Abstract
Purpose :
Fibrosis is the common end point of chronic inflammatory conditions and involves the accumulation of extra-cellular matrix (ECM) proteins. In glaucoma, a common site for this is the lamina cribrosa of the optic nerve head (ONH). LC Fibroblast cells have been demonstrated to play an integral role in the profibrotic ECM remodelling in glaucoma. Piezo1 is a calcium-sensitive mechanosensitive ion channel, which has been demonstrated to be over-activated in a variety of systemic fibroproliferative diseases, including ocular, lung, renal and cardiac tissue. However, its effect in LC cells has not yet been investigated. Our aim is to investigate the role of Piezo1 in the fibrotic gene activation in glaucomatous lamina cribrosa cells.
Methods :
Human LC cells, obtained from age-matched “normal” and glaucomatous donors, were cultured from passage 4 and 9. Cells were grown on different substrate stiffness, 12kPa (reflecting normal physiological LC stiffness) and 100kPa (representing the “stiff” glaucomatous LC environment). Piezo1 gene transcription levels were measured using quantitative real-time RT-PCR.
Results :
The results showed there was an increased expression of Piezo1 in normal cells cultured on 100 kPa substrate stiffness, reflecting glaucomatous conditions. This result was confirmed when significant upregulation of Piezo1 was found in cultured glaucomatous LC cells.
Conclusions :
Elevated expression levels of Piezo1 were found in normal LC cells cultured in stiff conditions, and in glaucomatous LC cells. We aim to further delineate the role of Piezo1 and its downstream effects in the fibrotic pathway in glaucomatous LC cells. From this, a possible alternative therapeutic target for the definitive treatment of glaucoma may be revealed.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.