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Oxidative stress retards vascular development before neural degeneration occurs in retinal degeneration rd1 mice

Abstract

Purpose

To investigate the role of reactive oxygen species (ROS) in retinal development during the early postnatal stage of rd1 mice.

Methods

Development of the three retinal vascular layers of C57BL/6 J (WT) and C3H/HeN (rd1) mice was evaluated from 9th postnatal day (P9) to P21. Retinal ROS production was semi-quantitatively measured using dihydroethidium fluorescence. Mice were treated with intraperitoneal injections of 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) at a dose of 275 mg/kg body weight, and PBS as the control from P3 to P8.

Results

Rd1 mice showed retardation of retinal vascular development in the deep layer at P9. No significant difference was observed in the outer nuclear layer thickness of rd1 and WT mice. ROS production in the outer nuclear layer of rd1 mice was significantly higher than that in the outer nuclear layer of WT mice at P9, P13, and P17 (P < .05). TEMPOL facilitated the development of the deep vascular layer when compared with injection of PBS.

Conclusions

Retardation of retinal vascular development is observed in rd1 mice; ROS is partially responsible for this finding. When using rd1 mice, we should be aware of this difference in comparison to other retinal degeneration animal models and human pathophysiological changes.

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Acknowledgments

Supported in part by research grants KAKENHI 25861614 from the Japan Society for the Promotion of Science, Tokyo, Japan, the Japan Science and the Technology Agency under a program of development of systems and technology for advanced measurement and analysis.

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Correspondence to Shinichi Fukuda.

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Fukuda, S., Ohneda, O. & Oshika, T. Oxidative stress retards vascular development before neural degeneration occurs in retinal degeneration rd1 mice. Graefes Arch Clin Exp Ophthalmol 252, 411–416 (2014). https://doi.org/10.1007/s00417-013-2551-9

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Keywords

  • Retinal degeneration
  • Vascular attenuation
  • Tempol
  • Free radical
  • rd1 mouse