Differential protein expression in tears of patients with primary open angle and pseudoexfoliative glaucoma

Primary open angle (POAG) and pseudoexfoliative glaucoma (PXG) are the most common
primary and secondary forms of glaucoma, respectively. Even though the patho-physiology,
aqueous humor composition, risk factors, clinical features, therapy and drug induced ocular
surface changes in POAG and PXG have been widely studied, to date information concerning
tear protein characterization is lacking. Tears are a source of nourishment for ocular surface
tissues and a vehicle to remove local waste products, metabolized drugs and inflammatory
mediators produced in several ophthalmic diseases. In glaucoma, the proteomic definition of tears
may provide insights concerning patho-physiology of the disease and ocular surface modifications
induced by topical therapy. Our study aimed at characterizing protein patterns in tears of patients
with medically controlled POAG and PXG. A comparative tears proteomic analysis by label-free
LC-MSE highlighted differences in the expression of several proteins in the two glaucoma subtypes
and control subjects, highlighting inflammation pathways expressed in both diseases.
Results were independently reconfirmed by SDS-PAGE and linear MALDI-TOF MS, validating
altered levels of Lysozyme C, Lipocalin-1, Protein S100, Immunoglobulins and Prolactin
Inducible Protein. Moreover, we found a differential pattern of phosphorylated Cystatin-S that
distinguishes the two pathologies. The most relevant results suggest that in both pathologies there
may be active inflammation pathways related to the disease and/or induced by therapy. We show,
for the first time, tear protein patterns expressed under controlled intraocular pressure conditions
in POAG and PXG subjects. These findings could help in the understanding of molecular
machinery underlying these ophthalmologic diseases, resulting in early diagnosis and more specific
therapy.