Effect of Histone Deacetylase Inhibitor, Butyroyloxymethyl-Diethyl Phosphate (AN-7), on Corneal Neovascularization in a Mouse Model.
To examine whether butyroyloxymethyl-diethyl phosphate (AN-7), a histone deacetylase inhibitor, inhibits chemically induced corneal neovascularization (NV) in mice.



Corneal NV was induced in the right eye of male C57BL mice by application of a mixture of 75% silver nitrate and 25% potassium nitrate to the corneal center. Immediately thereafter, the mice were randomized into 2 groups, receiving an intraperitoneal injection of AN-7 or saline, which served as control. Corneal NV was evaluated at constant time intervals from the corneal injury by corneal photographs and the area of corneal NV was measured. Centricity and density of the corneal vascularization were graded. Corneal flat mounts blood vessels staining and histological studies were performed on day 10. Unpaired t-test was used for group comparisons.



The corneal neovascular area was statistically significantly reduced by AN-7 treatment on days 10 and 14 postinjury and compared with the untreated group. The centricity and density of the corneal NV between treated and untreated groups showed no significant difference at any time point.



Systemic treatment with AN-7 had a significant inhibitory effect on chemical burn-induced corneal NV in mice. These results suggest that AN-7 should be further evaluated for its therapeutic potential for the treatment of corneal NV.
1 Department of Ophthalmology, Rabin Medical Center , Petah Tikva, Israel .
Michal
M
Schaap-Fogler
1 Department of Ophthalmology, Rabin Medical Center , Petah Tikva, Israel .|2 Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .
Irit
I
Bahar
3 Laboratory of Experimental Pharmacology and Oncology, Felsenstein Medical Research Center , Petah Tikva, Israel .
Ada
A
Rephaeli
4 Laboratory of Eye Research, Felsenstein Medical Research Center , Petah Tikva, Israel .
Mor
M
Dahbash
5 Department of Chemistry, Bar Ilan University , Ramat Gan, Israel .
Abraham
A
Nudelman
1 Department of Ophthalmology, Rabin Medical Center , Petah Tikva, Israel .|2 Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .
Eitan
E
Livny
4 Laboratory of Eye Research, Felsenstein Medical Research Center , Petah Tikva, Israel .
Tilda
T
Barliya
4 Laboratory of Eye Research, Felsenstein Medical Research Center , Petah Tikva, Israel .
Yael
Y
Nisgav
2 Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .|4 Laboratory of Eye Research, Felsenstein Medical Research Center , Petah Tikva, Israel .
Tami
T
Livnat
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002087:Butyrates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D009943:Organophosphorus Compounds; C502471:diethoxyphosphoryloxymethyl butanoate; D006655:Histone Deacetylases
AN-7; HDAC inhibitor; butyroyloxymethyl-diethyl phosphate; corneal neovascularization