Vitreous as a Substrate for Vitreolysis

There is an increasing interest in the concept of using enzymes to induce vitreoretinal separation and/or modulate the structure of the vitreous as an aid to, or replacement for, mechanical vitrectomy. In order to understand how these enzymes work and to develop new and better therapeutics, knowledge of vitreous structure at a molecular and supramolecular level is key. The vitreous like many extracellular matrices has a composite structure with a network of collagen fibrils, that is essential for the gel structure, and a glycosaminoglycan network composed predominantly of hyaluronan that fills the spaces between the collagen fibrils and helps to inflate the matrix. The collagen fibrils are very resistant to proteolytic degradation so these do not make a good target for pharmacological vitreolysis, but degradation of the hyaluronan facilitates the dispersal of vitreous haemorrhage. The molecular mechanisms underlying postbasal vitreoretinal adhesion are poorly understood but it is likely that intermediary molecules that link cortical vitreous collagen fibrils to the inner limiting lamina play a major role. Furthermore, it is apparent that proteolytic enzymes such as plasmin fragment these linking molecules and thereby facilitate vitreoretinal disinsertion.