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Development of a New Mouse Model of Branch Retinal Vein Occlusion and Retinal Neovascularization

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Abstract

Purpose

Retinal neovascularization (NV) is associated with various disorders, such as retinal vein occlusion, diabetic retinopathy, and retinopathy of prematurity, and often causes severe loss of vision. To determine the mechanism of retinal NV and develop new therapy, we developed a mouse model using a photodynamic method.

Methods

C57BL/6 mice were injected with rose bengal via the tail vein, and then selected venous points were photocoagulated.

Results

All eyes demonstrated venous occlusion on day 1, and capillary nonperfusion areas were observed until day 3. Twenty of 33 eyes (60.6%) developed retinal NV on day 14, confirmed by fluorescein isothiocyanate-perfused retinal flat-mounts and immunochemical and histopathological analyses. Reverse transcriptase-polymerase chain reaction showed an increase in the expression of vascular endothelial growth factor at the retina on day 7.

Conclusions

Because of the simplicity, low cost, and feasibility of genetic manipulations, our model is believed to represent an advance in investigating molecular mechanisms and establishing therapy for retinal NV. Jpn J Ophthalmol 2007;51:251–257 @ Japanese Ophthalmological Society 2007

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References

  1. PS Virdi SS Hayreh (1982) ArticleTitleOcular neovascularization with retinal vascular occlusion. I. Association with experimental retinal vein occlusion Arch Ophthalmol 100 331–341 Occurrence Handle6175297 Occurrence Handle1:STN:280:Bi2C2MbmslU%3D

    PubMed  CAS  Google Scholar 

  2. CJ Pournaras M Tsacopoulos K Strommer N Gilodi PM Leuenberger (1990) ArticleTitleExperimental retinal branch vein occlusion in miniature pigs induces local tissue hypoxia and vasoproliferative microangiopathy Ophthalmology 97 1321–1328 Occurrence Handle2243682 Occurrence Handle1:STN:280:By6D2MjgtVE%3D

    PubMed  CAS  Google Scholar 

  3. D Finkelstein S Brem A Patz J Folkman S Miller C Ho-Chen (1977) ArticleTitleExperimental retinal neovascularization induced by intravitreal tumors Am J Ophthalmol 83 660–664 Occurrence Handle868966 Occurrence Handle1:STN:280:CSiC1MbktVU%3D

    PubMed  CAS  Google Scholar 

  4. AN Antoszyk JL Gottlieb RC Casey DL Hatchell R Machemer (1991) ArticleTitleAn experimental model of preretinal neovascularization in the rabbit Invest Ophthalmol Vis Sci 32 46–52 Occurrence Handle1987106 Occurrence Handle1:STN:280:By6C3c%2FhvFc%3D

    PubMed  CAS  Google Scholar 

  5. LE Smith E Wesolowski A McLellan et al. (1994) ArticleTitleOxygen-induced retinopathy in the mouse Invest Ophthalmol Vis Sci 35 101–111 Occurrence Handle7507904 Occurrence Handle1:STN:280:ByuC3s7ntlA%3D

    PubMed  CAS  Google Scholar 

  6. RP Danis Y Yang SJ Massicotte HC Boldt (1993) ArticleTitlePreretinal and optic nerve head neovascularization induced by photodynamic venous thrombosis in domestic pigs Arch Ophthalmol 111 539–543 Occurrence Handle7682408 Occurrence Handle1:STN:280:ByyB38fltVQ%3D

    PubMed  CAS  Google Scholar 

  7. Y Saito L Park SA Skolik et al. (1997) ArticleTitleExperimental preretinal neovascularization by laser-induced venous thrombosis in rats Curr Eye Res 16 26–33 Occurrence Handle9043820 Occurrence Handle10.1076/ceyr.16.1.26.5116 Occurrence Handle1:STN:280:ByiC1MnntlU%3D

    Article  PubMed  CAS  Google Scholar 

  8. DI Ham K Chang H Chung (1997) ArticleTitlePreretinal neovascularization induced by experimental retinal vein occlusion in albino rats Korean J Ophthalmol 11 60–64 Occurrence Handle9283155 Occurrence Handle1:STN:280:ByiH38fmvFU%3D

    PubMed  CAS  Google Scholar 

  9. SG Kang H Chung JY Hyon (1999) ArticleTitleExperimental preretinal neovascularization by laser-induced thrombosis in albino rats Korean J Ophthalmol 13 65–70 Occurrence Handle10761400 Occurrence Handle1:STN:280:DC%2BD3c3isVCltA%3D%3D

