Opticin Therapeutics

Background


The Opticin protein was discovered and patented by Prof. Paul Bishop and colleagues at the University of Manchester in the UK.  Prof Bishop has published extensively on his research in peer reviewed journals.



Opticin


Opticin is an extracellular matrix glycoprotein and a class III member of the small leucine-rich repeat proteoglycan/protein family.  It exists as a stable 90kDa homodimer in solution and was originally identified in the vitreous humour of the eye where is bound to the surface of collagen fibrils.  Opticin is secreted by the non-pigmented ciliary epithelium and, unusually for an extracellular matrix protein, is highly expressed in adult life.



The Role of Opticin in Vasoproliferative Eye Disease


Experiments with opticin knockout mice demonstrated that whilst a lack of opticin does not affect ocular vascular development, it does make the eye susceptible to neovascular disease.  Using the oxygen-induced retinopathy model, it was shown that in the absence of opticin there was significantly more preretinal neovascularization in knockout vs. wild-type mice.  Furthermore, when excess Opticin was injected into the vitreous of wild-type mice, there was an inhibition of preretinal neovascularization compared with mice injected with carrier buffer alone. Therefore, Opticin inhibits the growth of pathological blood vessels in the vitreous in a dose-dependent manner and has the potential to treat conditions including proliferative diabetic retinopathy and retinopathy of prematurity.

Further research has shown how Opticin suppresses angiogenesis. It achieves this by inhibiting integrin-mediated vascular endothelial cell binding to extracellular matrix components including collagen.  It binds very strongly to vitreous collagen and is therefore expected to have a long half-life in the vitreous cavity.  Other potential advantages compared to current ocular anti-angiogenic therapeutics are that it inhibits angiogenesis stimulated by a variety of different growth factors rather than targeting a specific growth factor signaling pathway, and that it may have an anti-fibrotic effect.

Links to key publications:

​http://www.jbc.org/content/287/33/28027.long

http://iovs.arvojournals.org/article.aspx?articleid=2126835

http://www.jbc.org/content/278/46/45280.long

http://www.jbc.org/content/275/3/2123.long