Inhibition of AGTR1 attenuates cell proliferation after glaucoma filtration surgery via NF-κB pathway-mediated G0/G1-phase cell cycle arrest.

Fibroblast proliferation after glaucoma filtration surgery (GFS) plays a pivotal role in scar formation. Angiotensin type 1 receptor (AGTR1) is involved in tissue remodeling. Our previous study demonstrated that treatment with an AGTR1 blocker prolonged the survival of filtering blebs following GFS. However, whether AGTR1 participates in fibroblast proliferation after GFS remains unclear. This study examined the mechanisms underlying the involvement of AGTR1 in the activation of cell proliferation following GFS. AGTR1 expression was increased in Tenon capsule tissue of patients with glaucoma. AGTR1 inhibition resulted in a decrease in TGF-β2-induced human Tenon capsule fibroblast (HTF) proliferation and a mitigation of subconjunctival cell proliferation following GFS. Additionally, lower AGTR1 expression led to a higher percentage of HTFs in the G0/G1 phase via the p21Waf1/Cip1/Cyclin D/Cyclin E pathway. Furthermore, the addition of BAY 11-7082, a blocker of the NF-κB pathway, resulted in further inhibition of Ki67, Cyclin D, and Cyclin E expressions and an increase in the percentage of HTFs in the G0/G1 phase. In conclusion, our findings indicate that AGTR1 inhibition can attenuate HTF proliferation by leading to cell cycle arrest in the G0/G1 phase through the NF-κB pathway. Targeting AGTR1 is a feasible strategy for mitigating cell proliferation following GFS.