    PubMed  CAS  Google Scholar 

  10. CC Lai WC Wu SL Chen et al. (2005) ArticleTitleRecombinant adeno-associated virus vector expressing angiostatin inhibits preretinal neovascularization in adult rats Ophthalmic Res 37 50–56 Occurrence Handle15637422 Occurrence Handle10.1159/000083040 Occurrence Handle1:CAS:528:DC%2BD2MXjsFyrt78%3D

    Article  PubMed  CAS  Google Scholar 

  11. RN Frank MA Mancini (1986) ArticleTitlePresumed retinovitreal neovascularization in dystrophic retinas of spontaneously hypertensive rats Invest Ophthalmol Vis Sci 27 346–355 Occurrence Handle2419273 Occurrence Handle1:STN:280:BimC3sfpvVE%3D

    PubMed  CAS  Google Scholar 

  12. ML Weber MA Mancini RN Frank (1989) ArticleTitleRetinovitreal neovascularization in the Royal College of Surgeons rat Curr Eye Res 8 61–74 Occurrence Handle2468452 Occurrence Handle1:STN:280:BiaB3cbpslE%3D

    PubMed  CAS  Google Scholar 

  13. N Okamoto T Tobe SF Hackett et al. (1997) ArticleTitleTransgenic mice with increased expression of vascular endothelial growth factor in the retina: a new model of intraretinal and subretinal neovascularization Am J Pathol 151 281–291 Occurrence Handle9212753 Occurrence Handle1:CAS:528:DyaK2sXkslartb8%3D

    PubMed  CAS  Google Scholar 

  14. JG Banks RG Board J Carter AD Dodge (1985) ArticleTitleThe cytotoxic and photodynamic inactivation of micro-organisms by Rose Bengal J Appl Bacteriol 58 391–400 Occurrence Handle3997691 Occurrence Handle1:STN:280:BiqB3cjisFQ%3D

    PubMed  CAS  Google Scholar 

  15. RP Danis DP Bingaman Y Yang B Ladd (1996) ArticleTitleInhibition of preretinal and optic nerve head neovascularization in pigs by intravitreal triamcinolone acetonide Ophthalmology 103 2099–2104 Occurrence Handle9003344 Occurrence Handle1:STN:280:ByiC2Mnps1c%3D

    PubMed  CAS  Google Scholar 

  16. RP Danis DP Bingaman M Jirousek Y Yang (1998) ArticleTitleInhibition of intraocular neovascularization caused by retinal ischemia in pigs by PKC beta inhibition with LY333531 Invest Ophthalmol Vis Sci 39 171–179 Occurrence Handle9430559 Occurrence Handle1:STN:280:DyaK1c%2FptVChtg%3D%3D

    PubMed  CAS  Google Scholar 

  17. R D'Amato E Wesolowski LE Smith (1993) ArticleTitleMicroscopic visualization of the retina by angiography with high-molecular-weight fluorescein-labeled dextrans in the mouse Microvasc Res 46 135–142 Occurrence Handle7504160 Occurrence Handle10.1006/mvre.1993.1042

    Article  PubMed  Google Scholar 

  18. CE Hayes IJ Goldstein (1974) ArticleTitleAn alpha-d-galactosyl-binding lectin from Bandeiraea simplicifolia seeds. Isolation by affinity chromatography and characterization J Biol Chem 249 1904–1914 Occurrence Handle4206402 Occurrence Handle1:CAS:528:DyaE2cXktVSltLk%3D

    PubMed  CAS  Google Scholar 

  19. TL Chan P Halasz J Stone (1990) ArticleTitleDevelopment of retinal vasculature in the cat: processes and mechanisms Curr Eye Res 9 459–478

    Google Scholar 

  20. LT Chan J Stone (1991) ArticleTitleFactors determining the migration of astrocytes into the developing retina: migration does not depend on intact axons or patent vessels J Comp Neurol 303 375–386 Occurrence Handle10.1002/cne.903030304

    Article  Google Scholar 

  21. LT Chan S Tout H Hollander J Stone (1992) ArticleTitleVascular changes and their mechanisms in the feline model of retinopathy of prematurity Invest Ophthalmol Vis Sci 33 2128–2147

