Investigating the Effect of Ciliary Body Photodyanmic Therapy in a Glaucoma Mouse Model

Abstract

Abstract: : Purpose: We have previously reported that ciliary body photodynamic therapy (PDT) significantly reduced the intraocular pressure (IOP) in normal mouse eyes. In order to determine whether ciliary body PDT may be a useful therapy in glaucoma we have investigated the morphologic and functional effects of verteporfin ciliary body PDT in a murine model of glaucoma. Methods: A glaucomatous mouse strain, DBA/2J and a normal control mouse strain (C57/BL6) animals were used in this study. The IOP was measured throughout the study using an applanation tonometer with a fiberoptic pressure sensor. Verteporfin was injected intravenously at doses of 1.0 mg/kg (DBA/2J), 2.0 or 4.0 mg/kg (C57/BL6). Transscleral irradiation of the ciliary body was performed using light at a wavelength of 689 nm delivered via 600 µm optical fiber, irradiance of 1800 mW/cm² and fluence of 100 J/cm². One eye of each animal was treated and the fellow eye served as a control. IOP was followed for 8 weeks (n=12 in DBA/2J mice, n=5 in C57/BL6 mice in each dose). The morphologic effect of PDT on the ocular structures was assessed by light and electron microscopy at 1 and 7 days and 8 weeks after PDT (n=2 in each group at each time point). Surviving retinal ganglion cells (RGC) in DBA/2J mice eyes were retrogradely labeled with fluorogold at 12 weeks after PDT. Results: The mean IOP in treated eyes was significantly reduced compared to the control eyes in all groups. The reduction of mean IOP in DBA/2J mouse eyes persisted for 7 weeks, altough the mean IOP in normal mouse eyes treated with 2 or 4 mg/kg verteporfin returned to control values by 7 and 17 days after treatment respectively. In all groups, almost all ciliary body blood vessels were thrombosed 1 day after PDT. In DBA/2J mice, ciliary epithelium and stroma were severely damaged 1 day after PDT and some ciliary body blood vessels were still thrombosed at 7 days after PDT. The mean number of RGC in the treated eyes was significantly higher than control eyes of DBA/2J mice. Conclusions: Ciliary body PDT resulted in morphological changes in the ciliary body and significant reduction of IOP in a mouse glaucoma model. These results suggest that ciliary body PDT may lead to a more selective cyclodestructive technique with potential clinical application in the treatment of glaucoma.

Keywords: ciliary body • photodynamic therapy • intraocular pressure