Abstract
Purpose :
The immune-privileged status of the eye results from the need to maintain its vasculature outside of the central visual axis, presenting challenges to the recruitment of immune cells in response to injury or pathogenesis. Tissue resident immune cells play a key role in this process as the sentinels of danger. Their activation can lead to induction of an inflammatory response and the subsequent recruitment of immune cells with immunomodulatory functions to maintain/restore homeostasis. In the Experimental Autoimmune Uveitis (EAU) mouse model the peak of disease occurs at day 14 post-induction, by which time immunomodulatory cells are recruited to the lens capsule surface. Here, we investigated the spatial and temporal activation of resident immune cells in the eye following induction of EAU.
Methods :
EAU was induced in C57BL/6 mice by immunization with a peptide encoding a uveitogenic epitope of the interphotoreceptor retinoid-binding protein (hIRBPP651-670). At days 3, 8, 11, and 14 post-induction of EAU, whole eyes were fixed and prepared for cryosectioning. 30µm sections were prepared and immunolabeled for molecules such as MHCII, whose expression is characteristic of activated Antigen Presenting Cells (APCs). Sections were co-labeled with fluorescent-tagged phalloidin to detect F-actin, which delineates the cytoarchitecture of eye tissues, and with DAPI to detect nuclei. Images were acquired by confocal microscopy and were analyzed using Imaris software.
Results :
MHCII-positive cells with properties of professional antigen presenting cells were detected in different regions of the eye, including the retina and cornea, as early as 3 days post-induction of EAU. Activation of the resident immune cells of the lens occurred later, and was temporally linked to the recruitment of immunomodulatory cells to the surface of the lens capsule.
Conclusions :
Resident immune cells were rapidly activated in different ocular tissues following the induction of EAU. Their activation could play a role both in inducing the inflammatory response and in recruiting regulatory immune cells that could modulate EAU inflammation.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.