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Category: Angiogenesis and Neovascularization
Animals used for research:   Mouse, Rat  

CNV is a commonly used and popular model to mimic the wet form of age-related macular degeneration (AMD). The model is induced by laser photocoagulation of Bruchs membrane in mice, rats and monkeys. The pathological cascade includes inflammation, angiogenesis and proteolysis (Grossniklaus et al., 2010).

SUMMARY

Animal species

Mice and rats 

Method of induction

Diode laser

Follow-up period

Typically 7-14 days

Route of compound administration

Topical (e.g. eye drops), intravitreal or subretinal injections,  systemic

Read-outs
  1.  In vivo imaging
    • fluorescein angiography (FAG)
    • spectral domain-ocular coherence tomography (SD-OCT)
  2. Morphological assessment (histology, immunohistochemistry, electron microscopy, stereology)
Please contact us, if you would like to receive more information: info@experimentica.com

IMAGES

CNV lesions are longitudinally evaluated in vivo using state-of-the-art in vivo imaging systems (Envisu R2200 and R2210, Leica Microsystems Inc.; Heidelberg Spectralis HRA2, Heidelberg Engineering Inc.) 

Representative examples of FAG and SD-OCT images. Left: FAG image taken at the retinal focus shows vascular leakage of fluorescein at the sites of CNV lesions (yellow arrows). Right: SD-OCT image through the center of a CNV lesion. SD-OCT reveals the presence of neovascularization (blue arrows) and edema/liquid (gray arrow). Bars represent segmentation of retinal layers for the quantification of total retinal thickness (red) or the amount of neovascularization (green).

Reference compound. The CNV model has been validated using a reference compound that provides benchmark values for comparison of the efficacy of test compounds. Representative images from an untreated mouse with CNV induction are shown in the upper two rows. The reference compound significantly reduces CNV-induced pathology compared to the untreated eye.

SELECTED PUBLICATIONS

  1. Ragauskas S, Kielczewski E, Vance J, Kaja S, Kalesnykas G. In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal Neovascularization Model. J Vis Exp (2018). PubMed PMID: 29443029
  2. Kinnunen K, Heinonen SE, Kalesnykas G, Laidinen S, Uusitalo-Järvinen H, Uusitalo H, Ylä-Herttuala S. 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). 19:1723-33. PubMed PMID: 23922490
  3. Viita H, Kinnunen K, Eriksson E, Lähteenvuo J, Babu M, Kalesnykas G, Heikura T, Laidinen S, Takalo T, Ylä-Herttuala S. Intravitreal adenoviral 15-lipoxygenase-1 gene transfer prevents vascular endothelial growth factor A-induced neovascularization in rabbit eyes. Hum Gene Ther (2009).1679-86. PubMed PMID: 19694557.
  4. Kinnunen K, Kalesnykas G, Mähönen AJ, Laidinen S, Holma L, Heikura T, Airenne K, Uusitalo H, Ylä-Herttuala S. Baculovirus is an efficient vector for the transduction of the eye: comparison of baculovirus- and adenovirus-mediated intravitreal vascular endothelial growth factor D gene transfer in the rabbit eye. J Gene Med (2009). 11:382-9. PubMed PMID: 19263462.

REFERENCES

  1. Maciulaitiene R, Ragauskas S, Haapaniemi AM, Kaja S, Januleviciene I, Kalesnykas G. Aflibercept shows strong dose-dependency when administered intravitreally in the mouse CNV model. ARVO 2018, programme #2631.
  2. Grossniklaus HE, Kang SJ, Berglin L. Animal models of choroidal and retinal neovascularization. Prog Retin Eye Res (2010). 29:500-19. PubMed PMID: 20488255.

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