June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Laser-induced Choroidal Neovascularization in the Yucatan Minipig – Characterization of a Novel Model of Neovascular Age-Related Macular Degeneration
Author Affiliations & Notes
  • Ryan F. Boyd
    Ophthalmology Services, MPI Research, Inc, Mattawan, Michigan, United States
  • Douglas B. Snider
    Anatomic Pathology, MPI Research, Inc, Mattawan, Michigan, United States
  • Krishna Yekkala
    Anatomic Pathology, MPI Research, Inc, Mattawan, Michigan, United States
  • Betsy M. Geddings
    Ophthalmology Services, MPI Research, Inc, Mattawan, Michigan, United States
  • Victoria J. Stevenson
    Ophthalmology Services, MPI Research, Inc, Mattawan, Michigan, United States
  • Ashley Sparkes
    EyeCRO, Oklahoma City, Oklahoma, United States
  • Alexander Quiambao
    EyeCRO, Oklahoma City, Oklahoma, United States
  • Didier J. Nuno
    EyeCRO, Oklahoma City, Oklahoma, United States
  • Rafal Farjo
    EyeCRO, Oklahoma City, Oklahoma, United States
  • Thomas S Vihtelic
    Ophthalmology Services, MPI Research, Inc, Mattawan, Michigan, United States
  • Joshua T Bartoe
    Ophthalmology Services, MPI Research, Inc, Mattawan, Michigan, United States
  • Footnotes
    Commercial Relationships   Ryan Boyd, None; Douglas Snider, None; Krishna Yekkala, None; Betsy Geddings, None; Victoria Stevenson, None; Ashley Sparkes, None; Alexander Quiambao, None; Didier Nuno, None; Rafal Farjo, None; Thomas Vihtelic, None; Joshua Bartoe, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2303. doi:
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      Ryan F. Boyd, Douglas B. Snider, Krishna Yekkala, Betsy M. Geddings, Victoria J. Stevenson, Ashley Sparkes, Alexander Quiambao, Didier J. Nuno, Rafal Farjo, Thomas S Vihtelic, Joshua T Bartoe; Laser-induced Choroidal Neovascularization in the Yucatan Minipig – Characterization of a Novel Model of Neovascular Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2303.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Historically, large animal models of neovascular age-related macular degeneration have been unpredictable, with only 70% of laser-induced choroidal neovascularization (CNV) lesions in non-human primates (NHP) considered clinically relevant. Furthermore, only up to 40% of these CNV lesions are considered ideal, exhibiting Grade IV leakage on fluorescein angiography. This inefficiency leads to excess animal use and high study cost. Previous swine CNV models displayed extensive retinal damage and only minimal choroidal involvement when neovascularization was present. We aimed to create a reproducible, predictable swine model of laser-induced CNV improving efficiency and lowering cost compared to available NHP CNV models.

Methods : Yucatan minipigs were used to optimize laser induction of CNV. Bilaterally, six lesions were created using a 532nm green argon laser under direct visualization with a slit lamp and condensing lens. Follow-up examinations included optical coherence tomography (OCT) and fluorescein angiography (FA) at five day intervals, followed by histopathology at 15 days post-operatively.

Results : Lesions were reliably produced exhibiting rupture of Bruch’s membrane as demonstrated by a focal region of discontinuity of the hyperreflective line representing the retinal pigment epithelium/Bruch’s membrane complex on OCT. These regions showed ingrowth of hyperreflective tissue into the outer retinal layers, as well as hyperfluorescence on FA, both suggestive of fibrovascular proliferation from the choroid into the retina. Histopathological characterization of the lesions supported the in vivo findings with moderate to marked subretinal fibrosis and neovascularization extending from the choroid into the outer nuclear layer. The inner retina was generally unaffected.

Conclusions : The Yucatan minipig is an excellent alternative to other large animal models of neovascular age-related macular degeneration. Similar globe size and retinal anatomy to human patients makes the swine model ideal for characterizing novel investigational molecules targeting proliferative posterior segment disease.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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