title: Molecular, anatomical and functional changes in the retinal ganglion cells after optic nerve crush in mice.
abstract: OBJECTIVE
  Optic nerve crush (ONC) and subsequent axonal damage can be used in rodents to study the mechanism of retinal ganglion cell (RGC) degeneration. Here, we examined electroretinograms (ERGs) in post-ONC mice to investigate changes in the positive scotopic threshold response (pSTR). We then compared these changes with molecular and morphological changes to identify early objective biomarkers of RGC dysfunction.
  
  
  METHODS
  Fifty 12-week-old C57BL/6 mice were included. ONC was used to induce axonal injury in the right eye of each animal, with the left eye used as a control. The expression of the RGC markers Brn3a and Brn3b was measured on days 1, 2, 3, 5 and 7 after ONC with quantitative real-time PCR. ERGs were recorded under dark adaptation with the stimulus intensity increasing from -6.2 to 0.43 log cd-s/m(2) on days 1, 2, 3, 5, 7 and 10 after ONC. The pSTR, a- and b-wave amplitudes were measured. Inner retinal thickness around the optic nerve head was measured with spectral-domain optical coherence tomography on days 0, 2, 5, 7 and 10 after ONC.
  
  
  RESULTS
  The expression of Brn3a and Brn3b began to significantly decrease on day 1 and day 2, respectively (P < 0.01). The amplitude of the pSTR underwent rapid, significant deterioration on day 3, after which it fell gradually (P < 0.01), while the a- and b-wave amplitudes remained unchanged throughout the experiment. Inner retinal thickness gradually decreased, with the most significant reduction on day 10 (P < 0.01).
  
  
  CONCLUSIONS
  Decrease in pSTR likely reflected the early loss of RGC function after ONC and that declining expression of RGC-specific genes preceded anatomical and functional changes in the RGCs.
authors.affiliation: Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, Miyagi, 980-8574, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yukita
authors.forename: Shigeki
authors.initials: S
authors.lastname: Machida
authors.forename: Koji M
authors.initials: KM
authors.lastname: Nishiguchi
authors.forename: Satoru
authors.initials: S
authors.lastname: Tsuda
authors.forename: Yu
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yasuda
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Maruyama
authors.forename: Toru
authors.initials: T
authors.lastname: Nakazawa
mesh_terms: D000818:Animals; D003623:Dark Adaptation / Q000502:physiology; D004195:Disease Models, Animal; D004596:Electroretinography; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009409:Nerve Crush / Q000009:adverse effects; D055254:Night Vision / Q000502:physiology; D020221:Optic Nerve Injuries / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012165:Retinal Ganglion Cells / Q000502:physiology*; D041623:Tomography, Optical Coherence; D050819:Transcription Factor Brn-3A / Q000235:genetics; D050820:Transcription Factor Brn-3B / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C494189:Pou4f1 protein, mouse; C085559:Pou4f2 protein, mouse; D012333:RNA, Messenger; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B