Structural macromolecules and supramolecular organisation of the vitreous gel

The vitreous gel is a transparent extracellular matrix that fills the cavit y behind the lens of the eye and is surrounded by and attached to the retin a. This gel liquefies during ageing and in 25-30% of the population the res idual gel structure eventually collapses away from the posterior retina in a process called posterior vitreous detachment. This process plays a pivota l role in a number of common blinding conditions including rhegmatogenous r etinal detachment, proliferative diabetic retinopathy and macular hole form ation. In order to understand the molecular events underlying vitreous liqu efaction and posterior vitreous detachment and to develop new therapies it is important to understand the molecular basis of normal vitreous gel struc ture and how this is altered during ageing. It has previously been establis hed that a dilute dispersion of thin (heterotypic) collagen fibrils is esse ntial to the gel structure and that age-related vitreous liquefaction is in timately related to a process whereby these collagen fibrils aggregate. Col lagen fibrils have a natural tendency to aggregate so a key question that h as to be addressed is: what normally maintains the spacing of the collagen fibrils? In mammalian vitreous a network of hyaluronan normally fills the spaces bet ween these collagen fibrils. This hyaluronan network can be removed without destroying the gel structure, so the hyaluronan is nor essential for maint aining the spacing of the collagen fibrils although it probably does increa se the mechanical resilience of the gel. The thin heterotypic collagen fibr ils have a coating of. non-covalently bound macromolecules which, along wit h the surface features of the collagen fibrils themselves, probably play a fundamental role in maintaining gel stability. They are likely to both main tain the short-range spacing of vitreous collagen fibrils and to link the f ibrils together to form a contiguous network. A collagen fibril-associated macromolecule that may contribute to the maintenance of short-range spacing is opticin, a newly discovered extracellular matrix leucine-rich repeat pr otein. In addition, surface Features of the collagen fibrils such as the ch ondroitin sulphate glycosaminoglycan chains of type IX collagen proteoglyca n may also play an important role in maintaining fibril spacing. Furthering our knowledge of these and other components related to the surface of the heterotypic collagen fibrils will allow us to make important strides in und erstanding the macromolecular organisation of this unique and fascinating t issue. In addition, it will open up new therapeutic opportunities as it wil l allow the development of therapeutic reagents that can be used to modulat e vitreous gel structure and thus treat a number of common, potentially bli nding, ocular conditions. (C) 2000 Elsevier Science Ltd. All rights reserve d.