Clodronate liposome treatment contributes to the nerve regeneration in corneal nerve involvement of diabetic mice.

Autor: Ueno H; Department of Immunology and Parasitology, St. Marianna University School of Medicine., Hattori T; Department of Ophthalmology, Tokyo Medical University., Chi HH; Department of Animal Models for Human Diseases, Institute of Biomedical Science, Kansai Medical University., Miyabe Y; Department of Immunology and Parasitology, St. Marianna University School of Medicine., Murayama MA; Department of Animal Models for Human Diseases, Institute of Biomedical Science, Kansai Medical University.
Jazyk: angličtina
Zdroj: Experimental animals [Exp Anim] 2024 Aug 06. Date of Electronic Publication: 2024 Aug 06.
DOI: 10.1538/expanim.24-0063
Abstrakt: 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 interleukin (IL)-1β and IL-34 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.
Databáze: MEDLINE