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Ocular
Microbiology and Immunology Group
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2026 OMIG Abstract
IKZF1 Overexpression Primes the Ocular Surface for Exaggerated T Cell-Mediated Inflammation Following Ovalbumin-Induced Allergic Eye Disease
Ali Khodor, Yasufumi Tomioka, Carolina Moreira dos Santos, Gabriella Mezzich, Luis Hernandez, Leonardo De Castro, Luca Lucchino, and Victor L. Perez
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
Purpose: To characterize an IKZF1-overexpressing mouse subjected to ovalbumin (OVA)-induced allergic eye disease (AED) as a novel model of T cell-mediated ocular inflammation resembling Stevens–Johnson syndrome (SJS).
Methods: Six wild-type (WT) and six keratin 5-driven IKZF1-overexpressing mice were immunized and challenged with OVA to induce AED. Clinical ocular scores (0-12) were recorded longitudinally and correlated with IKZF1 expression. At the study endpoint, conjunctival (2 eyes/sample) and corneal (4 eyes/sample) tissues were pooled for flow cytometric quantification of infiltrating immune populations. Statistical analyses were performed using the Mann–Whitney U test and Spearman rank correlation.
Results: IKZF1 expression positively correlated with ocular disease severity (Spearman ρ = 0.343, P = 0.04). Even before allergen challenge, IKZF1 mice exhibited a pre-inflammatory corneal immune phenotype characterized by significantly increased CD4+ T cells (120 + 89 vs. 6 + 5), CD8+ T cells (77 + 57 vs. 3 + 2), macrophages (384 + 190 vs. 43 + 30), and mast cells (19 + 9 vs. 3 + 3) compared with WT controls (all P < 0.05). Similarly, they demonstrated increased conjunctival CD4+ T-cell infiltration. Following OVA sensitization and challenge, IKZF1 mice developed significantly greater clinical disease severity than WT mice (IKZF=6.0 + 1.4 vs. WT=4.8 + 1.2, P < 0.05), accompanied by marked increases in conjunctival CD4+ T cells (3329 + 2230 vs. 1223 + 487, P < 0.05), CD8+ T cells (786 + 699 vs. 142 + 52, P < 0.05), and dendritic cells (1380 + 647 vs. 620 + 343, P < 0.05). Macrophages and mast cells increased significantly following OVA challenge in both groups. A similar trend toward increased CD4+ and CD8+ T-cell infiltration and innate immune cell recruitment was observed in the cornea of IKZF1-AED mice.
Conclusions: IKZF1 overexpression establishes a pre-inflammatory ocular immune environment that amplifies OVA-induced AED, resulting in a T cell-rich inflammatory phenotype that recapitulates key immunologic features of ocular Stevens-Johnson syndrome.
Disclosure: N (AK, YT, CMdS, GM, LL, LH, LD)
C (VLP, Alumis, BrightStar, Brill Engine, Dompe, Kala, Oculis, Regeneron, Santen, Sylentis, Thea, BROM, EmmeCell, Grifols, Ocubio)
O(WHO?, Eniale Immunotherapeutics)
Support:
NIH/NEI R01EY030283, NIH/NEI R01EY024484, Research to Prevent Blindness- Unrestricted Grant (GR004596-1)
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