EFFICACY of CELL-BASED PLASMACYTOID DENDRITIC CELL THERAPY FOR CORNEAL WOUND HEALING

Abstract

Purpose : We have recently shown that plasmacytoid dendritic cells (pDCs) play a significant role in corneal homeostasis. The current study aims to determine the efficacy and safety of local adoptive transfer of pDCs for the treatment of corneal epithelial wounds.

Methods : Splenic pDCs from 6-8-week-old wild-type (WT) C57BL/6 or DPE-GFP×RAG1^-/- mice, receiving FLT3L-secreting B16 melanoma cells to enhance pDC density, were isolated by flow cytometric sorting. Central corneal epithelial debridement using a 2 mm trephine was performed on WT mice to assess the density of labelled pDCs. Epithelial debridement of central corneas was performed on PSGL-1 KO mice using a 1.5 mm trephine in order to assess the effect of pDC therapy on corneal wounds, ruling out the effect of infiltrating cells. Mice received topical fibrin sealant (sham-transfer) or 10,000 splenic pDCs. Corneal fluorescein staining was conducted 24, 48, and 72 hours after the procedure to assess wound healing. Wound areas were measured using ImageJ. Corneal would-mounts were imaged on day 2, 5, 7, and 14 after the adoptive transfer to measure the density of transferred cells. T test was used to determine differences and p<0.05 was considered significant.

Results : Adoptive transfer did not result in corneal opacity or neovascularization. Adoptively-transferred GFP⁺ pDCs were observed in the central cornea on day 2 and remained in the cornea 14 days following adoptive transfer, although in reduced numbers compared to day 2 (p<0.05). We observed that one-time adoptive transfer of pDCs significantly decreased epithelial defect size by 1.7-, 3.0- and 6.1-fold, at 24, 48, and 72 hour following corneal epithelial wounding, as compared to sham-transfer (p<0.05).

Conclusions : Local adoptive transfer of pDCs is a safe procedure, which significantly improves corneal wound healing.

This is a 2021 ARVO Annual Meeting abstract.