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Cited by 114Retinal Diseases and TreatmentsRetinal Imaging and AnalysisAngiogenesis and VEGF in Cancer

Characterization of a Mouse Model of Hyperglycemia and Retinal Neovascularization

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Rakoczy, Elizabeth P., Rahman, Ireni S. Ali, Binz, Nicolette, Li, Cai-Rui, Vagaja, Nermina N., de Pinho, Marisa, Lai, Chooi-May·2010·The American Journal of Pathology
DOI 10.2353/ajpath.2010.090883PMC PMC2966820
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Abstract

One of the limitations of research into diabetic retinopathy is the lack of suitable animal models. To study how the two important factors--hyperglycemia and vascular endothelial growth factor--interact in diabetic retinopathy, the Akimba mouse (Ins2AkitaVEGF+/-) was generated by crossing the Akita mouse (Ins2Akita) with the Kimba mouse (VEGF+/+). C57Bl/6 and the parental and Akimba mouse lines were characterized by biometric measurements, histology, immunohistochemistry, and Spectralis Heidelberg retinal angiography and optical coherence tomography. The Akimba line not only retained the characteristics of the parental strains, such as developing hyperglycemia and retinal neovascularization, but developed higher blood glucose levels at a younger age and had worse kidney-body weight ratios than the Akita line. With aging, the Akimba line demonstrated enhanced photoreceptor cell loss, thinning of the retina, and more severe retinal vascular pathology, including more severe capillary nonperfusion, vessel constriction, beading, neovascularization, fibroses, and edema, compared with the Kimba line. The vascular changes were associated with major histocompatibility complex class II+ cellular staining throughout the retina. Together, these observations suggest that hyperglycemia resulted in higher prevalences of edema and exacerbated the vascular endothelial growth factor-driven neovascular and retinal changes in the Akimba line. Thus, the Akimba line could become a useful model for studying the interplay between hyperglycemia and vascular endothelial growth factor and for testing treatment strategies for potentially blinding complications, such as edema.

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  • The trVEGF029 (Kimba) mouse is a humanized transgenic model where the neuroretina overexpresses hVEGFA, leading to neovascularization like human proliferative DR.

    “To this end, we used the trVEGF029 (VEGFA+/-, Kimba) mouse, a humanized transgenic mouse model where the neuroretina overexpresses hVEGFA, leading to neovascularization like human proliferative DR (33).”

    From Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina (2024) · cites this paper as [33]

    The Discussion identifies a human VEGF transgene in Kimba photoreceptors, and the paper reports that transient hVEGF up-regulation causes retinal neovascularization. However, the Discussion describes Kimba’s changes as similar to human nonproliferative DR by eight weeks and says preretinal neovascularization was not observed. The comparison to human proliferative DR therefore overstates the model’s resemblance. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • Kimba mice show chronic disease and all major signs of proliferative retinopathy.

    “it shows chronic disease and all major signs of proliferative retinopathy (33).”

    From Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina (2024) · cites this paper as [33]

    The Discussion says Kimba mice have retinal changes by 8 weeks that remain relatively stable over time, supporting persistent disease. The Clinical and Morphometric Analyses report neovascularization and other retinopathic signs, but say hemorrhages occurred only in Akimba mice and retinal edema affected only a minority of Kimba mice. Thus the claim that Kimba mice show all major signs is too broad. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Rakoczy, E. P., Rahman, I. S. A., Binz, N., Li, C.-R., Vagaja, N. N., de Pinho, M., & Lai, C.-M.
Affiliations
  • The University of Western Australia (AU)
  • Lions Eye Institute (AU)
Corresponding author
Rakoczy, Elizabeth P.
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2010-11
Volume
177
Issue
5
Pages
2659-2670
ISSN
0002-9440 (ISSN-L)
DOI
10.2353/ajpath.2010.090883
PMC
PMC2966820
OpenAlex
W2071671229
Cited by
114
References
2
Citations by year
2026: 4 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 10 · 2020: 12 · 2019: 4 · 2018: 10 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 14 · 2012: 5
FWCI
7.33
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal Of Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UWA Profiles and Research Repository (UWA) (submittedVersion)
Funders
  • Juvenile Diabetes Research Foundation International
  • National Health and Medical Research Council (353599)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
diabetic retinopathy, hyperglycemia, retinal neovascularization, vascular endothelial growth factor, mouse model, retinal edema, photoreceptor loss, MHC class II, retinal angiogenesis, retinal fibrosis
MeSH terms
Animals, Blood Glucose, Body Weight, Disease Models, Animal, Humans, Hyperglycemia, Mice, Inbred C57BL, Retina, Retinal Vessels, Retinal Neovascularization, Vascular Endothelial Growth Factor A, Mice

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