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A model for the easy assessment of pressure-dependent damage to retinal ganglion cells using cyan fluorescent protein-expressing transgenic mice.

Tsuruga H, Murata H, Araie M, Aihara M - Mol. Vis. (2012)

Bottom Line: Laser-treated eyes showed a significantly higher IOP than control eyes from 1 to 7 weeks (p<0.01).The pressure insult and the RGC density showed a significant negative correlation (y=-0.070x+97.2, r=0.75, p=0.0008).Moreover, the central, middle, and peripheral areas measured from the optic disc and each of four retinal quadrant areas also showed significant negative correlations.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.

ABSTRACT

Purpose: To establish an animal model for the easy assessment of pressure-dependent damage to retinal ganglion cells (RGCs) using the B6.Cg-TgN(Thy1-CFP)23Jrs/J transgenic mouse strain (CFP mouse), which expresses cyan fluorescent protein (CFP) in RGCs, and to evaluate pressure-dependent RGC death.

Methods: In 20 CFP mice, right eyes were selected to receive laser-induced ocular hypertension eye and the contralateral eyes remained untouched to serve as controls. Intraocular pressure (IOP) was measured each week in both eyes using the microneedle method up to 8 weeks. Based on the line plot of time (x) and IOP (y) in laser-treated and control eyes, the area surrounded by both lines (∫ΔIOP(y) dx) was calculated as a surrogate value of the pressure insult. At 9 weeks, eyes were enucleated and RGCs expressing CFP were evaluated histologically in retinal whole mounts. The correlation between pressure insult and RGC density was evaluated in the whole eye, three concentric regions, and four quadrants.

Results: Laser-treated eyes showed a significantly higher IOP than control eyes from 1 to 7 weeks (p<0.01). The pressure insult and the RGC density showed a significant negative correlation (y=-0.070x+97.2, r=0.75, p=0.0008). Moreover, the central, middle, and peripheral areas measured from the optic disc and each of four retinal quadrant areas also showed significant negative correlations. Our data demonstrate that each retinal area was almost evenly damaged by IOP elevation.

Conclusions: Laser photocoagulation causes a chronic elevation of IOP in CFP mice. The use of CFP mice enabled us to easily evaluate pressure-dependent RGC damage. This glaucomatous CFP mouse model may contribute to the molecular analysis of neurodegeneration and the development of neuroprotective drugs for glaucoma with a great increase in experimental efficiency.

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Related in: MedlinePlus

Correlation between the pressure-insult and RGC damage. Regression analysis of A: whole retina, B: central, C: middle, D: peripheral, E: superior, F: temporal, G: inferior, and H: nasal retinal areas. Linear regression analysis revealed a significant negative correlation between the pressure-insult and the RGC survival rate, calculated as a percentage of the laser-treated RGC density compared with the contralateral control in whole retina (r=0.75, p=0.0008), in the area from optic disc (central; r=0.61, p=0.0119, middle; r=0.08, p=0.0002, peripheral; r=0.73, p=0.0012) and each retinal quadrant (superior; r=0.64, p=0.0082, temporal; r=0.61, p=0.0124, inferior; r=0.63, p=0.0086, nasal; r=0.51, p=0.0427).
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f9: Correlation between the pressure-insult and RGC damage. Regression analysis of A: whole retina, B: central, C: middle, D: peripheral, E: superior, F: temporal, G: inferior, and H: nasal retinal areas. Linear regression analysis revealed a significant negative correlation between the pressure-insult and the RGC survival rate, calculated as a percentage of the laser-treated RGC density compared with the contralateral control in whole retina (r=0.75, p=0.0008), in the area from optic disc (central; r=0.61, p=0.0119, middle; r=0.08, p=0.0002, peripheral; r=0.73, p=0.0012) and each retinal quadrant (superior; r=0.64, p=0.0082, temporal; r=0.61, p=0.0124, inferior; r=0.63, p=0.0086, nasal; r=0.51, p=0.0427).

Mentions: The correlation between pressure insult and RGC survival rate was assessed. The pressure insult and the RGC survival rate of the whole retina showed a significant negative correlation (y=-0.070x+97.2, r=0.75, p=0.0008; Figure 9A). Moreover, each area from the optic disc (central [y=-0.071x+99.1, r=0.61, p=0.0119], middle [y=-0.077x+99.4, r=0.80, p=0.0002], and peripheral [y=-0.063x+93.8, r=0.73, p=0.0012]), and each retinal quadrant, (superior [y=-0.086x+103.8, r=0.64, p=0.0082], temporal [y=-0.075x+110.0, r=0.61, p=0.0124], inferior [y=-0.065x+91.3, r=0.63, p=0.0086], and nasal [y=-0.055x+87.8, r=0.51, p=0.0427]) also showed significant negative correlations between the pressure insult and the RGC survival rate (Figure 9B-H). There were no significant differences among the values of the correlation coefficient in seven areas. (p=0.9737) Consequently, our data showed that all retinal areas were evenly damaged. Taken together, the present results demonstrate that induction of chronic IOP elevation in CFP mice results in a significant negative correlation between the pressure insult and RGC survival rate.


