Thematic Institutional Excellence Programme(TKP2021-EGA-24) Támogató: Emberi Erőforrások
Minisztériuma
Primary open-angle glaucoma remains a global issue, lacking a definitive treatment.
Increased intraocular pressure (IOP) is considered the primary risk factor of the
disease and it can be caused by fibrotic-like changes in the trabecular meshwork (TM)
such as increased tissue stiffness and outflow resistance. Previously, we demonstrated
that the sigma-1 receptor (S1R) agonist fluvoxamine (FLU) has anti-fibrotic properties
in the kidney and lung. In this study, the localization of the S1R in TM cells was
determined, and the anti-fibrotic efficacy of FLU was examined in both mouse and human
TM cells. Treatment with FLU reduced the F-actin rearrangement, inhibited cell proliferation
and migration induced by the platelet-derived growth factor and decreased the levels
of fibrotic proteins. The protective role of the S1R in fibrosis was confirmed by
a more pronounced increase in alpha smooth muscle actin and F-actin bundle and clump
formation in primary mouse S1R knockout TM cells. Furthermore, FLU demonstrated its
protective effects by increasing the production of nitric oxide and facilitating the
degradation of the extracellular matrix through the elevation of cathepsin K. These
findings suggest that the S1R could be a novel target for the development of anti-fibrotic
drugs and offer a new therapeutic approach for glaucoma.
