Dexamethasone Reduces Photoreceptor Damage Caused by Photodynamic Therapy in a Rat Model of Choroidal Neovascularization
Haicheng She 1,
Toru Nakazawa 2,
Akihisa Matsubara 2,
Edward Connolly 2,
Toshio Hisatomi 2,
Kousuke Noda 2,
Ivana K. Kim 2,
Evangelos S. Gragoudas 2,
and
Joan W. Miller 2*
1 Angiogenesis and Laser Laboratories, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States; Beijing Tongren Eye Center,Beijing Tongren Hospital, Capital Medical University, Beijing, China
2 Angiogenesis and Laser Laboratories, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: jwmiller{at}meei.harvard.edu.
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Abstract |
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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 protein1(MCP-1), C-C chemokine receptor 2(CCR2), interleukin 1 beta(IL-1
) and myeloperoxidase(MPO) were performed. To study the effect of corticosteroids in combination with PDT, either dexamethasone(100mg/kg) or control was injected intraperitoneally 1 h before PDT. Animals were sacrificed 24 h 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-1 was increased in CNV lesions 24 h 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 CNV lesions. Dexamethasone-treated animals had significantly fewer TUNEL positive cells in the photoreceptor layer compared to the controls(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 to control(p<0.05).
Conclusions. Systemic administration of dexamethasone combined with PDT reduces photoreceptor apoptosis, increases angiographic closure and reduces CNV size compared to PDT alone in a rat model.
Key Words:
age-related macular degeneration, apoptosis, angiogenesis, corticosteroids, photodynamic therapy, animal model
