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Originally published In Press as doi:10.1167/iovs.07-1154 on April 17, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:5008-5014.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.07-1154
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Photoreceptor Protection after Photodynamic Therapy Using Dexamethasone in a Rat Model of Choroidal Neovascularization

Haicheng She,1,2,3 Toru Nakazawa,1,3 Akihisa Matsubara,1 Edward Connolly,1 Toshio Hisatomi,1 Kousuke Noda,1 Ivana Kim,1 Evangelos S. Gragoudas,1 and Joan W. Miller1

1From the Angiogenesis and Laser Laboratories, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; and the 2Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

PURPOSE. To study whether corticosteroids protect photoreceptors when combined with photodynamic therapy (PDT) in a laser-induced model of choroidal neovascularization (CNV).

METHODS. PDT was performed in 36 Brown-Norway rats 2 weeks after laser induction of CNV. The expressional change of several cytokines and chemokines in the CNV lesions after PDT was measured by real-time PCR in combination with laser-capture microdissection. Immunostaining for monocyte chemoattractant protein (MCP)-1, C-C chemokine receptor 2(CCR2), interleukin (IL)-1β, and myeloperoxidase(MPO) were performed. To study the effect of corticosteroids in combination with PDT, either dexamethasone (100 mg/kg) or control was injected intraperitoneally 1 hour before PDT. Animals were killed 24 hours or 1 week after PDT. CNV was examined by fluorescein angiography and choroidal flatmount. Photoreceptor degeneration was evaluated by TUNEL assay.

RESULTS. MCP-1 and IL-1β was increased in CNV lesions 24 hours after PDT. CCR2 was also expressed in laser-induced CNV but did not increase after PDT. Twenty-four hours after PDT, MPO-positive cells were noted in the CNV lesions. Dexamethasone-treated animals had significantly fewer TUNEL-positive cells in the photoreceptor layer than did the control animals (P < 0.05) after PDT. Fluorescein angiographic grading of CNV closure 6 days after PDT showed a closure rate in the dexamethasone-treated group of 31% (15/48 lesions) compared to 10% (4/42 lesions) in the control group (P < 0.05). CNV size was significantly smaller in the dexamethasone-treated group 1 week after PDT compared with the control (P < 0.05).

CONCLUSIONS. Systemic administration of dexamethasone combined with PDT reduces photoreceptor apoptosis, increases angiographic closure, and reduces CNV size compared with PDT alone in a rat model.






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