Effect of prostaglandin F2 analog treatment on proliferation and MAPK/ERK signaling in conjunctival tissues of glaucoma patients

Abstract

Aim: To compare the proliferation and activation of the MAPK/ERK signaling pathway in conjunctival cells between glaucoma patients treated with prostaglandin F2 (PGF2) analogs and those who did not receive PGF2 analog treatment. We hypothesized that PGF2 analog treatment increases both processes.
Methods: We conducted a retrospective cross-sectional study at the University Hospital of Split on conjunctival samples collected from PGF2-treated (PGF2-T) glaucoma patients (n = 6) and non-treated (PGF2-NT) patients (n = 4). Samples were stained for Ki-67 and phospho-ERK1/2 using immunofluorescence methods. We analyzed data using independent samples t-tests, with the significance threshold set at an α of 0.05 (P < 0.05).
Results: The proliferation marker Ki-67 and P-ERK1/2, a marker of MAPK/ERK activation, were expressed in both epithelial and stromal cells of the conjunctival tissues in glaucoma patients. Ki-67 expression was significantly higher in the conjunctival tissues of the PGF2-T group (mean (x̄) = 8.40%, standard deviation (SD) = 1.30%, P = 0.0007) compared to the PGF2-NT group (x̄ = 4.25%, SD = 1.04%). Similarly, P-ERK1/2 expression in conjunctival tissues was significantly higher in the PGF2-T group (x̄ = 17.29%, SD = 2.39%, P = 0.0094) compared to the PGF2-NT group (x̄ = 11.93%, SD = 2.53%).
Conclusions: Treatment with PGF2 analogs increases cellular proliferation and activates the MAPK/ERK signaling pathway in conjunctival tissues of glaucoma patients. This may help explain the adverse effects of these drugs. Future studies should investigate the role of MAPK/ERK signaling in conjunctival tissues and alternative pathways affected by PGF2 analogs, which may help improve glaucoma therapy and reduce adverse effects.