June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Cytokine and angiogenesis factor changes in the eye following laser induction of choroidal neovascularization in nonhuman primates
Author Affiliations & Notes
  • Matthew S Lawrence
    Research, RxGen, Hamden, Connecticut, United States
  • Shaun Cote
    Eleven Biotherapeutics, Cambridge, Massachusetts, United States
  • Michael Goldstein
    Eleven Biotherapeutics, Cambridge, Massachusetts, United States
  • Eric Furfine
    Eleven Biotherapeutics, Cambridge, Massachusetts, United States
  • Anish Kurian
    Research, RxGen, Hamden, Connecticut, United States
  • Wenzheng Hu
    Research, RxGen, Hamden, Connecticut, United States
  • Robin J Goody
    Research, RxGen, Hamden, Connecticut, United States
  • Footnotes
    Commercial Relationships   Matthew Lawrence, RxGen (E); Shaun Cote, Eleven Biotherapeutics (E); Michael Goldstein, Eleven Biotherapeutics (E); Eric Furfine, Eleven Biotherapeutics (I); Anish Kurian, RxGen (E); Wenzheng Hu, RxGen (E); Robin Goody, RxGen (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2258. doi:
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    • Get Citation

      Matthew S Lawrence, Shaun Cote, Michael Goldstein, Eric Furfine, Anish Kurian, Wenzheng Hu, Robin J Goody; Cytokine and angiogenesis factor changes in the eye following laser induction of choroidal neovascularization in nonhuman primates. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2258.

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

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Abstract

Purpose : Disruption of Bruch’s membrane by laser photocoagulation is a validated model of choroidal neovascularization (CNV). In this study early changes in cytokine and angiogenesis factors were profiled in St. Kitts green monkey (Chlorocebus sabaeus) eyes subjected to laser treatment to define potential mediators of CNV complex development.

Methods : CNV was induced in the perimacular region. Six laser spots were symmetrically placed around the fovea with an Iridex Oculight TX 532 nm laser with a duration of 100 ms, spot size 50 µm, power 750 mW by methods previously established to trigger CNV. Color fundus photography, OCT and slit lamp exams were performed immediately after laser treatment to document the lesions, and again prior to sacrifice at either 24 (n=4 eyes) or 72 hours (n = 4 eyes). After collection of vitreous, the neural retina and RPE/choroid were subdissected from 5 mm punch biopsies of the macula, and the temporal and nasal periphery, and the remaining fundus. Samples were analyzed using NHP cytokine and human angiogenesis panels and compared to control eyes receiving no laser treatment (n = 8 eyes).

Results : Laser disruption of Bruch’s membrane was associated with significant differences in select assayed protein concentrations at 24 and 72 post-laser. The putative angiogenesis factor MCP-1 was significantly elevated (P<0.01) in the macular retina while vitreous levels of Flt-1 were also markedly increased. IL-7, IL-8, IL-12 and IFN-g were elevated in both macular and peripheral retina. IFN-g was additionally elevated in the vitreous. Generally, though not consistently, changes were progressive from 24 to 72 hours, and most pronounced in the macula and within the retina rather than RPE/choroid or vitreous.

Conclusions : Multiplex cytokine and angiogenesis factor analysis of retina, RPE/choroid, and vitreous samples revealed early temporal changes in abundance of select proteins following perimacular photocoagulation, suggestive of their involvement in insult recovery and CNV development in a multi-pathway process. Tissues in the closest proximity to disrupted Bruch’s membrane revealed the greatest change, as well as certain soluble factors, further supporting the involvement of the defined proteins in pathogenesis.

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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