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2018 ; 24
(ä): 274-285
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Resolvin D1 promotes corneal epithelial wound healing and restoration of
mechanical sensation in diabetic mice
#MMPMID29643724
Zhang Z
; Hu X
; Qi X
; Di G
; Zhang Y
; Wang Q
; Zhou Q
Mol Vis
2018[]; 24
(ä): 274-285
PMID29643724
show ga
PURPOSE: To investigate the effect and mechanism of proresolving lipid mediator
resolvin D1 (RvD1) on the corneal epithelium and the restoration of mechanical
sensation in diabetic mice. METHODS: Type 1 diabetes was induced in mice with
intraperitoneal streptozocin injections. The healthy and diabetic mice underwent
removal of the central corneal epithelium, and then 100 ng/ml RvD1 or its formyl
peptide receptor 2 (FPR2) antagonist WRW4 was used to treat the diabetic mice.
Regeneration of the corneal epithelium and nerves was observed with sodium
fluorescein staining and whole-mount anti-?3-tubulin fluorescence staining. The
inflammatory response level was measured with hematoxylin and eosin staining
(inflammatory cell infiltration), enzyme-linked immunosorbent assay (tumor
necrosis factor alpha and interleukin-1 beta content), myeloperoxidase activity,
and fluorescence staining (macrophage content). The reactive oxygen species (ROS)
and glutathione (GSH) levels were examined with incubation with fluorescent
probes, and oxidative stress-related protein expression levels were evaluated
with fluorescence staining and western blotting. RESULTS: Topical application of
RvD1 promoted regeneration of the corneal epithelium in diabetic mice,
accompanied by the reactivation of signaling and inflammation resolution related
to regeneration of the epithelium. Furthermore, RvD1 directly attenuated the
accumulation of ROS and nicotinamide adenine dinucleotide phosphate oxidase 2/4
expression, while RvD1 enhanced GSH synthesis and reactivated the Nrf2-ARE
signaling pathway that was impaired in the corneal epithelium in the diabetic
mice. More interestingly, topical application of RvD1 promoted regeneration of
corneal nerves and completely restored impaired mechanical sensitivity of the
cornea in diabetic mice. In addition, the promotion of corneal epithelial wound
healing by RvD1 in diabetic mice was abolished by its FPR2 antagonist WRW4.
CONCLUSIONS: Topical application of RvD1 promotes corneal epithelial wound
healing and the restoration of mechanical sensation in diabetic mice, which may
be related to the lipid mediator's regulation of inflammation resolution, the
reactivation of regenerative signaling in the epithelium, and the attenuation of
oxidative stress.