July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Development of imaging biomarkers of photoreceptor transplantation outcomes in mice based on confocal scanning laser ophthalmoscopy
Author Affiliations & Notes
  • Ying Liu
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • Simrat Sodhi
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • Karl Hudspith
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • Diana Johnson
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • Mandeep S Singh
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Ying Liu, None; Simrat Sodhi, None; Karl Hudspith, None; Diana Johnson, None; Mandeep Singh, None
  • Footnotes
    Support  The Shulsky Foundation and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5839. doi:
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      Ying Liu, Simrat Sodhi, Karl Hudspith, Diana Johnson, Mandeep S Singh; Development of imaging biomarkers of photoreceptor transplantation outcomes in mice based on confocal scanning laser ophthalmoscopy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5839.

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

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Abstract

Purpose : Short-term improvements in retinal anatomy occur after photoreceptor transplantation in preclinical models of retinitis pigmentosa. However, long-term changes are poorly understood. Confocal laser scanning laser ophthalmoscopy (cSLO), a noninvasive imaging modality, could be used to track long-term retinal changes over time. We aimed to develop biomarkers of photoreceptor graft survival and differentiation in mouse recipients using multimodal cSLO (multicolor reflectance (MR), short-wavelength fluorescence (SWF) and spectral domain optical coherence tomography (SDOCT) modes).

Methods : Fluorescent polystyrene FluoSpheresTM (505ex /515em nm, Invitrogen, USA) were transplanted intravitreally (n=6) or subretinally (n=6) in wild-type C57/BL6J mice. After 1 week, the eyes were imaged with MR and SWF (Spectralis, Heidelberg Engineering, USA). Photoreceptor cells from postnatal day 3–6 mice expressing fused human rhodopsin–green fluorescent protein (from Dr. T. Wensel, Baylor College of Medicine, TX) were subretinally transplanted into NOD.CB17-Prkdcscid/J mice (n=8) and mice homozygous for Pde6brd1 (n=5,C3H/HeJ) (both from Jackson Labs, USA). MR, SWF and SDOCT (Spectralis) were performed at 46, 66 and 86 (selected mice) days after transplantation.

Results : Microspheres were detectable using MR imaging as bright punctate objects in the vitreous and subretinal space, compared with SWF imaging controls. Intraocular GFP+ photoreceptors were detectable by SWF in 9 eyes up to 86 days post transplantation. In 4 eyes, the SWF-positive area and signal intensity changed over time. MR imaging showed recipient retinal thinning, detachment, hemorrhage and pucker at the transplant site. SDOCT imaging tracked changes in the location and internal structure of the graft.

Conclusions : In mouse models, MR, FAF and SDOCT identify different characteristics of transplanted photoreceptor cells. SWF imaging detects photoreceptor placement and survival, whereas MR imaging can detect recipient retinal changes at the transplant site. SDOCT provides structural assessment of the cellular graft. cSLO imaging is a non-invasive assay which could be used to develop multimodal imaging biomarkers for the evaluation of long-term photoreceptor transplantation outcomes in preclinical models.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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