A model for the easy assessment of pressure-dependent damage to retinal ganglion cells using cyan fluorescent protein-expressing transgenic mice.

Tsuruga H, Murata H, Araie M, Aihara M - Mol. Vis. (2012)

Correlation between the pressure-insult and RGC damage. Regression analysis of A: whole retina, B: central, C: middle, D: peripheral, E: superior, F: temporal, G: inferior, and H: nasal retinal areas. Linear regression analysis revealed a significant negative correlation between the pressure-insult and the RGC survival rate, calculated as a percentage of the laser-treated RGC density compared with the contralateral control in whole retina (r=0.75, p=0.0008), in the area from optic disc (central; r=0.61, p=0.0119, middle; r=0.08, p=0.0002, peripheral; r=0.73, p=0.0012) and each retinal quadrant (superior; r=0.64, p=0.0082, temporal; r=0.61, p=0.0124, inferior; r=0.63, p=0.0086, nasal; r=0.51, p=0.0427).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3472928&req=5

f9: Correlation between the pressure-insult and RGC damage. Regression analysis of A: whole retina, B: central, C: middle, D: peripheral, E: superior, F: temporal, G: inferior, and H: nasal retinal areas. Linear regression analysis revealed a significant negative correlation between the pressure-insult and the RGC survival rate, calculated as a percentage of the laser-treated RGC density compared with the contralateral control in whole retina (r=0.75, p=0.0008), in the area from optic disc (central; r=0.61, p=0.0119, middle; r=0.08, p=0.0002, peripheral; r=0.73, p=0.0012) and each retinal quadrant (superior; r=0.64, p=0.0082, temporal; r=0.61, p=0.0124, inferior; r=0.63, p=0.0086, nasal; r=0.51, p=0.0427).
Mentions: The correlation between pressure insult and RGC survival rate was assessed. The pressure insult and the RGC survival rate of the whole retina showed a significant negative correlation (y=-0.070x+97.2, r=0.75, p=0.0008; Figure 9A). Moreover, each area from the optic disc (central [y=-0.071x+99.1, r=0.61, p=0.0119], middle [y=-0.077x+99.4, r=0.80, p=0.0002], and peripheral [y=-0.063x+93.8, r=0.73, p=0.0012]), and each retinal quadrant, (superior [y=-0.086x+103.8, r=0.64, p=0.0082], temporal [y=-0.075x+110.0, r=0.61, p=0.0124], inferior [y=-0.065x+91.3, r=0.63, p=0.0086], and nasal [y=-0.055x+87.8, r=0.51, p=0.0427]) also showed significant negative correlations between the pressure insult and the RGC survival rate (Figure 9B-H). There were no significant differences among the values of the correlation coefficient in seven areas. (p=0.9737) Consequently, our data showed that all retinal areas were evenly damaged. Taken together, the present results demonstrate that induction of chronic IOP elevation in CFP mice results in a significant negative correlation between the pressure insult and RGC survival rate.

Bottom Line: Laser-treated eyes showed a significantly higher IOP than control eyes from 1 to 7 weeks (p<0.01).The pressure insult and the RGC density showed a significant negative correlation (y=-0.070x+97.2, r=0.75, p=0.0008).Moreover, the central, middle, and peripheral areas measured from the optic disc and each of four retinal quadrant areas also showed significant negative correlations.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.

ABSTRACT

Purpose: To establish an animal model for the easy assessment of pressure-dependent damage to retinal ganglion cells (RGCs) using the B6.Cg-TgN(Thy1-CFP)23Jrs/J transgenic mouse strain (CFP mouse), which expresses cyan fluorescent protein (CFP) in RGCs, and to evaluate pressure-dependent RGC death.

Methods: In 20 CFP mice, right eyes were selected to receive laser-induced ocular hypertension eye and the contralateral eyes remained untouched to serve as controls. Intraocular pressure (IOP) was measured each week in both eyes using the microneedle method up to 8 weeks. Based on the line plot of time (x) and IOP (y) in laser-treated and control eyes, the area surrounded by both lines (∫ΔIOP(y) dx) was calculated as a surrogate value of the pressure insult. At 9 weeks, eyes were enucleated and RGCs expressing CFP were evaluated histologically in retinal whole mounts. The correlation between pressure insult and RGC density was evaluated in the whole eye, three concentric regions, and four quadrants.

Results: Laser-treated eyes showed a significantly higher IOP than control eyes from 1 to 7 weeks (p<0.01). The pressure insult and the RGC density showed a significant negative correlation (y=-0.070x+97.2, r=0.75, p=0.0008). Moreover, the central, middle, and peripheral areas measured from the optic disc and each of four retinal quadrant areas also showed significant negative correlations. Our data demonstrate that each retinal area was almost evenly damaged by IOP elevation.

Conclusions: Laser photocoagulation causes a chronic elevation of IOP in CFP mice. The use of CFP mice enabled us to easily evaluate pressure-dependent RGC damage. This glaucomatous CFP mouse model may contribute to the molecular analysis of neurodegeneration and the development of neuroprotective drugs for glaucoma with a great increase in experimental efficiency.

Show MeSH
Related in: MedlinePlus