Dissertation

Innovative strategies to clinically characterize the human tear proteome

Transplantation of labial salivary glands to the eyelids for patients with dry eye appears to give excellent results clinically.

Author: Raus, P.P.M.
Date: 04 September 2018
Links: Thesis in Leiden Repository

Transplantation of labial salivary glands to the eyelids for patients with dry eye appears to give excellent results clinically. To obtain more scientific evidence for this surgery, the human tear proteome was characterized and compared with salivary proteins. Not only the possible beneficial effects of the surgery in patients with dry eye disease were confirmed; the tear fluid proteome appears to contain a lot of additional information, possibly reflecting other ophthalmological and even non-ophthalmological pathologies. Top-down proteomics of tears is superior to the bottom-up approach because multiple molecular forms are detected as products of the same genes. Since structurally different protein forms are likely to have different bioactivities, the identification of these so called proteoforms, which is largely missed in bottom-up proteomics, is essential to understand the effect of a specific protein in relation to a disease. The combination of Schirmer strip based tear fluid sample collection, automated heat stabilization, a microfluidic chip-based capillary electrophoresis unit, and a benchtop high resolution mass spectrometer may make proteoform profiling of tears become applicable in the peripheral ophthalmic practice.