Nobiletin protects retinal ganglion cells in models of ocular hypertension in vivo and hypoxia in vitro.
Lab Invest
; 102(11): 1225-1235, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-35804043
ABSTRACT
Glaucoma, a common cause of blindness, is characterized by the progressive loss of retinal ganglion cells (RGCs). Growing evidence suggests that nobiletin (NOB) is a promising neuroprotective drug; however, its effects on glaucomatous neurodegeneration remain unknown. Using rat models of microbead occlusion in vivo and primary RGCs model of hypoxia in vitro, we first demonstrate that NOB reduces RGC apoptosis by a TUNEL assay, Hoechst 33342 staining and FluoroGold (FG) retrograde labeling. This effect does not depend on intraocular pressure (IOP) lowering. Additionally, NOB partially restored the functional and structural damage of inner retinas, attenuated Müller glial activation and oxidative stress caused by ocular hypertension. At 2 weeks after IOP elevation, NOB further enhanced Nrf2/HO-1 pathway in RGCs to withstand the cumulative damage of ocular hypertension. With the administration of HO-1 inhibitor tin-protoporphyrin IX (SnPP), the protective effect of NOB was attenuated. Overall, these results indicate that NOB exerts an outstanding neuroprotective effect on RGCs of glaucomatous neurodegeneration. Besides, interventions to enhance activation of Nrf2/HO-1 pathway can slow the loss of RGCs and are viable therapies for glaucoma.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glaucoma
/
Hipertensão Ocular
/
Fármacos Neuroprotetores
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article