ARMD. 
     
     
         10 . A method for determining severity of a macrophage-associated ocular disease comprising: detecting a level of activated or proliferating macrophages or systemic MCP-1 in a biological sample from a subject, wherein the level of activated or proliferating macrophages or systemic MCP-1 corresponds to severity of the macrophage-associated ocular disease in the subject. 
     
     
         11 . The method of  claim 10 , wherein detecting the level of activated or proliferating macrophages comprises detecting the level of a biomarker for activated or proliferating macrophages. 
     
     
         12 . The method of  claim 10 , wherein detecting the level of activated or proliferating macrophages comprises detecting the level of CD14+/CD16+ expression, CD16+/PCNA+ expression, CCR2 expression, CD16+ expression, or PCNA expression.