Angiogenesis plays a key role in ocular development and disease. Opticin is an extracellular matrix small leucine-rich repeat glycoprotein which was first isolated from vitreous humour of the eye. As it is highly expressed in the eye throughout life, we hypothesised that it may contribute towards the angiogenic process. The effect of opticin on FGF-2-stimulated angiogenesis was determined using assays for monolayer wound recovery and boyden chamber (migration), tube-like structure formation and invasion in matrigel or collagen gel, and examination of protein phosphorylation using Kinexus Western arrays (Bioinformatics, Canada). The presence of opticin decreased cell migration (31%, p< 0.005), tube like structure formation (37%, p<0.001) and cell invasion (45%, p<0.001). Opticin also significantly decreased the development of blood vessel formation in the chick chorioallantoic membrane assay. Opticin decreased FGF-2-induced phosphorylation of MEK1/2 (MAPK kinase), JNK and p38 (MAPK). A decrease of MAPKs phosphorylation is known to play crucial roles in cell migration and tubular morphogenesis. Therefore, opticin maybe an inhibitor of vascular ingression into the vitreous humour.

Angiogenesis plays a key role in ocular development and disease. Normally following regression of the hyaloid vascular system the vitreous humour is avascular and anti-angiogenic. However, in diseases such as proliferative diabetic retinopathy, new blood vessels grow from the retina into the vitreous humour potentially leading to blindness. Opticin is a glycoprotein that was first isolated from vitreous humour of the eye and is a member of the extracellular matrix small leucine-rich repeat proteoglycan/protein family. As it is highly expressed in the eye throughout life we hypothesised that it contributes towards the anti-angiogenic properties of the vitreous humour. Purified recombinant opticin was generated as previously described (Le Goff et al. JBC 2003, 278:45280). Using the recombinant opticin we show that opticin potently inhibits VEGF and FGF-2-induced human retinal endothelial cell and bovine aortic endothelial cell proliferation, migration, formation of tube-like structures in matrigel and collagen, and invasion. In vivo studies showed that opticin significantly decreased FGF-2 and VEGF induced angiogenesis in chick chorioallantoic membrane assays. We also demonstrate that opticin decreases signalling through ERK1/2. These observations suggest that opticin is a key regulator of angiogenesis in the eye and further studies will elucidate its mechanisms of action.