Topically applied tacrolimus was detectable in the ipsilateral vitreal body, the plasma, and the ipsilateral trigeminal ganglion but not in their contralateral counterparts and vital organs after 4 weeks of topical release. Four weeks after denervation, rats that had received tacrolimus topically showed similar limbal innervation but a significantly higher nerve fiber density in the center of the cornea compared to the non-treated control. Trigeminal nerve ablation in rats reliably induced corneal denervation. Sensory neurons whose axons were exposed to tacrolimus regenerated significantly more and longer axons compared to vehicle-treated cultures. Biocompatibility, degradation, drug biodistribution, and therapeutic effectiveness were tested in a rat model of neurotrophic keratopathy induced by stereotactic trigeminal nerve ablation. Then, a biodegradable nanofiber drug delivery system was fabricated via electrospinning of a tacrolimus-loaded polycarbonate-urethane polymer. Axon area and length were measured after 48 hours. The regenerating axons but not the cell bodies were exposed to tacrolimus (50 ng/mL), nerve growth factor (50 ng/mL), or a vehicle control. Here, topically delivered tacrolimus is evaluated for its therapeutic potential to promote corneal reinnervation in rats.Ī compartmentalized neuronal cell culture was used to determine the effect of locally delivered tacrolimus on sensory axon regeneration in vitro. Insufficient corneal innervation can cause neurotrophic keratopathy. To sum up, DMA exhibited a potent clinical application with a cocktail of key therapeutic factors, in which PGRN was a crucial factor in promoting neurite outgrowth and re-establishing homeostasis of the cornea.Ĭorneal nerve fibers provide sensation and maintain the epithelial renewal process. Intriguingly, progranulin (PGRN), one of enriched proteins identified in DMA, was firstly recognized for its neurotrophic role in alleviation of corneal damage. Further, in order to find key components responsible for the faster recovery, high-throughput proteomic analyses were conducted and more than 2000 proteins, including associated signaling pathways, were identified in DMA. In this study we found that cornea treated with DMA showed accelerated recovery compared with those received amniotic membrane (AM) treatment by fluorescein staining, slip-lamp examination, OCT and corneal nerve immunostaining. Owing to the transparent characteristic of DMA, DMA could be applied as novel ocular bandages with nutritious function. Thus, we intended to investigate their potential application in facilitating corneal repair after alkali burn. In our previous work, decellularized matrix of adipose derived mesenchymal stromal cells (ADMSCs), named as DMA, presented excellent conjunctival repair capacity with proper suture resistance and immune modulatory characteristics. Promotion of corneal dense network of nerve is a promising method to treat severe corneal injury, yet with limited effective drugs.
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