[The role of specific ROCK inhibitor in the prevention of experimental PVR in rabbits]

Abstract

Objective: To determine the effect of Y27632, a specific inhibitor of p160 Rho-associated coiled-coil forming protein kinase (ROCK), on experimental rabbit PVR.

Methods: Cultured rabbit retinal pigment epithelial cells were used in the experiments. The effects of Y27632 on RPE alpha-SMA (smooth muscle actin) stress fiber formation were studied by immuno-fluorescent staining. An in vitro type I collagen gel contraction assay and MTT assay were used to detect the effect of Y27632 on RPE cell contractile force and proliferation. Cultured 6 th passage rabbit RPE cells were injected intravitreally to induce the PVR model and then followed injection of 50 micromol/L of Y27632. The presence of tractional retinal detachment (TRD) was assessed to evaluate the effect of this agent in vivo. Electroretinography and histological studies were performed after intravitreal injection of Y27632 into untreated eyes to evaluate toxicity.

Results: The results showed that Y27632 disrupted SMA stress fiber formation in the cultured RPE cells and impaired contractile force generated by RPE cells (t = 16.212, P < 0.01). Development of TRD was significantly reduced (P < 0.01) with 50 micromol/L of Y27632. No obvious histological or retinal functional damage was found in the Y27632-treated group.

Conclusion: p160 ROCK specific inhibitor Y27632 decreased contractile force generated by RPE cells and attenuated PVR without significant side effect in rabbit. This reagent could be potential therapeutically method in the treatment of PVR.