TY - JOUR
T1 - Molecular, anatomical and functional changes in the retinal ganglion cells after optic nerve crush in mice
AU - Yukita, Masayoshi
AU - Machida, Shigeki
AU - Nishiguchi, Koji M.
AU - Tsuda, Satoru
AU - Yokoyama, Yu
AU - Yasuda, Masayuki
AU - Maruyama, Kazuichi
AU - Nakazawa, Toru
N1 - Funding Information:
We thank Ms. Junko Sato for her technical assistance. This work was supported in part by JSPS KAKENHI Grants-in-Aid for Scientific Research B (T.N. 26293372) and for Challenging Exploratory Research (Y.T. 26670263 and T.N. 26670751). This study was also supported by the JST Center for Revitalization Promotion (Y.T. and T.N.).
Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.
PY - 2015/3/7
Y1 - 2015/3/7
N2 - 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.Purpose: 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/m2 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.
AB - 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.Purpose: 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/m2 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.
KW - Axonal injury
KW - Electroretinogram
KW - Glaucoma
KW - Retinal ganglion cell
KW - Scotopic threshold response
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U2 - 10.1007/s10633-014-9478-2
DO - 10.1007/s10633-014-9478-2
M3 - Article
C2 - 25560383
AN - SCOPUS:84925487932
SN - 0012-4486
VL - 130
SP - 149
EP - 156
JO - Documenta Ophthalmologica
JF - Documenta Ophthalmologica
IS - 2
ER -