The cellular inflammatory response associated with sulfur mustard induced delayed limbal stem cell deficiency and evaluation of tacrolimus treatment

Elina Berg, David Zadok, Ariel Gore, Maayan Cohen, Hila Gutman, Rellie Gez, Vered Horwitz, Shlomit Dachir and Tamar Kadar*

Purpose: To further investigate the inflammatory response as one of the leading factors in the development of delayed limbal stem cell deficiency, clinically manifested by corneal neovascularization , following sulfur mustard ocular exposure in rabbits and to evaluate potential therapy. 

Materials and methods: Right eyes of rabbits were exposed to sulfur mustard vapor. Clinical examination was performed and the growth of corneal blood vessels was evaluated. Inflammatory cells (neutrophils, macrophages, antigen-presenting cells and T cells) were identified immunohistochemically. Tacrolimus (Prograf, Teva, 5mg/ml) an immuno-modulator drug, was tested via sub-conjunctival injection (50µl), started either before or after the development of neovascularization (72h and 4weeks, respectively) given once a week for 3weeks. 

Results: Limbal stem cell deficiency, associated with inflammatory-related corneal neovascularization was developed starting at two weeks post-exposure. The cellular inflammation included elevation of neutrophils in the limbus at one week and later (2-4weeks) in the cornea. Antigen-presenting cells (predominantly dendritic cells) were seen in the limbus and the cornea at 1-4w, together with a massive accumulation of T cells that were correlated with neovascularization score. Treatment with tacrolimus was not effective in reducing the clinical signs or inflammatory infiltration. 

Conclusions: Sulfur mustard-induced delayed limbal stem cell deficiency associated with corneal angiogenesis and inflammatory infiltration of neutrophils, dendritic cells and T cells in the limbus and cornea was observed. In spite of the association between T cells infiltration and corneal neovascularization, treatment with tacrolimus, did not reduce the inflammatory response and was not beneficial as a single drug therapy against the late sulfur mustard ocular injury.

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Published on: Dec 24, 2019 Pages: 23-30

Full Text PDF Full Text HTML DOI: 10.17352/atte.000006
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