Lack of thrombospondin 1 and exacerbation of choroidal neovascularization.
OBJECTIVE
To assess the impact of thrombospondin 1(TSP1) deficiency on choroidal neovascularization (CNV)and to determine whether administration of a TSP1 antiangiogenic mimetic peptide attenuates CNV.


METHODS
The impact of TSP1 deficiency on laser induced CNV was assessed using wild-type (TSP1 +/+) and TSP1-deficient (TSP1 −/−) mice. Three laser burns were placed in each eye of TSP1 +/+ and TSP1 −/− mice to induce CNV. Intravitreal injection of the TSP1 mimetic peptide was performed on days 1 and 7 postlaser in the mice.For quantitative measurements of neovascularization, intercellular adhesion molecule 2 staining was performed at 14 days postlaser of the choroidal-sclera flat mounts. The recruitment of macrophages to the sites of damage was investigated by immunohistochemistry. The CNV area was measured by intercellular adhesion molecule 2 staining and use of ImageJ software.


RESULTS
The TSP1 −/− mice exhibited significantly larger areas of neovascularization on choroidal flat mounts compared with TSP1 +/ mice. This was consistent with enhanced recruitment of macrophages in TSP1 −/− mice compared with TSP1 +/+ mice 3 days postlaser. The development of CNV was significantly attenuated in mice receiving the TSP1 antiangiogenic mimetic peptide compared with those receiving vehicle alone.


CONCLUSIONS
Deficiency of TSP1 contributes to enhanced choroidal neovascularization. This is consistent with the anti-inflammatory and antiangiogenic activity of TSP1. The TSP1 antiangiogenic peptide was effective in attenuation of CNV.


CONCLUSIONS
Intravitreal injection of TSP1 antiangiogenic mimetic peptides may provide alternative treatment for CNV.
Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, 600 Highland Ave, K6/456 CSC, Madison, WI 53792, USA.
Shoujian
S
Wang
Christine M
CM
Sorenson
Nader
N
Sheibani
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D032701:Biomimetics; D020256:Choroidal Neovascularization / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D058449:Intravitreal Injections; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D019700:Thrombospondin 1 / Q000172:deficiency*
D020533:Angiogenesis Inhibitors; D009842:Oligopeptides; D019700:Thrombospondin 1