title: Neuroprotective effect of NecroX-5 against retinal degeneration in rodents.
abstract: NecroX-5 is a derivative of cyclopentylamino carboxymethylthiazolylindole (NecroX), an inhibitor of necrosis/necroptosis. NecroX-5 has been shown to scavenge mitochondrial reactive oxygen and nitrogen species, and thus preventing necrotic cell death against various kinds of oxidative stress in several tissues, including the brain. To examine the effect of NecroX-5 on retinal degeneration (RD), RD was induced in Sprague-Dawley rats by an intraperitoneal injection of N-methyl-N-nitrosourea and in BALB/c mice by blue light-emitting diode exposure. Scotopic electroretinography recording was used to evaluate retinal function. For histological evaluation, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling, and immunohistochemistry were performed. Electroretinography recordings showed that a-waves and b-waves were significantly reduced in both RD rats and mice, whereas the amplitudes of both waves were significantly increased in both NecroX-5-treated RD rats and mice compared with untreated RD animals. In hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay, the outer nuclear layer where photoreceptors reside appeared to be more preserved, and there were fewer apoptotic cells in NecroX-5-treated RD retinas than in untreated RD retinas. In addition, immunohistochemistry with antiglial fibrillary acidic protein and anti-8-hydroxy-2'-deoxyguanosine showed lower levels of retinal injury and oxidative stress in NecroX-5-treated RD retinas than in untreated RD retinas. These results indicated that NecroX-5 protects retinal neurons from experimentally induced RD, suggesting that NecroX-5 may have a potential for the treatment of RD as a medication.
authors.affiliation: aDepartment of Anatomy bCatholic Neuroscience Institute cCatholic Institute for Applied Anatomy, College of Medicine, The Catholic University of Korea dGS Eye Clinic, Seoul eGyeongju St Mary's Eye Clinic, Gyeongju fLG Life Sciences Ltd, Daejeon, Korea.
authors.forename: Hyung Il
authors.initials: HI
authors.lastname: Kim
authors.forename: Sun-Sook
authors.initials: SS
authors.lastname: Paik
authors.forename: Gyu Hyun
authors.initials: GH
authors.lastname: Kim
authors.forename: Muyan
authors.initials: M
authors.lastname: Kim
authors.forename: Soon Ha
authors.initials: SH
authors.lastname: Kim
authors.forename: In-Beom
authors.initials: IB
authors.lastname: Kim
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000188:drug therapy*; D013450:Sulfones / Q000627:therapeutic use*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D006576:Heterocyclic Compounds, 4 or More Rings; C574766:NecroX-5; D018696:Neuroprotective Agents; D013450:Sulfones; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine