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Published on: October 21, 2022
Time-lapse in vivo dynamics of human corneal immune cells reveals a density-diffusivity relationship
Zeynab Danesh1, Yiming Xu1, Andrew Carkeet1
1Centre for Vision and Eye Research, Optometry and Vision Science, Queensland University of Technology, Brisbane, QLD, Australia.
Insights
Corneal dendritiform cells migrate randomly, with higher cell density surprisingly increasing their surveyed tissue area. This suggests coordinated immune surveillance in the healthy human cornea.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Dendritiform cells are crucial immune cells residing in the corneal stroma.
- Their homeostatic migratory dynamics are essential for immune surveillance.
- Understanding their movement patterns in vivo is key to comprehending corneal immune responses.
Purpose of the Study:
- To investigate the homeostatic migratory dynamics of naïve dendritiform cells in the human cornea using time-lapse in vivo confocal microscopy (IVCM).
- To determine if the diffusion coefficient (D), representing the surveyed tissue area, correlates with local cell density and morphological parameters.
Main Methods:
- Utilized 2D time-lapse IVCM imaging of the subbasal nerve plexus in 55 healthy adults.
- Tracked dendritiform cells and analyzed trajectories using mean square displacement to calculate displacement metrics and D.
- Assessed relationships between D, local cell density, and cell morphology (area, length, circularity).
Main Results:
- Cell trajectories exhibited isotropic, undirected migration consistent with a stochastic random walk.
- The median diffusion coefficient (D) was 3.05 μm²/min.
- A significant positive association was found between D and local cell density (rho = 0.33, p = 0.013).
Conclusions:
- Provided in vivo evidence of random migration with directional bias for corneal dendritiform cells.
- Observed that higher local cell density was unexpectedly associated with a greater diffusion coefficient (D).
- These findings suggest density-enhanced dispersal patterns indicating coordinated immune surveillance by corneal immune cells, even without inflammatory signals.
Purpose:
We used time-lapse in vivo confocal microscopy (IVCM) combined with random walk modelling to investigate the homeostatic migratory dynamics of naïve dendritiform cells in human cornea. Specifically, we asked whether diffusion coefficient (D), which quantifies the tissue area a cell surveys over time, varies with local cell density and morphological parameters.
Methods:
Two-dimensional time-lapse IVCM imaging was obtained from the subbasal nerve plexus at the corneal whorl of 55 healthy young adults. Dendritiform cells without visible dendrites were tracked at approximately 5-min intervals across three time points. Cell trajectories were analysed using mean square displacement to calculate displacement metrics and D. Relationships between D, local cell density and morphological features (area, length, circularity) were assessed.
Results:
Trajectories from 134 cells demonstrated isotropic, undirected migration consistent with a stochastic random walk. The median of D was 3.05 μm2/min (IQR: 0.81-7.78), while mean displacement and trajectory speeds were 0.93 ± 0.71 μm/min and 1.39 ± 0.69 μm/min, respectively. D showed a significant positive association with local cell density (rho = 0.33, p = 0.013).
Conclusions:
This study provides in vivo real-time evidence that dendritiform cells in the healthy human cornea migrate randomly with a directional bias. Unexpectedly, higher local cell density was associated with greater D, contradicting the classical point that crowding constrains motility. These density-enhanced dispersal patterns suggest that corneal immune cells coordinate immune surveillance, even in the absence of inflammatory cues.
