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Shedding light on a new eye protein
  1. J V Forrester
  1. Correspondence to: J V Forrester University of Aberdeen, UK; j.forresterabdn.ac.uk

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Opticin is a proteoglycan of the small leucine rich repeat family located in the extracellular matrix

It is reassuring to realise that there are still new molecules to be discovered using classic biochemical methods rather than the blockbuster genomic approach. Opticin is an eye specific molecule discovered by Reardon and colleagues in 20001 using a 4 M guanidine hydrochloride extract from bovine vitreous collagen fibrils to prepare peptides as a starting point for molecular cloning. Almost simultaneously, a separate group of researchers discovered an iris specific molecule which they termed oculoglycan2 and was later found to be identical with opticin. In this issue of the BJO (p 697), Ramesh et al describe more fully the distribution of opticin in the human eye. Opticin was found to be present in significant quantities in several ocular tissues, particularly the ciliary body, the iris, and the anterior vitreous close to the pars plana. It is a proteoglycan of the small leucine rich repeat (LRR) family located in the extracellular matrix.

The role of opticin is not clear. In the vitreous gel, Bishop has suggested a function in maintaining gel stability and structure.3 The vitreous body is a virtually acellular connective tissue with a high content of water, and composed predominantly of a type II collagen scaffold filled with a matrix of hyaluronan. Several other collagens are also present in smaller quantities such as V/XI, VI, and IX, which act either as crosslinking proteins or directly as proteoglycans, binding together the structural but thin type II collagen fibrils with the hyaluronan filler via other proteoglycan associated glycosaminoglycans (GAGs). Other non-collagenous proteoglycans and proteins such as versican and fibulin may also be involved in stabilisation of this delicate structural lattice (for review see Bishop3).

In fact, although non-collagenous proteins form a very small percentage of the total molecular composition of the vitreous gel they are believed to have important structural roles. In addition to versican and fibulin mentioned already, fibrillin containing microfibrils are an important component although without their usual partner elastin. Other minor proteins are present instead such as microfibril associated glycoprotein-1 (MAGP-1). Opticin is present in significant amounts in vitreous and it is surprising that it has not been identified previously. It binds to heterotypic vitreous collagen fibrils and appears to be the only member of the LRR family of proteins present in the vitreous. One of the proposed functions of this family of proteins is the prevention of lateral association, or aggregation, of collagen fibrils, and its abundance in the vitreous may be relevant to the determination of appropriate short range spacing of the thin collagen fibrils of the vitreous required to permit light transmission. In this sense then, these proteins are regulators of supramolecular organisation of tissues and include other well known proteins such as decorin and lumican. These have relevance to spacing of other critical collagenous matrices such as the corneal stroma (lumican knockout mice have opaque corneas) and skin matrix. Opticin is unusual in that it is substituted with a preponderance of O-sialylated oligosaccharides instead of GAG disaccharide chains, thereby reducing the level of GAG heterogeneity in the vitreous.

Matrix molecules such as opticin may have a role in ensuring a sufficient supply of growth hormone for ocular vasculogenesis

Coating of vitreous collagen fibrils with molecules such as opticin and type IX collagen through its chondroitin sulphate chains may thus have a dual purpose: on the one hand they permit structural integrity of the vitreous gel by providing linkage to form a contiguous collagen network; on the other hand, these molecules also might prevent aggregation of the vitreous fibrils which would destabilise the gel. During ageing or disease, particularly after cellular infiltration of the gel, these molecules are likely to be damaged or degraded and thus lead to collagen fibril aggregation, lacunae formation, and gel condensation, clinically known as vitreous syneresis.

Most recently a further role for opticin has been suggested—namely, as a repository for growth factors.4 Binding of growth factors by matrix molecules is well recognised. For instance, vitreous type II collagen binds TGF-β and BMP-2.5,6 Fibroblast growth factor among many other factors is stored extracellularly in basement membranes bound to a heparan sulphate proteoglycan (syndecan).7 Now opticin appears to bind growth hormone.4 Growth hormone has been implicated in new vessel growth both directly and through its mediator insulin-like growth factor 1 (IGF-1), particularly during development, and matrix molecules such as opticin may have a role in ensuring a sufficient supply of growth hormone for ocular vasculogenesis. This may also apply to the retina and other ocular tissues since opticin appears to be widely distributed in the eye. Thus, it may have more functions besides promoting the development of the hyaloid vascular system during embryogenesis.

It is likely that further molecular functions for opticin will emerge. Opticin appears to be restricted to the eye and as such may come under the umbrella of sequestered ocular antigens and participate in immune privilege. It may thus also act as an autoantigen and induce immune mediated inflammation such as vitritis or pars planitis. So far there is no evidence for such a role but it seems attractive as a candidate autoantigen for disorders whose pathogenesis at present remains obscure.

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Opticin is a proteoglycan of the small leucine rich repeat family located in the extracellular matrix

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