Producción CyT
LXXI REUNIÓN CIENTÍFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI) - CD4+ T CELLS DRIVE CORNEAL NERVE DAMAGE BUT ARE DISPENSABLE FOR CORNEAL EPITHELIOPATHY DEVELOPMENT IN THE CONTEXT OF DRY EYE
Congreso
Autoría:
Vereertbrugghen, Alexia ; PIZZANO, MANUELA ; Cernutto, Agostina ; Sabbione, Florencia ; Keitelman, Irene Angelica ; Shiromizu, Maiumi Carolina ; Vera Aguilar, Douglas ; Fuentes, Federico ; Giordano, Mirta ; Trevani, Analia ; Galletti, JeremíasFecha:
2023Editorial y Lugar de Edición:
Nueva Editorial UniversitariaResumen *
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<0.001), midepithelial (-48±24% vs -19±35, p=0.02), and subbasal (-36±16% vs -8±26%,p=0.01) nerve density in wt than in RAG1KO mice. Compared to sham CD4+ Tcell-recipient mice, RAG1KO mice that received CD4+ T cells from DED wt miceshowed: 1) no change in the proliferation rate (p=0.97) and barrier function (day0: 5.8±0.6 vs 4.2±1.0, p=0.06; day 7: 6.3±1.1 vs 5.8±0.4, p=0.45; day 14: 4.7±1.2vs 3.8±0.6, p=0.20; day 21: 4.4±1.4 vs 4.8±0.8, p=0.79; day 28: 3.9±0.5 vs4.5±0.7, p=0.17) of the corneal epithelium; 2) decreased mechanosensitivity (day7: -2±8% vs -10±8%, p=0.006; day 14: -2±9% vs -13±10%, p=0.0005; day 21:-1±10% vs -16±12%, p=0.0045; day 28: +10±8% vs -13±9%, p=0.0001); and3) reduced corneal nerve density at the subapical (-40±18%, p=0.0001), midepithelial (-42±24%, p=0.001), and subbasal (-32±27%, p=0.009) levels.Conclusion: In the absence of CD4+ T cells, the development of corneal epithelialdamage remains unchanged in DED while there is no neurodegeneration. Also,adoptive transfer of DED CD4+ T cells to RAG1KO mice induced the progressiveloss of corneal nervedensity and function but had no effect on the epithelium.Thus, our results indicate that CD4+ T cells drive DED-associated cornealneurodegeneration but are not necessary for the development of epithelialdamage. Información suministrada por el agente en SIGEVAPalabras Clave
NEURODEGENERATIONCD4 T CELLDRY EYE DISEASE