title: The natural retinoprotectant chrysophanol attenuated photoreceptor cell apoptosis in an N-methyl-N-nitrosourea-induced mouse model of retinal degenaration.
abstract: Retinitis pigmentosa (RP) is an inherited photoreceptor-degenerative disease, and neuronal degeneration in RP is exacerbated by glial activation. Cassia seed (Jue-ming-zi) is a traditional herbal medicine commonly used to treat ocular diseases in Asia. In this report, we investigated the retina-protective effect of chrysophanol, an active component of Cassia seed, in an N-methyl-N-nitrosourea (MNU)-induced mouse model of RP. We determined that chrysophanol inhibited the functional and morphological features of MNU-induced retinal degeneration using scotopic electroretinography (ERG), optical coherence tomography (OCT), and immunohistochemistry analysis of R/G opsin and rhodopsin. Furthermore, TUNEL assays revealed that chrysophanol attenuated MNU-induced photoreceptor cell apoptosis and inhibited the expression of the apoptosis-associated proteins PARP, Bax, and caspase-3. In addition, chrysophanol ameliorated reactive gliosis, as demonstrated by a decrease in GFAP immunolabeling, and suppressed the activation of matrix metalloproteinase (MMP)-9-mediated gelatinolysis. In vitro studies indicated that chrysophanol inhibited lipopolysaccharide (LPS)-induced iNOS and COX-2 expression in the BV2 mouse microglia cell line and inhibited MMP-9 activation in primary microglia. Our results demonstrate that chrysophanol provided neuroprotective effects and inhibited glial activation, suggesting that chrysophanol might have therapeutic value for the treatment of human RP and other retinopathies.
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Fan-Li
authors.initials: FL
authors.lastname: Lin
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Cheng-Hui
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Ophthalmology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Jau-Der
authors.initials: JD
authors.lastname: Ho
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jing-Lun
authors.initials: JL
authors.lastname: Yen
authors.affiliation: Department of Anatomy, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Chang
authors.affiliation: Department of Neuroscience and Experimental Therapeutics and Institute of Ocular Pharmacology, College of Medicine, Texas A&M Health Science Center, College Station, TX, USA.
authors.forename: George C Y
authors.initials: GC
authors.lastname: Chiou
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: George
authors.initials: G
authors.lastname: Hsiao
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D004596:Electroretinography; D006801:Humans; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D010786:Photoreceptor Cells / Q000187:drug effects / Q000473:pathology; D012160:Retina / Q000187:drug effects* / Q000503:physiopathology; D012162:Retinal Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D041623:Tomography, Optical Coherence
chemical_list: D000880:Anthraquinones; D008770:Methylnitrosourea; C027113:chrysophanic acid