Abstract
Purpose:
Corneal lymphangiogenesis is one of the main risk-factors for immune mediated allograft rejection after corneal transplantation. Whereas topical VEGF inhibitors can decrease pathological neovascularization, regression of existing pathological blood and lymph vessels in the cornea remains an unsolved problem. Verteporfin photodynamic therapy (PDT) is an established treatment for subfoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). This experiment shows for the first time the effect of photodynamic ablation of lymphatic vessels in the cornea.
Methods:
Ten female BALB/c mice (aged 6-8 weeks) were used in the mouse model for suture induced inflammatory corneal neovascularization. After two weeks the treatment group (n=5) received an injection of 2.5µl Verteporfin (2mg/ml) into the corneal stroma. Control mice (n=5) received an intrastromal injection of 2.5µl PBS. After a two-hour dispersion, we performed PDT in all ten mice (t = 40s, P = 46mW). Corneas were excised 20 hours later and corneal wholemounts were stained with CD31 and LYVE-1 to detect blood and lymphatic vessels. Hemangiogenesis and lymphangiogenesis were analyzed morphometrically by using a semiautomatic method based on the image analyzing program Cell^F.
Results:
Blood vessels were reduced to 78% and lymphatic vessels dropped to 38% after PDT in the group treated with Verteporfin compared to control mice.
Conclusions:
Corneal PDT can be used to relatively selectively and specifically reduce lymphangiogenesis in the cornea. Future studies using this new technique can investigate the role of lymph vessels in graft rejection more in detail. In the clinic, this is a promising new preoperative technique to “precondition” high-risk corneas prior to transplantation to reduce allograft rejection in high-risk patients.
Keywords: 480 cornea: basic science •
609 neovascularization •
647 photodynamic therapy