Effects of tetrathiomolybdate in a mouse model of retinal neovascularization.
OBJECTIVE
To determine the effects of tetrathiomolybdate (TM), a copper-chelating agent, on retinal angiogenesis and vascular endothelial growth factor (VEGF) in a mouse model of retinal neovascularization.


METHODS
Postnatal day (P)7 C57BL/6N mice were exposed to 75% +/- 2% oxygen for 5 days (P7-P11) and then returned to room air for 5 days (P12-P17) to induce retinal neovascularization. Beginning on P10 or P12, mice received daily intraperitoneal injections of TM or phosphate-buffered saline (PBS; control) through P17. Retinal neovascularization was examined by fluorescein dextran angiography after 5 days in room air and was quantitated histologically by counting the neovascular endothelial cell nuclei anterior to the inner limiting membrane. TM's effects on VEGF expression were measured by ELISA.


RESULTS
TM-treated and control animals demonstrated comparable regions of retinal nonperfusion. Retinas from control mice at P17 contained neovascular tufts at the junction between perfused and nonperfused retina. The tufts contained numerous neovascular nuclei. Retinas from mice treated with TM beginning on P10 (2 days before returning to room air), but not P12, demonstrated a 41% reduction in neovascular cell nuclei compared with control mice (P <0.01). The P10-treated mice also demonstrated a 24% reduction of VEGF compared with control animals (P=0.01).


CONCLUSIONS
TM significantly inhibits retinal neovascularization and VEGF production in a mouse model of retinal neovascularization.
Elner
Susan G
SG
Department of Ophthalmology, University of Michigan, Ann Arbor, MI 48105, USA.
Elner
Victor M
VM
Yoshida
Ayako
A
Dick
Robert D
RD
Brewer
George J
GJ
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D002614:Chelating Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005451:Fluorescein Angiography; D007274:Injections, Intraperitoneal; D007511:Ischemia / Q000150:complications; D051379:Mice; D008810:Mice, Inbred C57BL; D008982:Molybdenum / Q000627:therapeutic use*; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D002614:Chelating Agents; D042461:Vascular Endothelial Growth Factor A; D008982:Molybdenum; C020809:tetrathiomolybdate