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Regulators of angiogenesis in the vitreous
Author(s) -
BISHOP PN,
LE GOFF MM,
TAKANOSU M,
HENRY SP,
MAYNE R
Publication year - 2008
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2008.4312.x
Subject(s) - angiogenesis , diabetic retinopathy , ophthalmology , medicine , endostatin , thrombospondin 1 , retinal , retina , chemistry , endocrinology , biology , neuroscience , diabetes mellitus
Purpose Preretinal neovascularisation is a form of angiogenesis i.e. growth of new blood vessels (into the vitreous) from the pre‐existing vessels (the retinal vasculature). The vitreous contains pro‐ and anti‐angiogenic molecules and normally the balance favours an anti‐angiogenic state. However in diseases such as proliferative diabetic retinopathy, excess pro‐angiogenic molecules, e.g. VEGF, stimulate preretinal neovascularisation. Anti‐angiogenic molecules identified in the vitreous to date include PEDF, thrombospondin‐1 and endostatin, but their relative importance in inhibiting preretinal neovascularisation remains unclear. Here we show that an endogenous glycoprotein of the vitreous called opticin has potent anti‐angiogenic properties, and provide evidence that it has a pre‐eminent role in inhibiting pre‐retinal neovascularisation. Methods Opticin null mice were generated and bred onto a C57/BL6 background. The opticin null mice and wild‐type mice +/‐ intravitreal injection with recombinant opticin (at P14) were investigated using the oxygen‐induced retinopathy model (75% oxygen from P7‐12, and analysis at P17 by serial histological sectioning). Results The opticin null mice demonstrated increased preretinal neovascular nuclei per cross section (109 +/‐ 6 S.E) compared to wild‐type controls (73 +/‐ 3) (P < 0.0001). The opticin injected wild‐type eyes showed a decrease in preretinal neovascular nuclei per cross‐section (38 +/‐ 3) compared to eyes injected with PBS alone (76 +/‐ 4) (P < 0.0001). Conclusion Opticin inhibits preretinal neovascularisation in a dose‐dependent manner. This is the first time that a knockout mouse has demonstated increased neovascularisation using this model. Opticin, or molecules derived from opticin, represent potential therapeutics.