title: Retinal whole genome microarray analysis and early morphological changes in the optic nerves of monkeys after an intraorbital nerve irradiated injury.
abstract: OBJECTIVE
  To obtain and analyze early retinal changes at the molecular level 24 h after a radiation injury to the ipsilateral intraorbital nerve using gamma knife surgery (GKS), and to examine the morphological changes in bilateral optic nerves.
  
  
  METHODS
  Unilateral intraorbital optic nerves of three rhesus macaques were treated by GKS with irradiated doses of 15 Gy, while contralateral optic nerves and retinas served as the control. Gene expression profiles of the control and affected retinas were analyzed with Affymetrix Rhesus Macaque Genome arrays. To verify the results, a quantitative real-time polymerase chain reaction (qRT-PCR) was performed to test the expression patterns of five function-known genes. Morphological changes in the bilateral optic nerves were examined using a transmission electron microscope (TEM) and light microscopy. The glial cell reaction in bilateral optic nerves was studied using immunohistochemistry.
  
  
  RESULTS
  Of the probe sets, 1,597 (representing 1,081 genes) met the criteria for differential expression, of which 82 genes were significantly up-or down-regulated in treated retinas. There was prominent upregulation of genes associated with glial cell activation in the treated retina. Genes related to an early inflammatory reaction and to cell death were also significantly regulated in response to a radiation injury to the intraorbital optic nerve. In contrast, the messenger ribonucleic acid (mRNA) expression levels of retinal ganglion cell (RGC)-specific genes were low. Morphologically, cytoplasmic processes of astrocytes in treated nerves were shorter than those of the control and were not straight, while also being accompanied by decreased GFAP immunostaining. More oligodendrocytes and inflammatory cells were apparent in treated nerves than in the control. In addition, swollen mitochondria and slight chromation condensation could be seen in the glial cells of treated nerves.
  
  
  CONCLUSIONS
  We conclude that the current irradiated dose of 15 Gy was sufficient to lead to a radiation injury of the optic nerve and retina. Several transcripts deregulated in retinas after a radiation injury play a key role in radiation-induced neurogenic visual loss, especially for genes associated with RGC, glial cell, and cell death. Glial cells in optic nerves might be the primary target of a radiation injury in the optic nerve.
authors: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, PR China.
authors: Yong
authors: Y
authors: Xia
authors: Jun
authors: J
authors: Chen
authors: Li
authors: L
authors: Xiong
authors: Jiagang
authors: J
authors: Liu
authors: Xuesong
authors: X
authors: Liu
authors: Lu
authors: L
authors: Ma
authors: Qiao
authors: Q
authors: Zhang
authors: Chao
authors: C
authors: You
authors: Jing
authors: J
authors: Chen
authors: Xuyang
authors: X
authors: Liu
authors: Xiaoyu
authors: X
authors: Wang
authors: Yan
authors: Y
authors: Ju
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D016923:Cell Death / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D055106:Genome-Wide Association Study; D007150:Immunohistochemistry; D008253:Macaca mulatta; D008297:Male; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D020411:Oligonucleotide Array Sequence Analysis; D009900:Optic Nerve / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D020221:Optic Nerve Injuries / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects
chemical_list: D012333:RNA, Messenger