Abstract
Purpose :
In addition to its role in the maintenance of corneal thickness and transparency, the corneal endothelium is a key contributor to the immunological homeostasis of the eye. Recent evidence indicates that in patients affected by low endothelial cell count, either due to Fuchs endothelial cell dystrophy or bullous keratopathy, the ocular immune privilege is disrupted. AURN001 is a cell therapy including corneal endothelial cells and a Rho kinase inhibitor compound. The manufacturing process and formulation enable the cells to restore corneal thickness and vision in patients affected by corneal dystrophies. We investigated whether AURN001 also exhibits properties required for the maintenance of the immunological homeostasis of the eye.
Methods :
Corneal endothelial cells in AURN001 were tested for their ability to elicit or suppress cellular immune responses. Immune responses were assessed in vitro by co-culturing peripheral blood mononuclear cells (PBMC)in the presence of AURN001 and quantifying cell proliferation and cytokine secretion. Cells in AURN001 were also immunophenotyped for HLA-I, HLA-II, CD11b and CD11c via flow cytometry.
Results :
Corneal endothelial cells present in AURN001 are positive for HLA-I and negative for HLA-II (DQ, DP and DR). Samples were also negative for CD11b and CD11c indicating the absence of corneal resident dendritic cells and macrophages. Immune reactions of PBMCs co-cultured with AURN001 were strongly reduced compared to the immune responses of PBMCs co-cultured with allogeneic PBMCs. In fact, PBMC responses to AURN001 were similar to PBMC responses to autologous PBMCs.
Conclusions :
AURN001 exhibits immunomodulatory properties normally observed in native corneal endothelial cells. This is a major advantage over synthetic implants that may restore corneal thickness but do not restore other key components of ocular biology. Unlike synthetic implants, AURN001 appears able to contribute to the maintenance of the immunological homeostasis of the eye. This study adds evidence that, in addition to helping bridge the global gap in corneal tissue supply, AURN001 provides patients and ophthalmic surgeons with a treatment option that not only improves corneal transparency in the near-term, but also re-establishes components of ocular biology that are necessary for long-term maintenance of vision.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.