Investigating the effect of ciliary body photodynamic therapy in a glaucoma mouse model.
OBJECTIVE
To investigate the morphologic and functional effects of verteporfin ciliary body photodynamic therapy (PDT) in a murine glaucoma model and normal mouse eyes.


METHODS
A glaucomatous mouse strain, DBA/2J and a normal control mouse strain (C57BL/6) were used in the study. Verteporfin was injected intravenously at doses of 1.0 (DBA/2J) or 2.0 or 4.0 (C57BL/6) mg/kg. Transscleral irradiation of the ciliary body was performed with light at a wavelength of 689 nm delivered through an optical fiber, with irradiance of 1800 mW/cm2 and fluence of 100 J/cm2. Laser irradiation was applied for 360 degrees of the corneoscleral limbus in C57BL/6 normal mice and for 180 degrees in DBA/2J mice. Retreatment was performed in C57BL/6 normal mice that had been treated with 2.0 mg/kg of verteporfin at post-PDT day 7. One eye of each animal was treated, and the fellow eye served as the control. The morphologic effect of PDT on the ocular structures was assessed by light and electron microscopy. The IOP was measured using an applanation tonometer with a fiber-optic pressure sensor. Surviving retinal ganglion cells (RGCs) in DBA/2J mice eyes were retrogradely labeled with a neurotracer dye at 12 weeks after PDT.


RESULTS
In all groups, almost all ciliary body blood vessels in the treated area were thrombosed 1 day after PDT. In DBA/2J mice, ciliary epithelium and stroma were severely damaged 1 day after PDT. The mean IOP in treated eyes was significantly reduced compared with that in the control eyes in all groups. The reduction of mean IOP in DBA/2J mouse eyes persisted for 7 weeks, although the mean IOP in normal mouse eyes treated with 2 or 4.0 mg/kg verteporfin returned to the level of the fellow control eyes by 7 and 17 days after treatment, respectively. The mean number of RGCs in the DBA/2J treated eyes was significantly higher than in control eyes.


CONCLUSIONS
Ciliary body PDT resulted in morphologic changes in the ciliary body, significant reduction of IOP, and prevention of ganglion cell loss in a mouse glaucoma model. These results suggest that ciliary body PDT is a more selective cyclodestructive technique with potential clinical application in the treatment of glaucoma.
Matsubara
Akihisa
A
Angiogenesis and Laser Laboratories, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA.
Nakazawa
Toru
T
Husain
Deeba
D
Iliaki
Eirini
E
Connolly
Edward
E
Michaud
Norman A
NA
Gragoudas
Evangelos S
ES
Miller
Joan W
JW
D000818:Animals; D002452:Cell Count; D002924:Ciliary Body / Q000098:blood supply / Q000187:drug effects* / Q000648:ultrastructure; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007429:Intraocular Pressure; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011166:Porphyrins / Q000627:therapeutic use; D012165:Retinal Ganglion Cells / Q000473:pathology; D014065:Tonometry, Ocular; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000077362:Verteporfin
D017319:Photosensitizing Agents; D011166:Porphyrins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000077362:Verteporfin