Project: C02

The lymphatic regulator SVEP1 in Schlemm´s canal function – a therapeutic target for glaucoma

The Schlemm’s canal (SC) controls intraocular pressure (IOP) by drainage of the aqueous humor from the eye. Increased resistance to aqueous humor outflow through this system raises IOP and causes glaucoma. IOP is the main risk factor of glaucoma development and progression. Glaucoma is a leading cause of blindness. Our understanding of the pathophysiological changes of IOP increase is scarce. Hence, there is an unmet need for new treatment options to lower IOP.

To date, it is unknown which changes in SC function cause the pathological increase in IOP. It was only recently discovered that the SC consists of a highly organized, unique hybrid vascular structure combining distinct lymphatic and blood vascular endothelial features (‘atypical lymphatic vessel’). The SC itself is covered by trabecular meshwork cells facing the anterior chamber of the eye. However, most glaucoma studies focus on the trabecular meshwork rather than the SC itself. Analysis of the newly discovered lymphatic features of the SC offers a new understanding of the pathophysiology of IOP increase and provides novel treatment options in different forms of glaucoma.

The student will analyse the role of known glaucoma risk factors in relation to SC function. Specifically the will aim to: 1) describe in detail new pre-clinical Svep1+/- and Svep1/Tie2 +/- mouse models for increased IOP, (2) assess correlated protein expression changes in normal and glaucoma human tissue, (3) decipher the mode of action of SVEP1-mediated regulation of TIE-1/-2/ANG signalling, and (4) develop a new therapeutic treatment/prevention option for glaucoma via activation of TIE1/-2 signalling in SC through providing recombinant SVEP1 protein.

Key methods: in vivo transgenic models, morphometric analysis, IF, cell culture assays, FISH, RNA and protein analysis, cell signalling methodologies; pre-clinical testing