title: Nmnat 1: a Security Guard of Retinal Ganglion Cells (RGCs) in Response to High Glucose Stress.
abstract: OBJECTIVE
  Retinal neurodegeneration is an early event in the pathological process of diabetic retinopathy (DR). Retinal ganglion cell (RGC) injury is an important pathological feature during neurodegenerative process. Protecting RGCs from high glucose-induced injury is a promising strategy for delaying or hindering diabetes mellitus-related retinal neuropathy. This study aims to investigate the role of Nmnat1, an enzyme which catalyzes a key step in the biosynthesis of nicotinamide adenine dinucleotide (NAD), in high glucose-induced RGC injury.
  
  
  METHODS
  Western blot and immunofluorescence analysis was conducted to detect Nmnat1 expression pattern in the retina and RGC-5 cell. MTT assay, Hoechst staining, trypan blue staining, and calcein-AM/ propidium iodide (PI) staining was conducted to determine the effect of Nmnat1 knockdown on RGC-5 cell function. Microarray and bioinformatics analysis was conducted to identify potential signaling pathways affected by Nmnat1 knockdown. Pharmacological intervention, molecular intervention, and in vitro experiments were conducted to reveal molecular mechanism of Nmnat1-mediated protective effect on RGC-5 cell function.
  
  
  RESULTS
  Nmnat1 is constitutively expressed in retina and RGC-5 cells. Nmnat1 knockdown aggravates RGC injury, and accelerates the development of RGC-5 cell apoptosis upon high glucose stress. MAPK signaling is the primary signaling pathway affected by Nmnat1 knockdown. Under high glucose stress, Nmnat1 knockdown leads to p38-MAPK signaling inactivation. p38-MAPK pathway inhibitor strongly blocks Nmnat1-mediated protective effect on RGC-5 cell function.
  
  
  CONCLUSIONS
  Nmnat1 protects RGC against high glucose-induced injury via p38-MAPK signaling pathway. Nmnat1 may serve as a neuroprotective target for diabetes mellitus-related retinal neuropathy.
authors.forename: Rong-Mei
authors.initials: RM
authors.lastname: Zhou
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.forename: Jin
authors.initials: J
authors.lastname: Yao
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Kun
authors.initials: K
authors.lastname: Shan
authors.forename: Xiu-Miao
authors.initials: XM
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.forename: Biao
authors.initials: B
authors.lastname: Yan
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*
chemical_list: D034741:RNA, Small Interfering; C529444:NMNAT1 protein, rat; D009612:Nicotinamide-Nucleotide Adenylyltransferase; D005947:Glucose