Limits...
N-methyl-N-nitrosourea-induced retinal degeneration in mice is independent of the p53 gene.

Yoshizawa K, Kuwata M, Kawanaka A, Uehara N, Yuri T, Tsubura A - Mol. Vis. (2009)

Bottom Line: MNU-induced photoreceptor cell loss is due to apoptosis and is a reliable animal model for human retinitis pigmentosa.All MNU-treated mice had significantly decreased retinal thickness and photoreceptor cell ratios at the central and peripheral retina and an increased retinal damage ratio compared to the vehicle-treated control.Because the absence of p53 did not prevent photoreceptor cell loss, we conclude that p53 is not essential for MNU-mediated photoreceptor cell degeneration.

View Article: PubMed Central - PubMed

Affiliation: Second Department of Pathology, Kansai Medical University, Moriguchi, Osaka, Japan. yoshizak@takii.kmu.ac.jp

ABSTRACT

Purpose: A single systemic administration of N-methyl-N-nitrosourea (MNU) causes retinal degeneration involving photoreceptor cell loss within 7 days. MNU-induced photoreceptor cell loss is due to apoptosis and is a reliable animal model for human retinitis pigmentosa. The purpose of this study was to determine if p53 contributes to the development of MNU-induced retinal degeneration in mice.

Methods: Eight-week-old p53(-/-), p53(+/-), and p53(+/+) mice received an intraperitoneal injection of 60 mg/kg bodyweight of MNU. Age-matched p53(+/+) mice received the vehicle only (physiologic saline containing 0.05% acetic acid). Mice were sacrificed and necropsied 7 days after the treatment. Both eyes were examined histologically and morphometrically to determine retinal thickness, photoreceptor cell ratio, and retinal damage ratio.

Results: No mice died during the experiment, but the p53 mice treated with MNU had a statistically significant weight loss compared to the other groups. Histologically, all MNU-treated mice, regardless of p53 gene status, experienced retinal degeneration characterized by photoreceptor cell loss (the disappearance of the outer nuclear layer and photoreceptor layer) in both the central and peripheral retina. All MNU-treated mice had significantly decreased retinal thickness and photoreceptor cell ratios at the central and peripheral retina and an increased retinal damage ratio compared to the vehicle-treated control. The retinal changes caused by MNU in p53(+/+), p53(+/-), and p53(-/-) mice were not significantly different and hence were related to a p53-independent apoptotic mechanism.

Conclusions: Because the absence of p53 did not prevent photoreceptor cell loss, we conclude that p53 is not essential for MNU-mediated photoreceptor cell degeneration.

Show MeSH

Related in: MedlinePlus

Retinal changes 7 days after a single systemic administration of 60 mg/kg N-methyl-N-nitrosourea (MNU) to p53−/−, p53+/−, and p53+/+ mice. In MNU-treated p53−/−, p53+/−, and p53+/+ mice, the outer nuclear layer and photoreceptor layer disappeared in both the peripheral and central retina. Equivalent levels of severe retinal degeneration were detected in MNU-treated p53−/−, p53+/−, and p53+/+ mice. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; PRL, photoreceptor cell layer; and PEL, pigment epithelial cell layer. The sections were stained with hematoxylin and eosin. The scale bar represents 70 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2802295&req=5

f2: Retinal changes 7 days after a single systemic administration of 60 mg/kg N-methyl-N-nitrosourea (MNU) to p53−/−, p53+/−, and p53+/+ mice. In MNU-treated p53−/−, p53+/−, and p53+/+ mice, the outer nuclear layer and photoreceptor layer disappeared in both the peripheral and central retina. Equivalent levels of severe retinal degeneration were detected in MNU-treated p53−/−, p53+/−, and p53+/+ mice. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; PRL, photoreceptor cell layer; and PEL, pigment epithelial cell layer. The sections were stained with hematoxylin and eosin. The scale bar represents 70 μm.

Mentions: Retinal histology was studied 7 days after MNU treatment. In vehicle-treated p53+/+ mice, photoreceptor nuclei at the central retina consisted of more than ten layers of cells, and the peripheral retina consisted of more than seven layers of cells (Figure 2). In contrast, regardless of p53 status, the outer nuclear layer of MNU-treated mice contained no photoreceptor nuclei or only a few layers of nuclei at both the central and peripheral retina (Figure 2). The remaining photoreceptor nuclei in MNU-treated mice were densely stained; their chromatin was clumped, and large basophilic bodies were present in between the remaining photoreceptor nuclei. The MNU-induced changes were restricted to photoreceptor cells.


