CD4+ T CELLS DRIVE CORNEAL NERVE DAMAGE BUT ARE DISPENSABLE FOR CORNEAL EPITHELIOPATHY DEVELOPMENT IN THE CONTEXT OF DRY EYE

VEREERTBRUGGHEN, ALEXIA; PIZZANO, MANUELA; CERNUTTO A; SABBIONE F; KEITELMAN I; SHIROMIZU CM; VERA AGUILAR, DOUGLAS; FEDERICO FUENTES; GIORDANO , M; TREVANI A; GALLETTI J

San Luis

Congreso; LXXI Reunión Anual de la Sociedad Argentina de Inmunología (SAI); 2023

Introduction: Dry eye disease (DED) is characterized by a dysfunctional tear film,ocular surface inflammation and damage, and neurosensory abnormalities. CD4+T cells promote disease progression but their relative contribution to epithelialand neural damage in the cornea is unknown.Methods: Surgical DED was induced in recombinase activating gene 1-deficient(RAG1KO) and wild-type (wt) mice. Corneal epithelial integrity and nerve functionwere measured on days 0, 5, and 10 by fluorescein uptake and mechanosensitivity, respectively. Nerve and epithelial morphology was evaluated byconfocal microscopy of corneal whole mounts. CD4+ T cells from DED or shamwt mice were adoptively transferred to RAG1KO mice.Results: wt and RAG1KO DED mice developed comparable ocular desiccation (-37±17% vs -38±18% tear production, p=0.85) and loss of conjunctival goblet cells(- 38±29% vs -47±22%, p=0.75), two cardinal DED signs. Both strains showedcomparable DED-induced changes in corneal epithelial cells: barrier functionworsened (day 0: 4.8±1.5 vs 5.2±1.1, p=0.90; day 5: 12.6±3.5 vs 10.0±3.7,p=0.19; day 10: 14.5±3.1 vs 13.3±3.8, p=0.93) while cell proliferation increased(+66±34% vs +75±36% Ki67+ cells, p=0.93). By contrast, cornealmechanosensitivity progressively dropped in wt but not in RAG1KO mice withDED (day 5: -10±11% vs - 0±11, p=0.05; day 10: -21±14% vs +1±7, p=0.01), andcorneal nerve morphology analysis accompanied these changes. We observed alarger DED-induced decrease in subapical (-54±18% vs -17±24%, p