June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Imaging retinal microglial cell dynamics in healthy and diseased eyes in vivo with adaptive optics
Author Affiliations & Notes
  • Yuhua Rui
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
    Eye Center of Xiangya Hospital, Xiangya Hospital Central South University, Changsha, Hunan, China
  • Daniel MW Lee
    Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, Pennsylvania, United States
  • Min Zhang
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Valerie Snyder
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Elena Gofas
    INSERM, CNRS, Institut de la Vision, Sorbonne Universite, Paris, Île-de-France, France
    INSERM-DGOS CIC 1423, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, Île-de-France, France
  • Pedro Mecê
    DOTA, ONERA, Universite Paris-Saclay, Saint-Aubin, Île-de-France, France
  • Rashmi Raghuraman
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Sanya Yadav
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Pavan Tiruveedhula
    School of Optometry, University of California Berkeley, Berkeley, California, United States
  • Kate Grieve
    INSERM, CNRS, Institut de la Vision, Sorbonne Universite, Paris, Île-de-France, France
    INSERM-DGOS CIC 1423, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris, Île-de-France, France
  • Marie-Helene Errera
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Ethan A Rossi
    Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
    Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Yuhua Rui None; Daniel Lee None; Min Zhang None; Valerie Snyder None; Elena Gofas None; Pedro Mecê None; Rashmi Raghuraman None; Sanya Yadav None; Pavan Tiruveedhula None; Kate Grieve None; Marie-Helene Errera None; Ethan Rossi None
  • Footnotes
    Support  This work was supported by departmental startup funds from the University of Pittsburgh to Ethan A. Rossi, a grant from Foundation Fighting Blindness (PPA-081900772-INSERM), NIH CORE Grant P30 EY08098 to the University of Pittsburgh Department of Ophthalmology, the Eye and Ear Foundation of Pittsburgh, and from an unrestricted grant from Research to Prevent Blindness, New York, N.Y. USA.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 388 – F0426. doi:
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    • Get Citation

      Yuhua Rui, Daniel MW Lee, Min Zhang, Valerie Snyder, Elena Gofas, Pedro Mecê, Rashmi Raghuraman, Sanya Yadav, Pavan Tiruveedhula, Kate Grieve, Marie-Helene Errera, Ethan A Rossi; Imaging retinal microglial cell dynamics in healthy and diseased eyes in vivo with adaptive optics. Invest. Ophthalmol. Vis. Sci. 2022;63(7):388 – F0426.

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

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Abstract

Purpose : We recently showed that a refined sequential detection pattern for multi-offset adaptive optics scanning light ophthalmoscopy (AOSLO) can increase the contrast of weakly scattering inner retinal structures, including presumed microglial cells. However, sequential detection was still time-consuming, preventing dynamics from being monitored over short intervals (< 3 mins). Here we show that fiber-bundle (FB) detection AOSLO overcomes this limitation to reveal microglia and immune cell dynamics in healthy and diseased retinas.

Methods : We designed and implemented a custom 7-fiber optical FB in AOSLO that allows for simultaneous confocal and multi-offset detection. We imaged the nerve fiber layer at several locations at multiple timepoints (from minutes to weeks) in 5 healthy participants and in 3 patients with ocular syphilis or uveitis. Microglia and immune cells were manually segmented for quantification.

Results : Fiber-bundle detection reduced single acquisition time to 10-20 sec, permitting improved imaging over larger areas and monitoring of dynamics over short intervals. Microglia in healthy retinas ranged in size from 7 to 19 μm (mean:13 μm) and appeared in two distinct morphologies including rounded cells and elongated cells with visible processes. Microglia moved slowly in healthy eyes (0.05 μm/sec on average), but their motility was increased in patients with active infections or inflammation up to 0.34 μm/sec. Macrophage-like cells containing granular internal structures were seen in an eye with acute syphilitic posterior placoid chorioretinitis. Images were acquired at multiple time points during treatment, decreases in the quantity and motility of microglia were correlated with improvements of vision and other biomarkers. Microglia activity was apparent in an eye affected by acute retinal vasculitis but absent in another patient’s eye affected by a chronic course of retinal vasculitis that was quiescent at the time of imaging.

Conclusions : FB-AOSLO has revealed the fine-scale structure and dynamics of microglia in the retina during active infection and inflammation in the living eye for the first time. FB-AOSLO offers promise as a powerful tool for detecting and monitoring retinal inflammation and infection in the living eye over short timescales. FB-AOSLO may be useful for distinguishing cases of active infection/inflammation and for evaluating response to treatment.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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