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.
OBJECTIVE
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.
Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Kati
K
Kinnunen
Suvi E
SE
Heinonen
Giedrius
G
Kalesnykas
Svetlana
S
Laidinen
Hannele
H
Uusitalo-Järvinen
Hannu
H
Uusitalo
Seppo
S
Ylä-Herttuala
D000818:Animals; D053299:Apolipoprotein B-100 / Q000378:metabolism*; D017209:Apoptosis; D001284:Atrophy; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology; D004032:Diet; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D011973:Receptors, LDL / Q000172:deficiency* / Q000378:metabolism; D012162:Retinal Degeneration / Q000150:complications / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000150:complications / Q000378:metabolism / Q000473:pathology*
D053299:Apolipoprotein B-100; D011973:Receptors, LDL; D007335:Insulin-Like Growth Factor II