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Decrease in retinal neuronal cells in streptozotocin-induced diabetic mice.

Yang Y, Mao D, Chen X, Zhao L, Tian Q, Liu C, Zhou BL - Mol. Vis. (2012)

Bottom Line: Intraocular pressure (IOP) was measured with a noninvasive TonoLab tonometer.The temporal course of Brn3a+ RGC and Neuronal Nuclei+RGC (NeuN+ RGC) loss induced by intraperitoneal injection of streptozotocin followed a similar trend.It indicates that RGC loss may be an important component of diabetic retinopathy.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China.

ABSTRACT

Purpose: 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.

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Related in: MedlinePlus

Brn3a-labeled retinal ganglion cells in flatmount retinas. Left: Brn3a signal (red); middle: 4’,6’-diamino-2-phenylindole (DAPI) signal (blue); right: superimposition of both images. The density of Brn3a+ RGCs in 6 and 12 weeks’ onset of diabetes and control mice are shown in the images (each visual field represents a 133 μm2 area). All images were obtained at 40× magnification. Bar: 2 μm.
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f4: Brn3a-labeled retinal ganglion cells in flatmount retinas. Left: Brn3a signal (red); middle: 4’,6’-diamino-2-phenylindole (DAPI) signal (blue); right: superimposition of both images. The density of Brn3a+ RGCs in 6 and 12 weeks’ onset of diabetes and control mice are shown in the images (each visual field represents a 133 μm2 area). All images were obtained at 40× magnification. Bar: 2 μm.

Mentions: To further demonstrate the diabetes-induced neuronal loss, we quantitatively analyzed Brn3a+ RGCs by a manual counting process in whole flatmounted retinas (Figure 4). We found that the numbers of Brn3a+ RGCs (170±15.34 versus 193.5±21.38 cells/133 um2 at 6 weeks, p<0.05; 152.2±20.10 versus 194.5±23.29 cells/133 μm2 at 12 weeks, p<0.01) of the diabetic mice were significantly lower than those of the age-matched control mice. Thus, there was an 8% loss over 6 weeks and 14% loss over 12 weeks (Figure 5). The number of Brn3a+ RGCs also showed a significant decrease (p<0.05) at 6-week diabetic mice compared with 12-week diabetic mice.


Decrease in retinal neuronal cells in streptozotocin-induced diabetic mice.

Yang Y, Mao D, Chen X, Zhao L, Tian Q, Liu C, Zhou BL - Mol. Vis. (2012)

Brn3a-labeled retinal ganglion cells in flatmount retinas. Left: Brn3a signal (red); middle: 4’,6’-diamino-2-phenylindole (DAPI) signal (blue); right: superimposition of both images. The density of Brn3a+ RGCs in 6 and 12 weeks’ onset of diabetes and control mice are shown in the images (each visual field represents a 133 μm2 area). All images were obtained at 40× magnification. Bar: 2 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369894&req=5

f4: Brn3a-labeled retinal ganglion cells in flatmount retinas. Left: Brn3a signal (red); middle: 4’,6’-diamino-2-phenylindole (DAPI) signal (blue); right: superimposition of both images. The density of Brn3a+ RGCs in 6 and 12 weeks’ onset of diabetes and control mice are shown in the images (each visual field represents a 133 μm2 area). All images were obtained at 40× magnification. Bar: 2 μm.
Mentions: To further demonstrate the diabetes-induced neuronal loss, we quantitatively analyzed Brn3a+ RGCs by a manual counting process in whole flatmounted retinas (Figure 4). We found that the numbers of Brn3a+ RGCs (170±15.34 versus 193.5±21.38 cells/133 um2 at 6 weeks, p<0.05; 152.2±20.10 versus 194.5±23.29 cells/133 μm2 at 12 weeks, p<0.01) of the diabetic mice were significantly lower than those of the age-matched control mice. Thus, there was an 8% loss over 6 weeks and 14% loss over 12 weeks (Figure 5). The number of Brn3a+ RGCs also showed a significant decrease (p<0.05) at 6-week diabetic mice compared with 12-week diabetic mice.

Bottom Line: Intraocular pressure (IOP) was measured with a noninvasive TonoLab tonometer.The temporal course of Brn3a+ RGC and Neuronal Nuclei+RGC (NeuN+ RGC) loss induced by intraperitoneal injection of streptozotocin followed a similar trend.It indicates that RGC loss may be an important component of diabetic retinopathy.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China.

ABSTRACT

Purpose: 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.

Show MeSH
Related in: MedlinePlus