Photoreceptor protection after photodynamic therapy using dexamethasone in a rat model of choroidal neovascularization.
OBJECTIVE
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)-1beta, 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-1beta 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.
She
Haicheng
H
Department of Ophthalmology, Angiogenesis and Laser Laboratories, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114, Massachusetts, USA.
Nakazawa
Toru
T
Matsubara
Akihisa
A
Connolly
Edward
E
Hisatomi
Toshio
T
Noda
Kousuke
K
Kim
Ivana
I
Gragoudas
Evangelos S
ES
Miller
Joan W
JW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D010778:Photochemotherapy / Q000379:methods*; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017319:Photosensitizing Agents / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011166:Porphyrins / Q000627:therapeutic use*; D012313:RNA / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D054390:Receptors, CCR2 / Q000096:biosynthesis / Q000235:genetics; D016896:Treatment Outcome; D000077362:Verteporfin
C515336:Ccr2 protein, rat; D018932:Chemokine CCL2; D005938:Glucocorticoids; D016209:Interleukin-8; D017319:Photosensitizing Agents; D011166:Porphyrins; D054390:Receptors, CCR2; D000077362:Verteporfin; D012313:RNA; D003907:Dexamethasone