Sustained Release of Tacrolimus From a Topical Drug Delivery System Promotes Corneal Reinnervation

dc.contributor.authorDaeschler, Simeon C.
dc.contributor.authorMirmoeini, Kaveh
dc.contributor.authorGordon, Tessa
dc.contributor.authorChan, Katelyn
dc.contributor.authorZhang, Jennifer
dc.contributor.authorAli, Asim
dc.contributor.authorFeinberg, Konstantin
dc.contributor.authorBorschel, Gregory H.
dc.contributor.departmentSurgery, School of Medicine
dc.date.accessioned2023-08-07T12:55:47Z
dc.date.available2023-08-07T12:55:47Z
dc.date.issued2022
dc.description.abstractPurpose: Corneal nerve fibers provide sensation and maintain the epithelial renewal process. Insufficient corneal innervation can cause neurotrophic keratopathy. Here, topically delivered tacrolimus is evaluated for its therapeutic potential to promote corneal reinnervation in rats. Methods: A compartmentalized neuronal cell culture was used to determine the effect of locally delivered tacrolimus on sensory axon regeneration in vitro. 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. Axon area and length were measured after 48 hours. Then, a biodegradable nanofiber drug delivery system was fabricated via electrospinning of a tacrolimus-loaded polycarbonate-urethane polymer. Biocompatibility, degradation, drug biodistribution, and therapeutic effectiveness were tested in a rat model of neurotrophic keratopathy induced by stereotactic trigeminal nerve ablation. Results: Sensory neurons whose axons were exposed to tacrolimus regenerated significantly more and longer axons compared to vehicle-treated cultures. Trigeminal nerve ablation in rats reliably induced corneal denervation. 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. 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. Conclusions: Locally delivered tacrolimus promotes axonal regeneration in vitro and corneal reinnervation in vivo with minimal systemic drug exposure. Translational relevance: Topically applied tacrolimus may provide a readily translatable approach to promote corneal reinnervation.
dc.eprint.versionFinal published version
dc.identifier.citationDaeschler SC, Mirmoeini K, Gordon T, et al. Sustained Release of Tacrolimus From a Topical Drug Delivery System Promotes Corneal Reinnervation. Transl Vis Sci Technol. 2022;11(8):20. doi:10.1167/tvst.11.8.20
dc.identifier.urihttps://hdl.handle.net/1805/34781
dc.language.isoen_US
dc.publisherAssociation for Research in Vision and Ophthalmology (ARVO)
dc.relation.isversionof10.1167/tvst.11.8.20
dc.relation.journalTranslational Vision Science & Technology
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.sourcePMC
dc.subjectCornea
dc.subjectCorneal innervation
dc.subjectNeurotrophic keratopathy
dc.subjectTopical therapeutics
dc.subjectDrug delivery
dc.subjectTacrolimus
dc.subjectFK506
dc.subjectDry eye
dc.subjectNeurotrophic keratitits
dc.subjectCorneal ulcer
dc.titleSustained Release of Tacrolimus From a Topical Drug Delivery System Promotes Corneal Reinnervation
dc.typeArticle
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