Quantifiable in vivo imaging biomarkers of retinal regeneration by photoreceptor cell transplantation

Ying V. Liu, Simrat K. Sodhi, Gilbert Xue, Derek Teng, Dzhalal Agakishiev, Minda M. McNally, Sarah Harris-Bookman, Caitlin McBride, Gregory J. Konar, Mandeep S. Singh

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Short-term improvements in retinal anatomy are known to occur in preclinical models of photoreceptor transplantation. However, correlative changes over the long term are poorly understood. We aimed to develop a quantifiable imaging biomarker grading scheme, using noninvasive multimodal confocal scanning laser ophthal-moscopy (cSLO) imaging, to enable serial evaluation of photoreceptor transplantation over the long term. Methods: Photoreceptor cell suspensions or sheets from rhodopsin-green fluores-cent protein mice were transplanted subretinally, into either NOD.CB17-Prkdcscid /J or C3H/HeJ-Pde6brd1 mice. Multimodal cSLO imaging was performed serially for up to three months after transplantation. Imaging biomarkers were scored, and a grade was defined for each eye by integrating the scores. Image grades were correlated with immunohis-tochemistry (IHC) data. Results: Multimodal imaging enabled the extraction of quantitative imaging biomark-ers including graft size, GFP intensity, graft length, on-target graft placement, intra-graft lamination, hemorrhage, retinal atrophy, and periretinal proliferation. Migration of transplanted material was observed. Changes in biomarker scores and grades were detected in 14/16 and 7/16 eyes, respectively. A high correlation was found between image grades and IHC parameters. Conclusions: Serial evaluation of multiple imaging biomarkers, when integrated into a per-eye grading scheme, enabled comprehensive tracking of longitudinal changes in photoreceptor cell grafts over time. The application of systematic multimodal in vivo imaging could be useful in increasing the efficiency of preclinical retinal cell transplantation studies in rodents and other animal models. Translational Relevance: By allowing longitudinal evaluation of the same animal over time, and providing quantifiable biomarkers, non-invasive multimodal imaging improves the efficiency of retinal transplantation studies in animal models. Such assays will facilitate the development of cell therapy for retinal diseases.

Original languageEnglish (US)
Article number5
JournalTranslational Vision Science and Technology
Volume9
Issue number7
DOIs
StatePublished - Jun 2020

Keywords

  • Age-related macular degeneration
  • Confocal scanning laser ophthalmoscopy
  • Degenerative retinal diseases
  • Photoreceptor cell
  • Retinal organoid
  • Stem cell therapy
  • Xenotransplantation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Ophthalmology

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