Micrornas as new therapeutic targets for the prevention and/or treatment of retinopathy

Abstract

Methods and compositions are disclosed to identify plasma and vitreous microRNA (miRNA) signatures of diabetic retinopathy (DR), and then as diagnostic biomarkers for the onset and progression of DR.

1 . Transcriptomes of microRNA in the retina, retinal endothelial cells, and vitreous humor of mammalian eyes. 
     
     
         2 . The microRNA transcriptomes of  claim 1  in the retina selected from Tables 4 and 5 as set forth in SEQ ID NOS: 1-19 and 20-36 respectively. 
     
     
         3 . The microRNA transcriptosomes of  claim 1  in the vitreous humor of mammalian eyes, selected from Table 6 for normal eyes and Table 7 for diabetic eyes. 
     
     
         4 . A method to use microRNAs of  claim 1  as a diagnostic biomarker. 
     
     
         5 . The method of  claim 4 , wherein the microRNAs are a biomarker for diabetic retinopathy. 
     
     
         6 . The method of  claim 4 , wherein the microRNAs are a biomarker for the prediction of individualized therapy for diabetic retinopathy. 
     
     
         7 . The method of  claim 4  wherein microRNAs are obtained from the retina and from retinal endothelial cells and show differential expression as set forth in Tables 4 and 5 (SEQ ID NOS: 1-19 and 20-36, respectively). 
     
     
         8 . The method of  claim 4  wherein the microRNAs are obtained from vitreous humor and are selected from Table 6 and 7. 
     
     
         9 . The method of  claim 5 , wherein the microRNAs are obtained from vitreous humor and are selected from Table 8 (SEQ ID NOS: 37-65), or their homologues. 
     
     
         10 . A pharmaceutical composition comprising the transcriptomes of microRNA of  claim 1  or the microRNAs as shown in any of Tables 4, 5 or 8 (SEQ ID NOS: 1-19, 20-36, 37-65 respectively). 
     
     
         11 . The transcriptome of microRNA of  claim 1 , or the microRNAs selected from Tables 4 or 5 for use in the treatment of diabetes-induced retinal vascular damage, diabetic retinopathy, or a combination thereof. 
     
     
         12 . The microRNAs of  claim 11  selected for inhibition or treatment of diabetic retinoapathy, wherein miR-34a/b/c is selected to inhibit retinal neuronal and endothelial cell death, miR-146 a/b to inhibit NF-κB activation and inflammation, miR-31 to inhibit leukostatis and inflammation, miR-21 to help endothelial cell survival, let-7 to inhibit NF-κB activation, miR-17-3-p to inhibit leukostatis and miR-92 to block angiogenesis. 
     
     
         13 . A method to provide individualized treatment of diabetic retinopathy in a mammalian eye, the method comprising:
 a) determining the microRNA profile of the mammal that shows differential expression between diabetic and mammalian eyes; and   b) treating the mammal according to miRNA profile of the mammal.   
     
     
         14 . The method of  claim 13  wherein the determining is in the blood, retina, retinal epithelial cells and vitreous humor of the mammal, and wherein “determined” includes laboratory testing for microRNAs or obtaining the results of laboratory testing. 
     
     
         15 . A method to inhibit diabetes-induced retinal vascular damage and diabetic retinopathy in a diabetic mammal, the method comprising:
 a) selecting microRNAs that show differential expression between diabetic and normal mammals; and   b) administering the selected microRNAs to the retina and retinal vasculature of the mammal.   
     
     
         16 . The method of  claim 15  wherein the microRNAs inhibit NF-κB activation. 
     
     
         17 . The method of  claim 15  wherein the mammal is a human. 
     
     
         18 . The method of  claim 15  wherein the microRNAs are selected from the group consisting of miR-34a/b/c, miR-146, miR-155 (SEQ ID NO: 70), miR-31(SEQ ID NO: 93), miR-21 (SEQ ID NO: 92), let-7 (SEQ ID NOS: 71-78), miR-17-3r and miR-92. 
     
     
         19 . The method of  claim 15  wherein the microRNA is miR-31 (SEQ ID NO: 93). 
     
     
         20 . The method of  claim 15  wherein let-7 (SEQ ID NOS: 71-78) is administered to the retina and retinal vasculature of the diabetic mammal.