Abstract

Retinal pigment epithelial (RPE) cells are well known to play a central role in the progression of numerous retinal diseases. Changes in the structure and function of these cells thus may serve as sensitive biomarkers of disease onset. While in vivo studies have focused on structural changes, functional ones may better capture cell health owing to their more direct connection to cell physiology. In this study, we developed a method based on adaptive optics optical coherence tomography (AO-OCT) and speckle field dynamics for characterizing organelle motility in individual RPE cells. We quantified the dynamics in terms of an exponential decay time constant, the time required for the speckle field to decorrelate. Using seven normal subjects, we found the RPE speckle field to decorrelate in about 5 s. This result has two fundamental implications for future clinical use. First, it establishes a path for generating a normative baseline to which motility of diseased RPE cells can be compared. Second, it predicts an AO-OCT image acquisition time that is 36 times faster than used in our earlier report for individuating RPE cells, thus a major improvement in clinical efficacy.

Highlights

  • Retinal pigment epithelial (RPE) cells are composed of organelles that are under constant motion as they execute cellular and molecular tasks, which encompass essentially every aspect of RPE cell physiology

  • Bright regularly spaced cells are observed in the inner/outer segment junction (IS/OS) + cone outer segment tip (COST) and RPE images in Fig. 1(C, D) with densities consistent with previously reported histology [34] and in vivo imaging [10]

  • We developed a novel Adaptive optics optical coherence tomography (AO-OCT)-based method for measuring organelle motility in individual RPE cells

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Summary

Introduction

Retinal pigment epithelial (RPE) cells are composed of organelles that are under constant motion as they execute cellular and molecular tasks, which encompass essentially every aspect of RPE cell physiology. Consistent with this, animal studies have shown that diseased RPE cells exhibit abnormal organelle motility [3,4,5], pointing to motility as a potentially sensitive indicator of cell health. How these findings translate to the living human eye remains unknown. AO-OCT delineates RPE cells by taking advantage of the cells’ intrinsic organelle motion to increase cell contrast [10,17], while AO-SLO uses the intrinsic fluorescence of lipofuscin [6,7,14] and melanin [12,13,14], extrinsic fluorescence of an ICG dye [11], or multiply-scattered light (dark-field detection) [8]

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