Decrease in retinal neuronal cells in streptozotocin-induced diabetic mice.
OBJECTIVE
Little is known about retinal neuronal loss in the retinas of diabetic mice. The purpose of this study was the quantitative assessment of retinal neural cell number in diabetic mice.


METHODS
Five-week-old C57BL/6 mice were used as a diabetic model with streptozotocin. Mice were studied over the course of 6 and 12 weeks after the onset of diabetes. Intraocular pressure (IOP) was measured with a noninvasive TonoLab tonometer. The retinal ganglion cells (RGCs) were counted at two different time points after the induction of diabetes and examined using the immunofluorescence technique and quantitative analysis.


RESULTS
The diabetic mice had significantly elevated IOP levels at 6 and 12 weeks after the onset of diabetes compared with the age-matched control mice (p<0.01 and p<0.001, respectively). The temporal course of Brn3a+ RGC and Neuronal Nuclei+RGC (NeuN+ RGC) loss induced by intraperitoneal injection of streptozotocin followed a similar trend. At 6 and 12 weeks after the onset of diabetes, the number of Brn3a+ RGCs (p<0.05 at 6 weeks; p<0.001 at 12 weeks) and NeuN+ RGCs (p<0.05 at 6 weeks; p<0.001 at 12 weeks) was significantly lower in diabetic mice than age-matched control mice. In the retinal flatmounts, the number of Brn3a+ RGCs (p<0.05 at 6 weeks, p<0.01 at 12 weeks) was also significantly lower in diabetic mice than control mice. The IOP in diabetic mice was negatively related with RGCs in cross sections. The cut-off value of IOP was 14.2 mmHg for diabetes.


CONCLUSIONS
This is a specific quantitative study of neural cell loss in the retina during diabetes. These data suggest that retinal neural cell reduction occurs in diabetic mice. It indicates that RGC loss may be an important component of diabetic retinopathy.
Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China.
Yang
Y
Yang
Danna
D
Mao
Xinke
X
Chen
Ling
L
Zhao
Qing
Q
Tian
Chenggang
C
Liu
Bo Lei Shanbi
BL
Zhou
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D002452:Cell Count; D004268:DNA-Binding Proteins; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D007429:Intraocular Pressure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis; D009798:Ocular Hypertension; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D014065:Tonometry, Ocular; D050819:Transcription Factor Brn-3A / Q000032:analysis / Q000096:biosynthesis
D015415:Biomarkers; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; C494189:Pou4f1 protein, mouse; D050819:Transcription Factor Brn-3A