H-1152对兔眼眼压及小梁组织超微结构的影响

The effect of H-1152 on IOP and trabecular meshwork structure in rabbit

目的观察H-1152对兔眼眼压以及小梁组织超微结构的影响,并探讨其作用机制。方法观察兔眼点用H-1152前后眼压变化,并用透射电镜分析兔眼小梁组织超微结构的变化。结果H-1152能明显降低兔眼眼压。局部点用10mmol/L的H-1152(50μL)后1～6h的眼压较对照组降低(P<0.05)。点药后2h下降至最低点,较处理前降低50.6%。与对照组相比,点药后1～3h眼压下降最明显。电镜下可见小梁间间隙增大,小梁组织中细胞外基质(ECM)减少。结论H-1152可有效降低兔眼眼压,其作用机制可能是通过降解小梁通道的ECM,改变小梁通道的构型,使房水排出阻力减少,眼压降低。H-1152有望成为治疗青光眼的有效药物。

Objective Glaucoma is an optic neuropathy caused by elevated intraocular pressure （IOP）. To low IOP is still the major therapeutic approach to this disease. Our study was designed to investigate the effects of Rho-kinase inhibitor,H-1152, on IOP and uhrastructure of trabecular meshwork in rabbits. Methods 50 μL of 10 mmol/L H-1152 was topically administered in the right eyes of 6 New Zealand white rabbits and the equal amount of physiology balance solution（PBS） was used at the same way in the left eyes as control. IOP was measured before and after the topical administration of H-1152 using pneumatometer. The ocular inflammatory manifestation was examined by the slim-lamp for the evaluation of adverse effects of H-1152. The morphologic change of rabbits trabecular meshwork was examined under the light and transmission electron microscopy. Results The IOP was significantly declined from 1 hour through 6 hours after application of 10 mmol/L （50 μL） H-1152, showing a statistically significant difference in comparison with control group（P 〈 0.05 ）. The maximum decrease scope of IOP was 50.6% at 2 hours after the topical administration of H-1152. Compared with the control groups, IOP reduction was the most dominant in the duration of 1 hour and 3 hours after H-1152 administration. No visible structural alteration was seen in trabecular meshwork tissue under the light microscope. However,the shortening of cells and widening of the extracellular spaces among the beams of the trabecular meshwork were displayed under the transmission electron microscopy in H-1152 group. No obvious adverse effect on eye tissue during the application duration of H-1152. Conclusion H-1152 decrease the IOP in rabbit probably by deterioration of the aetin cytoskeleton and cellular adhesions and the expansion of the intercellular spaces in the juxtacanalicular region. The result suggests that H-1152 has the potential effect of IOP control as an anti-glaucoma medication.