    Google Scholar 

  22. T Ishibashi H Miller G Orr N Sorgente SJ Ryan (1987) ArticleTitleMorphologic observations on experimental subretinal neovascularization in the monkey Invest Ophthalmol Vis Sci 28 1116–1130 Occurrence Handle2439474 Occurrence Handle1:STN:280:BiiB2cblvVI%3D

    PubMed  CAS  Google Scholar 

  23. T Ishibashi T Murata T Kohno Y Ohnishi H Inomata (1999) ArticleTitlePeripheral choriovitreal neovascularization in proliferative diabetic retinopathy: histopathologic and ultrastructural study Ophthalmologica 213 154–158 Occurrence Handle10202287 Occurrence Handle10.1159/000027411 Occurrence Handle1:STN:280:DyaK1M3hvF2gsQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  24. AP Adamis JW Miller M-T Bernal et al. (1994) ArticleTitleIncreased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy Am J Ophthalmol 118 445–450 Occurrence Handle7943121 Occurrence Handle1:STN:280:ByqD38bmsFM%3D

    PubMed  CAS  Google Scholar 

  25. LP Aiello RL Avery PG Arrigg et al. (1994) ArticleTitleVascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders N Engl J Med 331 1480–1487 Occurrence Handle7526212 Occurrence Handle10.1056/NEJM199412013312203 Occurrence Handle1:STN:280:ByqD2MbisFY%3D

    Article  PubMed  CAS  Google Scholar 

  26. D Shweiki A Itin D Soffer E Keshet (1992) ArticleTitleVascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis Nature 359 843–845 Occurrence Handle1279431 Occurrence Handle10.1038/359843a0 Occurrence Handle1:CAS:528:DyaK38XmsV2gsb4%3D

    Article  PubMed  CAS  Google Scholar 

  27. KH Plate G Breier HA Welch W Risau (1992) ArticleTitleVascular endothelial growth factor is a potential tumor angiogenesis factor in human gliomas in vivo Nature 359 845–848 Occurrence Handle1279432 Occurrence Handle10.1038/359845a0 Occurrence Handle1:CAS:528:DyaK38XmsV2gsb8%3D

    Article  PubMed  CAS  Google Scholar 

  28. JW Miller AP Adamis DT Shima et al. (1994) ArticleTitleVascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model Am J Pathol 145 574–584 Occurrence Handle7521577 Occurrence Handle1:CAS:528:DyaK2cXmvFygtrs%3D

    PubMed  CAS  Google Scholar 

  29. EA Pierce RL Avery ED Foley LP Aiello LEH Smith (1995) ArticleTitleVascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization Proc Natl Acad Sci U S A 92 905–909 Occurrence Handle7846076 Occurrence Handle10.1073/pnas.92.3.905 Occurrence Handle1:CAS:528:DyaK2MXjsVKhsr0%3D

    Article  PubMed  CAS  Google Scholar 

  30. LP Aiello EA Pierce ED Foley et al. (1995) ArticleTitleSuppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins Proc Natl Acad Sci U S A 92 10457–10461 Occurrence Handle7479819 Occurrence Handle10.1073/pnas.92.23.10457 Occurrence Handle1:CAS:528:DyaK2MXptlSjsbw%3D

    Article  PubMed  CAS  Google Scholar 

  31. CA Wilson DL Hatchell (1991) ArticleTitlePhotodynamic retinal vascular thrombosis. Rate and duration of vascular occlusion Invest Ophthalmol Vis Sci 32 2357–2365 Occurrence Handle2071346 Occurrence Handle1:STN:280:By6A3c7pvFI%3D

    PubMed  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan

    Han Zhang, Koh-Hei Sonoda, Hong Qiao, Toru Oshima, Toshio Hisatomi & Tatsuro Ishibashi

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  1. Han Zhang
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  2. Koh-Hei Sonoda
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  3. Hong Qiao
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  4. Toru Oshima
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  5. Toshio Hisatomi
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  6. Tatsuro Ishibashi
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Correspondence to Koh-Hei Sonoda.

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Zhang, H., Sonoda, KH., Qiao, H. et al. Development of a New Mouse Model of Branch Retinal Vein Occlusion and Retinal Neovascularization. Jpn J Ophthalmol 51, 251–257 (2007). https://doi.org/10.1007/s10384-007-0445-2

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  • DOI: https://doi.org/10.1007/s10384-007-0445-2

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