Brockmann Claudia, Corkhill Caitlin, Jaroslawska Elzbieta, Dege Sabrina, Brockmann Tobias, Kociok Norbert, Joussen Antonia M
Corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Department of Ophthalmology, Charité - Universitätsmedizin Berlin, Augustenburger Platz, 113353, Berlin, Germany.
Berlin Institute of Health (BIH), Berlin, Germany.
Graefes Arch Clin Exp Ophthalmol. 2019 Aug;257(8):1699-1708. doi: 10.1007/s00417-019-04365-4. Epub 2019 May 31.
To investigate the influence of the selective Rho-kinase (ROCK) inhibitor, fasudil, on the mRNA level of proinflammatory factors and the retinal vascular development in mice with oxygen-induced retinopathy (OIR).
C57BL/6J mice underwent standard protocol for OIR induction from postnatal days 7 to 12. Subsequently, they received a daily intraperitoneal injection of fasudil or sodium chloride from P12 to P16. Analyses were performed using vascular staining on retinal flat mounts, RNA expression by qPCR, and immunohistochemistry on paraffin sections.
On retinal flat mounts, the proportion of avascular area and tuft formation did not differ between the fasudil and NaCl group. Immunohistochemical staining revealed a less intense staining with inflammatory markers after fasudil. Nevertheless, there were no differences on RNA level between the two groups.
In conclusion, our findings support that daily systemic application of fasudil does not decrease retinal neovascularization in rodents with oxygen-induced retinopathy. The results of our study together with the controversial results on the effects of different ROCK inhibitors from the literature makes it apparent that effects of ROCK inhibition are more complex, and further studies are necessary to analyze its potential therapeutic effects.
研究选择性Rho激酶（ROCK）抑制剂法舒地尔对氧诱导视网膜病变（OIR）小鼠促炎因子mRNA水平及视网膜血管发育的影响。
C57BL/6J小鼠在出生后第7天至第12天接受OIR诱导的标准方案。随后，从出生后第12天至第16天，它们每天接受腹腔注射法舒地尔或氯化钠。使用视网膜铺片上的血管染色、qPCR检测RNA表达以及石蜡切片上的免疫组织化学进行分析。
在视网膜铺片上，法舒地尔组和氯化钠组的无血管区比例和丛状形成无差异。免疫组织化学染色显示法舒地尔处理后炎症标志物染色强度较低。然而，两组之间的RNA水平没有差异。
总之，我们的研究结果支持，每日全身应用法舒地尔不会减少氧诱导视网膜病变啮齿动物的视网膜新生血管形成。我们的研究结果与文献中关于不同ROCK抑制剂作用的有争议结果一起表明，ROCK抑制的作用更为复杂，需要进一步研究来分析其潜在的治疗效果。
