title: Tissue kallikrein (kallidinogenase) protects against retinal ischemic damage in mice.
abstract: Ocular ischemic syndrome is likely stem from retinal ischemia, and which causes visual disorder. The pathological mechanism of ocular ischemic syndrome is still unknown, therefore the optimal treatment for ocular ischemic syndrome remains to be established. Then, this study aimed to evaluate the effects of tissue-derived kallidinogenase in retinal ischemia protection in mice. In the present study, the effects of tissue-derived kallidinogenase (1 or 10 μg/kg, i.v.) on ischemia/reperfusion-induced retinal damage in mice were examined by histological, electrophysiological, and permeability analyses. In addition, we assessed phosphorylation of endothelial nitric oxide synthase (eNOS) and nuclear factor-kappa B (NF-κB), which is closely-involved in ischemic injury and permeability. Moreover, the neuroprotective effect of kallidinogenase in an in vitro model of ischemia induced by oxygen-glucose deprivation or hypoxia was examined. The results indicated that kallidinogenase significantly prevented the decrease in ganglion cell number induced by ischemia/reperfusion. Electroretinogram measurements showed that kallidinogenase significantly prevented the ischemia/reperfusion-induced reductions in a- and b-wave amplitudes seen 5 days after ischemia/reperfusion. Moreover, kallidinogenase significantly inhibited the permeability increase induced by ischemia/reperfusion. Similar to the results in vivo, kallidinogenase significantly inhibited the retinal ganglion cell death induced by oxygen-glucose deprivation. Also, kallidinogenase significantly suppressed the hypoxia-induced increase in permeability. However, these effects observed in vitro disappeared when an eNOS inhibitor was used concurrently. These findings suggest that kallidinogenase may prevent ischemia/reperfusion-induced retinal damage, might be through eNOS activation.
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Ishizuka
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan. Electronic address: hidehara@gifu-pu.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007511:Ischemia / Q000517:prevention & control*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020840:Tissue Kallikreins / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D052250:Nitric Oxide Synthase Type III; D020840:Tissue Kallikreins; D010100:Oxygen
keywords: Electroretinogram; Endothelial nitric oxide synthase; FITC (PubChem CID: 18730); Isoflurane (PubChem CID: 3763); Kallidinogenase; Ketamine (PubChem CID: 15851); L-N5-(1-iminoethyl) ornithine dihydrochloride (PubChem CID: 2733507); Nuclear factor-kappa B; Ocular ischemic syndrome; Paraformaldehyde (PubChem CID: 712); Phenylephrine (PubChem CID: 6041); Retinal ischemia; Tropicamide (PubChem CID: 5593); Xylazine (PubChem CID: 68554)