Vol 1 No 1 (2018): Current Issue
Research Article

Ocular Phenotype of Mice with Impaired Fibrillin-1 Function on Hypercholesterolemic Apolipoprotein E-Deficient Background

Emmi Kokki
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
Tommi Karttunen
Department of Ophthalmology, Kuopio University Hospital, Finland
Sanna Kettunen
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
Kati Kinnunen
Department of Ophthalmology, Kuopio University Hospital, Finland; Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland;
Guido R.Y. De Meyer
Laboratory of Physiopharmacology, University of Antwerp, Belgium
Seppo Yla-Herttuala
Heart Center and Gene Therapy Unit, Kuopio University Hospital, Finland
Published October 1, 2018
  • Apolipoprotein E,
  • Atherosclerosis,
  • Eye,
  • Fibrillin-1,
  • Marfan syndrome,
  • Mouse model,
  • Retinal vessel occlusion
  • ...More


Aim: Transgenic mice with an elastic fiber mutation (C1039G+/-) in the fibrillin-1 gene and apolipoprotein E deficiency express vulnerable atherosclerotic plaque formation in the aorta and coronary and carotid arteries. The fibrillin-1 gene mutation alone leads to impaired fibrillin-1 function common to Marfan syndrome. The aim was to study for the first time the potential effects of atherosclerosis and vulnerable plaques in mouse eye and spontaneous retinal vessel occlusions in these mice.
Methods: Apolipoprotein E-deficient and fibrillin-1 mutated mice (ApoE-/-/Fbn1C1039G+/-) were used for the study. ApoE-/- littermates served as controls. Optical coherence tomography and fluorescein angiography were used to study the retina and retinal vessels before and after the 12-week high-fat diet. Series of staining were performed to study morphology, apoptosis, glial fibrillary acidic protein activation, collagen formation, inflammatory cell infiltration and drusen formation.
Results: No pathological changes were found in hypercholesterolemic ApoE-/-/Fbn1C1039G+/- mice in imaging studies nor in the histological stainings. There was neither abnormality in the retinal morphology nor any detectable biomarkers.
Conclusion: ApoE-/-/Fbn1C1039G+/- mice did not present the ocular signs of Marfan syndrome.12-week high-fat diet is not sufficient to induce retinal vessel occlusion on 20 to 23 weeks old mice. This indicates that the mechanistic background of retinal vessel occlusion is more complex.