Photoreceptor protection after photodynamic therapy using dexamethasone in a rat model of choroidal neovascularization

Haicheng She, Toru Nakazawa, Akihisa Matsubara, Edward Connolly, Toshio Hisatomi, Kousuke Noda, Ivana Kim, Evangelos S. Gragoudas, Joan W. Miller

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)5008-5014
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number11
DOIs
Publication statusPublished - Nov 1 2008

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Choroidal Neovascularization
Photochemotherapy
Dexamethasone
Lasers
Chemokine CCL2
Chemokine Receptors
In Situ Nick-End Labeling
Interleukin-1
Peroxidase
Adrenal Cortex Hormones
C Chemokines
Laser Capture Microdissection
CC Chemokines
Photoreceptor Cells
Fluorescein Angiography
Protein C
Fluorescein
Chemokines

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Photoreceptor protection after photodynamic therapy using dexamethasone in a rat model of choroidal neovascularization. / She, Haicheng; Nakazawa, Toru; Matsubara, Akihisa; Connolly, Edward; Hisatomi, Toshio; Noda, Kousuke; Kim, Ivana; Gragoudas, Evangelos S.; Miller, Joan W.

In: Investigative Ophthalmology and Visual Science, Vol. 49, No. 11, 01.11.2008, p. 5008-5014.

Research output: Contribution to journalArticle

She, H, Nakazawa, T, Matsubara, A, Connolly, E, Hisatomi, T, Noda, K, Kim, I, Gragoudas, ES & Miller, JW 2008, 'Photoreceptor protection after photodynamic therapy using dexamethasone in a rat model of choroidal neovascularization', Investigative Ophthalmology and Visual Science, vol. 49, no. 11, pp. 5008-5014. https://doi.org/10.1167/iovs.07-1154
She, Haicheng ; Nakazawa, Toru ; Matsubara, Akihisa ; Connolly, Edward ; Hisatomi, Toshio ; Noda, Kousuke ; Kim, Ivana ; Gragoudas, Evangelos S. ; Miller, Joan W. / Photoreceptor protection after photodynamic therapy using dexamethasone in a rat model of choroidal neovascularization. In: Investigative Ophthalmology and Visual Science. 2008 ; Vol. 49, No. 11. pp. 5008-5014.
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abstract = "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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T1 - Photoreceptor protection after photodynamic therapy using dexamethasone in a rat model of choroidal neovascularization

AU - She, Haicheng

AU - Nakazawa, Toru

AU - Matsubara, Akihisa

AU - Connolly, Edward

AU - Hisatomi, Toshio

AU - Noda, Kousuke

AU - Kim, Ivana

AU - Gragoudas, Evangelos S.

AU - Miller, Joan W.

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Y1 - 2008/11/1

N2 - 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.

AB - 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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