Abstract
PurposeIt is assumed that the non-pigmented ciliary epithelium plays a role in regulating intraocular pressure via its neuroendocrine activities. To test this hypothesis, we investigated the effect on a human trabecular meshwork (TM) cell line (NTM) of co-culture with a human non-pigmented ciliary epithelium cell line (ODM-2).MethodsThe cellular cross-talk between ODM-2 and NTM cells was studied in a co-culture system in which the two cell types were co-cultured for 5 to 60min or 2, 4 and 8h and then removed from the co-culture and analyzed. Analyses of the ERK and p38 mitogen-activated protein kinase (MAPK) pathways and of the activity of TM phosphatases and matrix metalloproteins (MMPs) were performed. Acid and alkaline phosphatase activity was determined by the DiFMUP (6, 8-difluoro-4-methylumbelliferyl phosphate) assay. MMP levels were determined by gelatin zymography.ResultsExposure of NTM cells to ODM-2 cells led to the activation of the MAPK signal transduction pathways in NTM cells within 5min of co-culture. Phosphorylation of ERK1/ERK2 and p38 peaked at 10 and 15min and then decreased over time. Interaction between ODM-2 and NTM cells promoted the expression of MMP-9 in the NTM cells after 4h of co-culture.ConclusionsOur findings provide support for the hypothesis that crosstalk does indeed take place between ODM-2 and NTM cells. Future studies should be designed to determine the relationship between the MMP system, MAPK kinases and phosphatases. Manipulation of these signaling molecules and the related NTM signal transduction pathways may provide targets for developing improved treatments for glaucoma.
Highlights
According to the prediction of a general increase in age-related diseases in the coming years, it is expected that the number of glaucoma patients worldwide will reach 80 million by 2020, despite current advances in therapy [1]
mitogen-activated protein kinase (MAPK) To evaluate the cross-talk between the ciliary epithelium and the trabecular meshwork (TM), the two cell lines were co-cultured in Petri dishes
A coculture of normal trabecular meshwork (NTM) cells grown on cover slips introduced to NTM cells was used as control
Summary
According to the prediction of a general increase in age-related diseases in the coming years, it is expected that the number of glaucoma patients worldwide will reach 80 million by 2020, despite current advances in therapy [1]. While IOP management is the only effective glaucoma treatment, it cannot always prevent ongoing nerve damage, and it is still unclear which aspect of IOP (mean, peak, or diurnal) is the factor most relevant to the disease progression. The Rho-associated kinase (ROCK) inhibitors that are currently in clinical trials [8] actby relaxing the TM through inhibition of the actin cytoskeleton contractile tone of smooth muscle. This relaxation results in increased aqueous outflow directly through the TM, resulting in a lowering of the IOP [9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
