Abstract
Corneal nerves are mainly derived from the ophthalmic branch of the trigeminal ganglion (TG). Corneal neuropathy contributes to epithelial degenerative changes in diabetic keratopathy. Efficient drug delivery to TG may be beneficial for the treatment of diabetic keratopathy. This article described intranasal delivery of nanomicelle curcumin to correct pathophysiological conditions in TG to promote corneal epithelial/nerve wound healing in streptozotocin-induced diabetic mice. A diabetic mice model with corneal epithelium abrasion was established. Ocular topical and/or intranasal nanomicelle curcumin treatments were performed, and treatment efficacy and mechanisms of action were explored. Results showed that intranasal nanomicelle curcumin treatment promoted corneal epithelial wound healing and recovery of corneal sensation. Enhanced accumulation of reactive oxygen species, reduced free radical scavengers, increased mRNA expressions of inflammatory cytokines, and decreased mRNA expressions of neurotrophic factors in the cornea and TG neuron were observed in diabetic mice with corneal epithelium abrasions. Intranasal nanomicelle curcumin treatment effectively recovered these pathophysiological conditions, especially that of the TG neuron, and a strengthened recovery was observed with ocular topical combined with intranasal treatment. These findings indicated that intranasal curcumin treatment effectively helped promote diabetic corneal epithelial/nerve wound healing. This novel treatment might be a promising strengthened therapy for diabetic keratopathy.
Highlights
Conventional methods in corneal epithelial wound repair are not just related to pain and inconvenience, and provide a window for infection that can lead to devastating and irreparable vision problems
The corneal sensitivity was significantly attenuated in diabetic mice when compared with normal mice (P < 0.01), and was further attenuated after the corneal epithelium abrasions (P < 0.01), the cornea recovered 7 days after nanomicelle curcumin treatment
Compared with the DC group, the OT group showed no significant improvement in both peripheral and central corneal nerve densities (P ≥ 0.05); the IN group and OT +IN group mice showed significant improvement, and a strengthened effect was observed in the OT +IN group (P < 0.05 when compared with the OT group; Fig. 2B). These results suggest that in diabetic mice, intranasal nanomicelle curcumin solution promotes corneal epithelial wound healing accompanied with recovery of corneal sensitivity and corneal nerve density
Summary
Conventional methods in corneal epithelial wound repair are not just related to pain and inconvenience, and provide a window for infection that can lead to devastating and irreparable vision problems. Decreased corneal innervation and sensitivity in diabetic patients leads to impaired epithelial wound healing, predisposing patients to sight-threatening complications such as stromal opacification, surface irregularity, and microbial infection. Diabetic corneal abnormalities may reflect a loss of trophic influences from the trigeminal nerve[10]. Target delivery to the trigeminal nerve may be beneficial for the treatment of the diabetic keratopathy. Studies in the past few years have shown intranasal drug delivery along the trigeminal nerve pathway. Evidence suggests that an intranasally administered drug can reach the trigeminal nerve and perineural space from the absorbent respiratory and olfactory pseudoepithelium, because they are innervated by the trigeminal nerve. Current trends in curcumin research have concentrated on the development of potential delivery systems (such as nanocarrier delivery system) to increase its aqueous solubility, stability, and bioavailability as well as delivery at or around target tissues. Polymeric nanomicelles based on a new amphiphilic polymer polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer
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