September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Evaluation of damaged photoreceptors in a macaque model of viral vector induced retinal degeneration using an AOSLO
Author Affiliations & Notes
  • Sarah Walters
    Institute of Optics, University of Rochester, Rochester, New York, United States
  • Christina Schwarz
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • William S Fischer
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
  • David DiLoreto
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
  • Dasha Nelidova
    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
  • Antonia Drinnenberg
    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
  • Josephine Juettner
    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
  • Botond Roska
    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
  • David R Williams
    Institute of Optics, University of Rochester, Rochester, New York, United States
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • Jennifer J Hunter
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • William H Merigan
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • Footnotes
    Commercial Relationships   Sarah Walters, Polgenix Inc. (F); Christina Schwarz, Polgenix Inc. (F); William Fischer, None; David DiLoreto, None; Dasha Nelidova, None; Antonia Drinnenberg, None; Josephine Juettner, None; Botond Roska, Gensight Biologics (S); David Williams, Canon, Inc. (F), Canon, Inc. (R), Polgenix Inc. (F), University of Rochester (P); Jennifer Hunter, Polgenix Inc. (F), University of Rochester (P); William Merigan, None
  • Footnotes
    Support  Research reported in this publication was supported by the National Eye Institute of the National Institutes of Health under Award Nos. P30 EY001319, U01 EY025497, R01 EY022371, and R01 EY021166. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Inst. of Health.; This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1419118. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.; This study was supported by an Unrestricted Grant to the University of Rochester Department of Ophthalmology from Research to Prevent Blindness, New York, New York.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2219. doi:
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    • Get Citation

      Sarah Walters, Christina Schwarz, William S Fischer, David DiLoreto, Dasha Nelidova, Antonia Drinnenberg, Josephine Juettner, Botond Roska, David R Williams, Jennifer J Hunter, William H Merigan; Evaluation of damaged photoreceptors in a macaque model of viral vector induced retinal degeneration using an AOSLO. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2219.

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

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Abstract

Purpose : Efforts to test efficacy of vision restoration methods can benefit by use of non-human primates, but progress is needed in developing useful models of photoreceptor degeneration. Although clinical imaging such as OCT can be used to assess such models, imaging with an adaptive optics scanning light ophthalmoscope (AOSLO) enables cellular-scale tracking of not only photoreceptor structure but also function. Here, photoreceptor damage in a macaque model of retinal degeneration is characterized using 3 AOSLO imaging modalities: confocal reflectance, two-photon autofluorescence (TPAF), and multi-offset detection (MOD).

Methods : An AAV construct designed to locally damage photoreceptors was administered by subretinal injection into 2 macaque retinas. Pre- and post-injections, OCT images were acquired (Heidelberg Spectralis). In one retina, photoreceptors were imaged with an AOSLO (λ=730nm) in the 3 modalities aforementioned. Confocal reflectance was used to evaluate changes in photoreceptor structure. TPAF (λem=400-550nm), thought to originate primarily from retinol in outer segments (OS), was collected to assess function of photoreceptors. As previously shown, TPAF increase in response to the imaging light demonstrates production of retinoids required for visual function. MOD combined images from orthogonal offset aperture positions to visualize photoreceptor inner segments (IS).

Results : Post injection, OCT showed regions of decreased intensity in the outer retina, suggesting photoreceptor damage. AOSLO images revealed presence of both normal and damaged photoreceptors in regions with decreased intensity in OCT (Fig 1). TPAF was decreased in damaged photoreceptors by 75 ± 3% when compared to normal photoreceptors. Furthermore, there was no detectable increase in TPAF at light onset, unlike normal photoreceptors (Fig 2). MOD images indicated that photoreceptor IS remained in damaged photoreceptors.

Conclusions : Three distinct AOSLO imaging modalities and OCT, taken together, are consistent with loss of photoreceptor OS while IS are preserved. This model of retinal degeneration shows potential for testing efficacy of vision restoration methods, especially those such as optogenetics that capitalize on remaining photoreceptor structure.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Damaged (upper) and normal (lower) photoreceptors imaged with 3 AOSLO modalities

Damaged (upper) and normal (lower) photoreceptors imaged with 3 AOSLO modalities

 

TPAF response to imaging light in damaged and normal photoreceptors

TPAF response to imaging light in damaged and normal photoreceptors

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