Clodronate liposome treatment contributes to the nerve regeneration in corneal nerve involvement of diabetic mice
Research article published in Experimental animals (2025)
Abstract
The dense nerve and thin vascular structure of the corneal tissue provide the refractive function in healthy eyes. Diabetes mellitus causes ocular complications including corneal opacification because of corneal nerve degeneration. Diabetic neurotrophic keratopathy is characterized by reduced corneal sensitivity, delayed corneal wound healing, and nerve degeneration. Neurotization and vascularization inhibit each other in the cornea. Macrophages contribute to the corneal neovascularization. To investigate the role of macrophage in neurotrophic keratopathy, clodronate liposome was subconjunctivally injected into diabetic db/db mice with neurotrophic keratopathy. The clodronate liposome treatment decreased F4/80+ macrophage infiltration into the corneal epithelium, and improved corneal nerve involvement in diabetic db/db mice. Furthermore, we found that Il1b and Il34 mRNA expression was increased in the corneal epithelium of clodronate-treated diabetic db/db mice. These cytokines contribute to the maintenance of nerve tissues via microglia and nerve regeneration; however, their role in corneal nerve involvement remains unknown. Notably, the intraocular injection of recombinant IL-1β and IL-34 promoted nerve regeneration in the cornea of diabetic db/db mice. These results suggest that clodronate liposome treatment contributes to nerve regeneration during corneal involvement via IL-1β and IL-34 signaling.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Peer-reviewed clinical and outcomes research relevant to medicinal leech therapy and its biology. Indexed in PubMed and verified against the NCBI record.
Why This Matters for Hirudotherapy
This study in diabetic db/db mice with neurotrophic keratopathy found that subconjunctival clodronate liposome injection depleted corneal macrophages and improved corneal nerve regeneration, an effect linked to increased IL-1beta and IL-34 signaling, with recombinant IL-1beta and IL-34 also promoting nerve regeneration. There is no hirudotherapy relevance here at all: the work concerns macrophage depletion and corneal nerve repair in a diabetes model and involves no medicinal leeches, no leech secretome, and no leech-derived anticoagulant; the slug appears to be a topical/keyword collision rather than a hirudotherapy paper. Accordingly, ASH should set expectations to none, and the honest caveat is simply that this is a preclinical mouse study outside the scope of leech therapy, with no clinical or hirudotherapy implications to draw.
Citation
Clodronate liposome treatment contributes to the nerve regeneration in corneal nerve involvement of diabetic mice.
Ueno et al. · Experimental animals, 2025
Added to ASH library: May 28, 2026 · Site last updated: June 18, 2026