Topical administration of the kappa opioid receptor agonist nalfurafine suppresses corneal neovascularization and inflammation
Abstract Corneal neovascularization (CNV) causes higher-order aberrations, corneal edema, ocular inflammation, and corneal transplant rejection, thereby decreasing visual acuity. In this study, we investigated the effects of topical administration of the kappa opioid receptor agonist nalfurafine (TR...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/3ae6a01079114237a7e64390f3ffeccb |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:3ae6a01079114237a7e64390f3ffeccb |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:3ae6a01079114237a7e64390f3ffeccb2021-12-02T16:45:22ZTopical administration of the kappa opioid receptor agonist nalfurafine suppresses corneal neovascularization and inflammation10.1038/s41598-021-88118-62045-2322https://doaj.org/article/3ae6a01079114237a7e64390f3ffeccb2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88118-6https://doaj.org/toc/2045-2322Abstract Corneal neovascularization (CNV) causes higher-order aberrations, corneal edema, ocular inflammation, and corneal transplant rejection, thereby decreasing visual acuity. In this study, we investigated the effects of topical administration of the kappa opioid receptor agonist nalfurafine (TRK-820) on CNV. To induce CNV, intrastromal corneal sutures were placed on the corneal stroma of BALB/c mice for 2 weeks. Nalfurafine (0.1 µg/2 μL/eye) was topically administered to the cornea once or twice daily after CNV induction. The CNV score, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in neovascularized corneas were evaluated using slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. The mRNA expression of the kappa opioid receptor gene Oprk1 was significantly upregulated following CNV induction. Topical administration of nalfurafine twice daily significantly suppressed CNV and lymphangiogenesis, as well as reduced the mRNA levels of angiogenic and pro-inflammatory factors in the neovascularized corneas. Moreover, nalfurafine administration twice daily reduced the numbers of infiltrating leukocytes, neutrophils, macrophages, and interferon-γ-producing CD4+ T cells in the neovascularized corneas. In this study, we demonstrated that topical administration of nalfurafine suppressed local CNV in a mouse model along with the activation of KOR, suggesting that nalfurafine may prevent and control CNV in humans.Hurramhon ShokirovaTakenori InomataTsuyoshi SaitohJun ZhuKenta FujioYuichi OkumuraAi YanagawaKeiichi FujimotoJaemyoung SungAtsuko EguchiMaria MiuraKen NaginoKunihiko HirosawaMizu KuwaharaYasutsugu AkasakiHiroshi NagaseAkira MurakamiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Hurramhon Shokirova Takenori Inomata Tsuyoshi Saitoh Jun Zhu Kenta Fujio Yuichi Okumura Ai Yanagawa Keiichi Fujimoto Jaemyoung Sung Atsuko Eguchi Maria Miura Ken Nagino Kunihiko Hirosawa Mizu Kuwahara Yasutsugu Akasaki Hiroshi Nagase Akira Murakami Topical administration of the kappa opioid receptor agonist nalfurafine suppresses corneal neovascularization and inflammation |
| description |
Abstract Corneal neovascularization (CNV) causes higher-order aberrations, corneal edema, ocular inflammation, and corneal transplant rejection, thereby decreasing visual acuity. In this study, we investigated the effects of topical administration of the kappa opioid receptor agonist nalfurafine (TRK-820) on CNV. To induce CNV, intrastromal corneal sutures were placed on the corneal stroma of BALB/c mice for 2 weeks. Nalfurafine (0.1 µg/2 μL/eye) was topically administered to the cornea once or twice daily after CNV induction. The CNV score, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in neovascularized corneas were evaluated using slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. The mRNA expression of the kappa opioid receptor gene Oprk1 was significantly upregulated following CNV induction. Topical administration of nalfurafine twice daily significantly suppressed CNV and lymphangiogenesis, as well as reduced the mRNA levels of angiogenic and pro-inflammatory factors in the neovascularized corneas. Moreover, nalfurafine administration twice daily reduced the numbers of infiltrating leukocytes, neutrophils, macrophages, and interferon-γ-producing CD4+ T cells in the neovascularized corneas. In this study, we demonstrated that topical administration of nalfurafine suppressed local CNV in a mouse model along with the activation of KOR, suggesting that nalfurafine may prevent and control CNV in humans. |
| format |
article |
| author |
Hurramhon Shokirova Takenori Inomata Tsuyoshi Saitoh Jun Zhu Kenta Fujio Yuichi Okumura Ai Yanagawa Keiichi Fujimoto Jaemyoung Sung Atsuko Eguchi Maria Miura Ken Nagino Kunihiko Hirosawa Mizu Kuwahara Yasutsugu Akasaki Hiroshi Nagase Akira Murakami |
| author_facet |
Hurramhon Shokirova Takenori Inomata Tsuyoshi Saitoh Jun Zhu Kenta Fujio Yuichi Okumura Ai Yanagawa Keiichi Fujimoto Jaemyoung Sung Atsuko Eguchi Maria Miura Ken Nagino Kunihiko Hirosawa Mizu Kuwahara Yasutsugu Akasaki Hiroshi Nagase Akira Murakami |
| author_sort |
Hurramhon Shokirova |
| title |
Topical administration of the kappa opioid receptor agonist nalfurafine suppresses corneal neovascularization and inflammation |
| title_short |
Topical administration of the kappa opioid receptor agonist nalfurafine suppresses corneal neovascularization and inflammation |
| title_full |
Topical administration of the kappa opioid receptor agonist nalfurafine suppresses corneal neovascularization and inflammation |
| title_fullStr |
Topical administration of the kappa opioid receptor agonist nalfurafine suppresses corneal neovascularization and inflammation |
| title_full_unstemmed |
Topical administration of the kappa opioid receptor agonist nalfurafine suppresses corneal neovascularization and inflammation |
| title_sort |
topical administration of the kappa opioid receptor agonist nalfurafine suppresses corneal neovascularization and inflammation |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/3ae6a01079114237a7e64390f3ffeccb |
| work_keys_str_mv |
AT hurramhonshokirova topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT takenoriinomata topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT tsuyoshisaitoh topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT junzhu topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT kentafujio topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT yuichiokumura topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT aiyanagawa topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT keiichifujimoto topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT jaemyoungsung topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT atsukoeguchi topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT mariamiura topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT kennagino topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT kunihikohirosawa topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT mizukuwahara topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT yasutsuguakasaki topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT hiroshinagase topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation AT akiramurakami topicaladministrationofthekappaopioidreceptoragonistnalfurafinesuppressescornealneovascularizationandinflammation |
| _version_ |
1718383448623677440 |