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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

Intraocular pressure of ocular hypertension model eyes. Time courses of IOP in the laser-treated eyes and the contralateral control eyes for 8 weeks are indicated. n=20. Data are mean±standard deviation (SD). The IOP of the treated eyes was significantly higher in each time point compared with the IOP of the sham-operated contralateral eyes by a paired t test. (**p<0.01, *** p<0.001).
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f5: Intraocular pressure of ocular hypertension model eyes. Time courses of IOP in the laser-treated eyes and the contralateral control eyes for 8 weeks are indicated. n=20. Data are mean±standard deviation (SD). The IOP of the treated eyes was significantly higher in each time point compared with the IOP of the sham-operated contralateral eyes by a paired t test. (**p<0.01, *** p<0.001).

Mentions: IOP elevation and duration were different in each eye. Sixteen of 20 treated eyes indicated over 30% IOP elevation for at least one measurement time point. However, 4 of 20 treated eyes indicated less than 30% elevation of IOP. The average IOP of the laser-treated eyes was 29.0±16.2 mmHg (mean±SD) at 1 week, which was markedly elevated compared with that of the nontreated control eyes (control, 13.3±1.1 mmHg). IOP remained significantly higher than that of the control eyes until 7 weeks after laser treatment (p<0.01). The average IOP of control eyes was stable and ranged from 13.3±1.1 to 14.6±1.4 mmHg during the entire 8 week study period. Sixteen (80%) of the 20 treated eyes had more than a 30% IOP increase at 1 week after treatment. At 4 and 8 weeks, 11 (55%) and 7 (35%) of 20 eyes maintained more than a 30% IOP increase and the mean IOPs were 18.9±5.5 mmHg and 17.0±5.9 mmHg, respectively (Figure 5).


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)

Intraocular pressure of ocular hypertension model eyes. Time courses of IOP in the laser-treated eyes and the contralateral control eyes for 8 weeks are indicated. n=20. Data are mean±standard deviation (SD). The IOP of the treated eyes was significantly higher in each time point compared with the IOP of the sham-operated contralateral eyes by a paired t test. (**p<0.01, *** p<0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Intraocular pressure of ocular hypertension model eyes. Time courses of IOP in the laser-treated eyes and the contralateral control eyes for 8 weeks are indicated. n=20. Data are mean±standard deviation (SD). The IOP of the treated eyes was significantly higher in each time point compared with the IOP of the sham-operated contralateral eyes by a paired t test. (**p<0.01, *** p<0.001).
Mentions: IOP elevation and duration were different in each eye. Sixteen of 20 treated eyes indicated over 30% IOP elevation for at least one measurement time point. However, 4 of 20 treated eyes indicated less than 30% elevation of IOP. The average IOP of the laser-treated eyes was 29.0±16.2 mmHg (mean±SD) at 1 week, which was markedly elevated compared with that of the nontreated control eyes (control, 13.3±1.1 mmHg). IOP remained significantly higher than that of the control eyes until 7 weeks after laser treatment (p<0.01). The average IOP of control eyes was stable and ranged from 13.3±1.1 to 14.6±1.4 mmHg during the entire 8 week study period. Sixteen (80%) of the 20 treated eyes had more than a 30% IOP increase at 1 week after treatment. At 4 and 8 weeks, 11 (55%) and 7 (35%) of 20 eyes maintained more than a 30% IOP increase and the mean IOPs were 18.9±5.5 mmHg and 17.0±5.9 mmHg, respectively (Figure 5).

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