UNASSIGNED: Following microbead injections into the anterior chamber of the ocular cavity of rabbits, we observed elevated histiocyte numbers and immune scores for MYLK-4/ pMLC-2, alongside a reduction in the void space within the TM. Notably, treatment was performed with 0.1% ITRI-E-(S)-4046, a compound with dual kinase inhibitor (highly specific inhibitor of ROCK1/2 and MYLK4), significantly reduced intraocular pressure (IOP; P < 0.05) and expanded the void space within the TM (P < 0.0001) compared with OHT rabbits. In clinical investigations, we utilized whole transcriptome sequencing to analyze gene expression specifically related to the TM, obtained from patients (5 early-onset and 5 late-onset) undergoing trabeculectomy.
UNASSIGNED: Our findings revealed 103 differential expression genes (DEGs) out of 265 molecules associated with the Rho family GTPase pathway, exhibiting a P value of 1.25E-10 and a z-score of -2.524. These results underscore significant differences between the early-onset and late-onset POAG and highlight the involvement of the ROCK/MYLK pathway.
UNASSIGNED: These findings underscore the critical involvement of the ROCK/MYLK pathway in both OHT-related and different onsets of POAG, providing valuable insights into the TM-related molecular mechanisms underlying the disease.
■将微珠注射入兔子眼腔前房后,我们观察到MYLK-4/pMLC-2的组织细胞数量和免疫评分升高,同时TM内的空隙空间减少。值得注意的是,用0.1%ITRI-E-(S)-4046进行治疗,该化合物具有双重激酶抑制剂(ROCK1/2和MYLK4的高特异性抑制剂),与OHT兔相比,显着降低眼压(IOP;P<0.05)并扩大TM内的空隙空间(P<0.0001)。在临床调查中,我们利用全转录组测序来分析与TM特异性相关的基因表达,从接受小梁切除术的患者(5例早发性和5例晚发性)获得。
■我们的发现揭示了与Rho家族GTPase途径相关的265个分子中的103个差异表达基因(DEGs),表现出1.25E-10的P值和-2.524的z分数。这些结果强调了早发性和晚发性POAG之间的显着差异,并强调了ROCK/MYLK途径的参与。
■这些发现强调了ROCK/MYLK通路在POAG的OHT相关和不同发病中的关键参与,为潜在的TM相关分子机制提供有价值的见解。