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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.

Kinnunen K, Heinonen SE, Kalesnykas G, Laidinen S, Uusitalo-Järvinen H, Uusitalo H, Ylä-Herttuala S - Mol. Vis. (2013)

Bottom Line: 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.Moreover, photoreceptor atrophy and thinning of the outer nuclear layer were present.Caspase-3 staining was positive in the photoreceptor inner segment.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.

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.

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Related in: MedlinePlus

No neovessel formation was observed in low-density lipoprotein receptor–deficient apolipoprotein B-100-only mice overexpressing insulin-like growth factor II (IGF-II/LDLR–/–ApoB100/100). Retinal whole mounts reveal a normal retinal vasculature in both 15-month-old IGF-II/LDLR–/– ApoB100/100 mice and LDLR–/–ApoB100/100 mice (A and B) fed with a normal diet. Lectin staining of capillaries (C, left panel), Chondroitin Sulfate Proteoglycan (NG2) staining for pericytes (C, middle panel), and a merged image (C, right panel) of control LDLR–/–ApoB100/100 (C, upper panel) and IGF-II/LDLR–/–ApoB100/100 mice (C, lower panel) reveal a normal retinal vasculature in both 15-month-old IGF-II/LDLR–/–ApoB100/100 mice and LDLR–/–ApoB100/100 mice (A and B) fed with a normal diet. The scale bar is 50 µm in A and B, and 25 µm in C.
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f1: No neovessel formation was observed in low-density lipoprotein receptor–deficient apolipoprotein B-100-only mice overexpressing insulin-like growth factor II (IGF-II/LDLR–/–ApoB100/100). Retinal whole mounts reveal a normal retinal vasculature in both 15-month-old IGF-II/LDLR–/– ApoB100/100 mice and LDLR–/–ApoB100/100 mice (A and B) fed with a normal diet. Lectin staining of capillaries (C, left panel), Chondroitin Sulfate Proteoglycan (NG2) staining for pericytes (C, middle panel), and a merged image (C, right panel) of control LDLR–/–ApoB100/100 (C, upper panel) and IGF-II/LDLR–/–ApoB100/100 mice (C, lower panel) reveal a normal retinal vasculature in both 15-month-old IGF-II/LDLR–/–ApoB100/100 mice and LDLR–/–ApoB100/100 mice (A and B) fed with a normal diet. The scale bar is 50 µm in A and B, and 25 µm in C.

Mentions: Diabetes in the IGF-II/LDLR–/–ApoB100/100 mice did not induce retinal neovessel formation on normal chow (Figure 1) or a Western diet (data not shown). No early microvascular diabetic changes, such as micro-aneurysms, hemorrhages, intraretinal microvascular abnormalities or lipid exudates were found in the retinas of IGF-II/LDLR–/–ApoB100/100 or control mice.


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.

Kinnunen K, Heinonen SE, Kalesnykas G, Laidinen S, Uusitalo-Järvinen H, Uusitalo H, Ylä-Herttuala S - Mol. Vis. (2013)

No neovessel formation was observed in low-density lipoprotein receptor–deficient apolipoprotein B-100-only mice overexpressing insulin-like growth factor II (IGF-II/LDLR–/–ApoB100/100). Retinal whole mounts reveal a normal retinal vasculature in both 15-month-old IGF-II/LDLR–/– ApoB100/100 mice and LDLR–/–ApoB100/100 mice (A and B) fed with a normal diet. Lectin staining of capillaries (C, left panel), Chondroitin Sulfate Proteoglycan (NG2) staining for pericytes (C, middle panel), and a merged image (C, right panel) of control LDLR–/–ApoB100/100 (C, upper panel) and IGF-II/LDLR–/–ApoB100/100 mice (C, lower panel) reveal a normal retinal vasculature in both 15-month-old IGF-II/LDLR–/–ApoB100/100 mice and LDLR–/–ApoB100/100 mice (A and B) fed with a normal diet. The scale bar is 50 µm in A and B, and 25 µm in C.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3733910&req=5

f1: No neovessel formation was observed in low-density lipoprotein receptor–deficient apolipoprotein B-100-only mice overexpressing insulin-like growth factor II (IGF-II/LDLR–/–ApoB100/100). Retinal whole mounts reveal a normal retinal vasculature in both 15-month-old IGF-II/LDLR–/– ApoB100/100 mice and LDLR–/–ApoB100/100 mice (A and B) fed with a normal diet. Lectin staining of capillaries (C, left panel), Chondroitin Sulfate Proteoglycan (NG2) staining for pericytes (C, middle panel), and a merged image (C, right panel) of control LDLR–/–ApoB100/100 (C, upper panel) and IGF-II/LDLR–/–ApoB100/100 mice (C, lower panel) reveal a normal retinal vasculature in both 15-month-old IGF-II/LDLR–/–ApoB100/100 mice and LDLR–/–ApoB100/100 mice (A and B) fed with a normal diet. The scale bar is 50 µm in A and B, and 25 µm in C.
Mentions: Diabetes in the IGF-II/LDLR–/–ApoB100/100 mice did not induce retinal neovessel formation on normal chow (Figure 1) or a Western diet (data not shown). No early microvascular diabetic changes, such as micro-aneurysms, hemorrhages, intraretinal microvascular abnormalities or lipid exudates were found in the retinas of IGF-II/LDLR–/–ApoB100/100 or control mice.

Bottom Line: 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.Moreover, photoreceptor atrophy and thinning of the outer nuclear layer were present.Caspase-3 staining was positive in the photoreceptor inner segment.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.

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.

Show MeSH
Related in: MedlinePlus