Abstract
Purpose :
Protecting vision requires effective control of eye inflammation, a process that remains poorly understood. We recently discovered that immune cells in the eyes of mice with EAU migrate to all surfaces of the lens capsule. Prior to our findings, it had not been considered that leukocytes may migrate to the lens, an avascular tissue at the center of the light path, in response to injury or pathologies of the eye. Whether leukocyte recruitment to the lens during EAU may modulate intraocular inflammation is unexplored. Our new studies examine immunoregulatory phenotypes of the Lens Capsule Associated Immune Cells (LC-AICs) in EAU.
Methods :
EAU was induced in C57BL/6J mice by subcutaneous injection of peptide 651-670 of human interphotoreceptor retinoid binding protein. Uveitic eyes were harvested at day 18 and day 35 post disease induction, representing active inflammation and immune resolution, respectively. Eyes were fixed, cryosectioned, and co-immunolabeled with antibodies to CD11b, F4/80, CD68, Arg1, CD206, LY6C, LY6G, CD4, and FoxP3 in various combinations, and imaged by confocal microscopy.
Results :
Immunolocalization analyses revealed phenotypic heterogeneity among LC-AICs at day 18 post induction of EAU, including cells with putative anti-inflammatory, pro-resolution roles including M2 macrophages and regulatory T cells (Treg). At this stage, when inflammation is still high, many recruited CD68+ macrophages expressed the M2 marker Arg1, whereas a minority of CD4+ T cells were positive for FoxP3, a Treg-specific transcription factor. These immunomodulatory phenotypes remained associated with the lens capsule surface in a higher proportion at day 35 when inflammation has already resolved. At this later stage of EAU, Arg1+CD68+ macrophages were also found to co-express CD206, a scavenger receptor responsible for removing inflammatory molecules with mannose motif from circulation. These results are compatible with the notion that LC-AICs may contribute to suppressing inflammation and promoting resolution of EAU.
Conclusions :
We propose that, central in the visual axis, the lens provides a platform for leukocytes to promote resolution of EAU and, by persisting past resolution, help to maintain disease remission.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.