Ultrastructural changes in the choriocapillaris of N-methyl-N-nitrosourea-induced retinal degeneration in C57BL/6 mice

Med Mol Morphol. 2020 Dec;53(4):198-209. doi: 10.1007/s00795-020-00246-6. Epub 2020 Jan 30.


N-methyl-N-nitrosourea (MNU) is known to cause apoptosis of photoreceptor cells and changes in retinal pigment epithelium (RPE). However, the changes in choriocapillaris, which nourishes photoreceptor cells by diffusing tissue fluid through RPE, have not been reported in detail. Therefore, we studied the ultrastructural transformation in and around the choriocapillaris to characterize the interdependence between choriocapillaris and surrounding tissue components in a mouse model. Seven-week-old male C57BL/6 mice were given a single intraperitoneal injection of MNU (60 mg/kg of body weight). Perfusion-fixed eyeballs were examined chronologically using immunohistochemistry and electron microscopy until the photoreceptor cells were lost. Sequential ultrastructural changes were observed in photoreceptor cells, RPE, Bruch's membrane, choriocapillaris, and choroidal melanocytes after an MNU injection. The lumens of the choriocapillaris narrowed following dilation, and the vascular endothelium showed structural alterations. When the photoreceptor cells were completely lost, the choriocapillaris appeared to be in a recovery process. Our results suggest that transport abnormality through Bruch's membrane and structural changes in the choroid might have influenced the morphology of choriocapillaris. The thin wall of the choriocapillaris appears to be the cause of the vulnerability with its altered morphology.

Keywords: Choriocapillaris; Endothelial cells; N-methyl-N-nitrosourea; Retinal degeneration; Ultrastructural changes.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Choroid / drug effects
  • Choroid / pathology
  • Choroid / ultrastructure*
  • Disease Models, Animal
  • Humans
  • Injections, Intraperitoneal
  • Male
  • Methylnitrosourea / administration & dosage
  • Methylnitrosourea / toxicity*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Photoreceptor Cells, Vertebrate / drug effects
  • Photoreceptor Cells, Vertebrate / pathology
  • Photoreceptor Cells, Vertebrate / ultrastructure
  • Retinal Degeneration / chemically induced
  • Retinal Degeneration / pathology*
  • Retinal Pigment Epithelium / drug effects
  • Retinal Pigment Epithelium / pathology
  • Retinal Pigment Epithelium / ultrastructure


  • Methylnitrosourea