LDLR-/-ApoB100/100 mice with insulin-like growth factor II overexpression reveal a novel form of retinopathy with photoreceptor atrophy and altered morphology of the retina

Mol Vis. 2013 Aug 4;19:1723-33. Print 2013.

Abstract

Purpose: The aim of this study was to characterize the ocular morphology of low-density lipoprotein receptor-deficient apolipoprotein B-100-only mice, where overexpression of insulin-like growth factor II (IGF-II) has been shown to induce glucose intolerance and increase atherosclerotic lesion progression and calcification.

Methods: Fifteen-month-old mice were examined on a normal chow diet and after 3 months of a high-fat Western diet. IGF-II-negative LDLR(-/-)ApoB(100/100) littermates and C57Bl/6J mice served as controls. In vivo color images of the fundi were obtained, and eyes were processed either for retinal flat mounts for assessment of neovascularization or for paraffin-embedded samples for immunohistochemical analyses.

Results: IGF-II overexpression and the resulting prediabetic phenotype did not induce microvascular damage when assessed in fundus photographs and retinal whole mounts, and the number of capillaries in IGF-II/LDLR(-/-)ApoB(100/100) mice was not significantly different from LDLR(-/-)ApoB(100/100) mice. However, morphology of the inner nuclear, outer plexiform, and outer nuclear layers was altered in the IGF-II/LDLR(-/-)ApoB(100/100) mice. Moreover, photoreceptor atrophy and thinning of the outer nuclear layer were present. Caspase-3 staining was positive in the photoreceptor inner segment. In addition, retinas of the IGF-II/LDLR(-/-)ApoB(100/100) mice displayed reduced rhodopsin positivity, consistent with the decreased number of photoreceptor cells.

Conclusions: This study reports a novel form of retinopathy with photoreceptor atrophy and abundant changes in retinal morphology in a mouse model of prediabetes and atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein B-100 / metabolism*
  • Apoptosis
  • Atrophy
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Cell Count
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diet
  • Immunohistochemistry
  • Insulin-Like Growth Factor II / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Photoreceptor Cells, Vertebrate / metabolism
  • Photoreceptor Cells, Vertebrate / pathology*
  • Receptors, LDL / deficiency*
  • Receptors, LDL / metabolism
  • Retinal Degeneration / complications
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / pathology
  • Retinal Diseases / complications
  • Retinal Diseases / metabolism
  • Retinal Diseases / pathology*

Substances

  • Apolipoprotein B-100
  • Receptors, LDL
  • Insulin-Like Growth Factor II