Inhibition of Retinal Ganglion Cell Loss By a Novel ROCK Inhibitor (E212) in Ischemic Optic Nerve Injury Via Antioxidative and Anti-Inflammatory Actions
| Autor: | Ching-Wen Huang, Chrong-Shiong Hwang, Chih-Peng Liu, Yi-Hsun Chen, Chih-Hung Chen, Yu-Chieh Ho, Ta-Ching Chen, Yao-Tseng Wen, Rong-Kung Tsai, Chia-Mu Tu, Keh-Liang Lin, Wan-Ru Chen |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Retinal Ganglion Cells blood-retinal barrier genetic structures Anti-Inflammatory Agents Apoptosis Cell Count medicine.disease_cause Antioxidants 0302 clinical medicine retinal ganglion cell chemistry.chemical_classification reactive oxygen species rho-Associated Kinases Chemistry ischemic optic neuropathy Immunohistochemistry medicine.anatomical_structure Retinal ganglion cell Intravitreal Injections Optic nerve medicine.medical_specialty Blotting Western Neuroprotection 03 medical and health sciences Internal medicine medicine In Situ Nick-End Labeling Animals Optic Neuropathy Ischemic Rats Wistar Protein Kinase Inhibitors Rho kinase inhibitor Reactive oxygen species Retina Eye Movements Strabismus Amblyopia and Neuro-Ophthalmology Retinal pigment epithelium Superoxide Dismutase Ischemic optic neuropathy medicine.disease Rats Disease Models Animal Oxidative Stress 030104 developmental biology Endocrinology Zonula Occludens-1 Protein Evoked Potentials Visual sense organs 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 |
| Popis: | Purpose This study investigated the neuroprotective effects of administration of ROCK inhibitor E212 on ischemic optic neuropathy. Methods Rats received an intravitreal injection of either E212 or PBS immediately after optic nerve infarct. The oxidative stress in the retina was detected by performing superoxide dismutase activity and CellROX assays. The integrity of retinal pigment epithelium was determined by staining of zona occludens 1. The visual function, retinal ganglion cell (RGC) density, and RGC apoptosis were determined by using flash visual-evoked potential analysis, retrograde FluoroGold labeling, and TdT-dUTP nick end-labeling assay. Macrophage infiltration was detected by staining for ED1. The protein levels of TNF-α, p-CRMP, p-AKT1, p-STAT3, and CD206 were evaluated using Western blotting. Results Administration of E212 resulted in a 1.23-fold increase in the superoxide dismutase activity of the retina and 2.28-fold decrease in RGC-produced reactive oxygen species as compared to the levels observed upon treatment with PBS (P < 0.05). Moreover, E212 prevented the disruption of the blood-retinal barrier (BRB) in contrast to PBS. The P1-N2 amplitude and RGC density in the E212-treated group were 1.75- and 2.05-fold higher, respectively, than those in the PBS-treated group (P < 0.05). The numbers of apoptotic RGCs and macrophages were reduced by 2.93- and 2.54-fold, respectively, in the E212-treated group compared with those in the PBS-treated group (P < 0.05). The levels of p-AKT1, p-STAT3, and CD206 were increased, whereas those of p-PTEN, p-CRMP2, and TNF-α were decreased after treatment with E212 (P < 0.05). Conclusions Treatment with E212 suppresses oxidative stress, BRB disruption, and neuroinflammation to protect the visual function in ischemic optic neuropathy. |
| Databáze: | OpenAIRE |
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