Abstract
Purpose :
The contribution of mast cells to ocular surface (lymph)angiogenesis has been suggested recently. Ketotifen, a H-1 receptor inhibitor and mast cell stabilizer is widely used in clinics in allergic diseases of the ocular surface. However, its effect on ocular surface neovascularization is still unknown. Herein, we assess its effect on corneal neovascularization and the modulation of immune cell populations actively participating in early-phase neovascular response in the cornea.
Methods :
The murine corneal neovascularization model was used by placing 3 figure-of-eight intrastromal sutures evenly in Balb/c mice for 2 weeks. Meanwhile, for local drug application, we applied ketotifen and PBS (control) as eye drops 3 times per day and 1 subconjunctival injection every other day. In vivo slit lamp photography was performed on days 4 and 7 to analyze corneal blood vessels. Two weeks after suturing, corneal (lymph)angiogenesis, and the mast cell distributions were quantified in whole mounts. Furthermore, neutrophils, mast cells, and macrophages that contribute to mast cell recruitment as well as to lymphangiogenesis were examined by flow cytometry on day 4 after suturing.
Results :
The administration of ketotifen significantly reduced both hemangiogenesis(p<0.05) and lymphangiogenesis (p<0.01) on day14. In vivo analysis indicated a reduction of blood vessels on day 4 and 7. During the early stage of inflammation on day 4, ketotifen treatment could reduce CD45+ lymphocyte infiltration significantly (p<0.05).
Conclusions :
Our findings suggest combined H1-inhibition and mast cell stabilisation to inhibit pathological corneal (lymph)angiogenesis. Additionally, inflammatory cell infiltration in the early stages was reduced, thus opening new treatment avenues against pathological corneal (lymph)angiogenesis.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.