N-methyl-N-nitrosourea-induced retinal degeneration in mice is independent of the p53 gene.

Yoshizawa K, Kuwata M, Kawanaka A, Uehara N, Yuri T, Tsubura A - Mol. Vis. (2009)

Retinal changes 7 days after a single systemic administration of 60 mg/kg N-methyl-N-nitrosourea (MNU) to p53−/−, p53+/−, and p53+/+ mice. In MNU-treated p53−/−, p53+/−, and p53+/+ mice, the outer nuclear layer and photoreceptor layer disappeared in both the peripheral and central retina. Equivalent levels of severe retinal degeneration were detected in MNU-treated p53−/−, p53+/−, and p53+/+ mice. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; PRL, photoreceptor cell layer; and PEL, pigment epithelial cell layer. The sections were stained with hematoxylin and eosin. The scale bar represents 70 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2802295&req=5

f2: Retinal changes 7 days after a single systemic administration of 60 mg/kg N-methyl-N-nitrosourea (MNU) to p53−/−, p53+/−, and p53+/+ mice. In MNU-treated p53−/−, p53+/−, and p53+/+ mice, the outer nuclear layer and photoreceptor layer disappeared in both the peripheral and central retina. Equivalent levels of severe retinal degeneration were detected in MNU-treated p53−/−, p53+/−, and p53+/+ mice. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; PRL, photoreceptor cell layer; and PEL, pigment epithelial cell layer. The sections were stained with hematoxylin and eosin. The scale bar represents 70 μm.
Mentions: Retinal histology was studied 7 days after MNU treatment. In vehicle-treated p53+/+ mice, photoreceptor nuclei at the central retina consisted of more than ten layers of cells, and the peripheral retina consisted of more than seven layers of cells (Figure 2). In contrast, regardless of p53 status, the outer nuclear layer of MNU-treated mice contained no photoreceptor nuclei or only a few layers of nuclei at both the central and peripheral retina (Figure 2). The remaining photoreceptor nuclei in MNU-treated mice were densely stained; their chromatin was clumped, and large basophilic bodies were present in between the remaining photoreceptor nuclei. The MNU-induced changes were restricted to photoreceptor cells.

Bottom Line: MNU-induced photoreceptor cell loss is due to apoptosis and is a reliable animal model for human retinitis pigmentosa.All MNU-treated mice had significantly decreased retinal thickness and photoreceptor cell ratios at the central and peripheral retina and an increased retinal damage ratio compared to the vehicle-treated control.Because the absence of p53 did not prevent photoreceptor cell loss, we conclude that p53 is not essential for MNU-mediated photoreceptor cell degeneration.

View Article: PubMed Central - PubMed

Affiliation: Second Department of Pathology, Kansai Medical University, Moriguchi, Osaka, Japan. yoshizak@takii.kmu.ac.jp

ABSTRACT

Purpose: A single systemic administration of N-methyl-N-nitrosourea (MNU) causes retinal degeneration involving photoreceptor cell loss within 7 days. MNU-induced photoreceptor cell loss is due to apoptosis and is a reliable animal model for human retinitis pigmentosa. The purpose of this study was to determine if p53 contributes to the development of MNU-induced retinal degeneration in mice.

Methods: Eight-week-old p53(-/-), p53(+/-), and p53(+/+) mice received an intraperitoneal injection of 60 mg/kg bodyweight of MNU. Age-matched p53(+/+) mice received the vehicle only (physiologic saline containing 0.05% acetic acid). Mice were sacrificed and necropsied 7 days after the treatment. Both eyes were examined histologically and morphometrically to determine retinal thickness, photoreceptor cell ratio, and retinal damage ratio.

Results: No mice died during the experiment, but the p53 mice treated with MNU had a statistically significant weight loss compared to the other groups. Histologically, all MNU-treated mice, regardless of p53 gene status, experienced retinal degeneration characterized by photoreceptor cell loss (the disappearance of the outer nuclear layer and photoreceptor layer) in both the central and peripheral retina. All MNU-treated mice had significantly decreased retinal thickness and photoreceptor cell ratios at the central and peripheral retina and an increased retinal damage ratio compared to the vehicle-treated control. The retinal changes caused by MNU in p53(+/+), p53(+/-), and p53(-/-) mice were not significantly different and hence were related to a p53-independent apoptotic mechanism.

Conclusions: Because the absence of p53 did not prevent photoreceptor cell loss, we conclude that p53 is not essential for MNU-mediated photoreceptor cell degeneration.

Show MeSH
Related in: MedlinePlus