Remodeling of the human vitreous body: cross-linking and enzymatic degradation of collagens

PhD ceremony: Ms. M. van Deemter, 14.45 uur, Academiegebouw, Broerstraat 5, Groningen

Thesis: Remodeling of the human vitreous body: cross-linking and enzymatic degradation of collagens

Promotor(s): prof. J.M.M. Hooymans, prof. R.A. Bank

Faculty: Medical Sciences

With aging, the vitreous body liquefies, and posterior vitreous detachment (PVD) can develop. PVD as well as persistent vitreoretinal adhesion can lead to retinal pathology, often needing surgical intervention to cure. Here, three possible mechanisms of vitreous remodeling are described.

Firstly, evidence for enzymatic degradation of vitreous type II collagen was found. Both matrix metalloproteinases and one or more trypsin-isoforms appear to be involved. These enzymes are also capable of degrading vitreoretinal adhesion proteins, and could therefore also have a role in the development of PVD.

Secondly, collagen cross-linking was studied. The enzymatic cross-linking profile suggested that collagen synthesis and maturation in the vitreous continue until the age of 50 years. After that, the number of enzymatic cross-links diminishes, consistent with the loss of structural integrity of the vitreous matrix.

Finally, the accumulation of advanced glycation endproducts (AGEs) in the vitreous is described. AGEs are known to alter tissue structure and function. AGEs were shown to accumulate with aging. Eyes with a PVD had on average lower AGE concentrations than eyes without a PVD. As AGE-accumulation has a negative effect on protein degradation, this finding is an extra indication that proteolytic enzymes are involved in the development of PVD. Furthermore, AGEs may influence the development of diseases characterized by persistent vitreoretinal adhesion.

Vitreous liquefaction and PVD are major events in aging eyes. Since both processes influence a range of ocular diseases, a better understanding of their pathogenesis could lead to the development of less invasive treatments and decrease patient discomfort.