Reduced Photoreceptor Damage after Photodynamic Therapy through Blockade of Nitric Oxide Synthase in a Model of Choroidal Neovascularization

To investigate the role of nitric oxide synthase (NOS) in photoreceptor degeneration associated with photodynamic therapy (PDT) in a laser-induced model of choroidal neovascularization (CNV). PDT was performed in monkey and Brown Norway rats with laser-induced CNV. L-NAME, a NOS inhibitor, or saline...

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Published in:	Investigative ophthalmology & visual science 2007-05, Vol.48 (5), p.2268-2277
Main Authors:	She, Haicheng, Nakazawa, Toru, Matsubara, Akihisa, Hisatomi, Toshio, Young, Tara A, Michaud, Norman, Connolly, Edward, Hafezi-Moghadam, Ali, Gragoudas, Evangelos S, Miller, Joan W
Format:	Article
Language:	eng
Subjects:	Animals Apoptosis Biological and medical sciences Caspase 3 - metabolism Choroidal Neovascularization - drug therapy Choroidal Neovascularization - enzymology Choroidal Neovascularization - pathology Disease Models, Animal Diseases of the skin. Cosmetics Enzyme Inhibitors - pharmacology Eye and associated structures. Visual pathways and centers. Vision Fluorescein Angiography Fluorescent Antibody Technique, Indirect Fundamental and applied biological sciences. Psychology In Situ Nick-End Labeling Injections, Intraperitoneal Macaca fascicularis Macrophages - enzymology Medical sciences NG-Nitroarginine Methyl Ester - pharmacology Nitric Oxide Donors - pharmacology Nitric Oxide Synthase Type II - antagonists & inhibitors Photochemotherapy Photoreceptor Cells, Vertebrate - enzymology Photoreceptor Cells, Vertebrate - ultrastructure Photosensitizing Agents - therapeutic use Porphyrins - therapeutic use Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) Rats Rats, Inbred BN Retinal Degeneration - chemically induced Retinal Degeneration - enzymology Retinal Degeneration - pathology Retinal Degeneration - prevention & control Vertebrates: nervous system and sense organs
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Summary:	To investigate the role of nitric oxide synthase (NOS) in photoreceptor degeneration associated with photodynamic therapy (PDT) in a laser-induced model of choroidal neovascularization (CNV). PDT was performed in monkey and Brown Norway rats with laser-induced CNV. L-NAME, a NOS inhibitor, or saline was injected intraperitoneally in rats with CNV. An NO donor, or saline, was injected intravitreously into normal rats. Photoreceptor apoptosis was evaluated by TUNEL and electron microscopy. NOS, ED-1, and cleaved-caspase-3 (c-casp-3) expression were determined by immunohistochemistry. CNV lesions were examined by fluorescence angiography and choroidal flat mount. TUNEL and electron microscopy showed photoreceptor apoptosis after PDT. In rats, there were significantly more TUNEL-positive cells in the photoreceptors 24 hours after PDT, whereas in the CNV lesions there were more TUNEL-positive cells 6 hours after PDT. C-casp-3 was detected in the CNV lesions but not in the photoreceptors after PDT. There was no difference in the numbers of ED-1-positive macrophages before and after PDT. However, inducible NOS (iNOS) was increased after PDT in macrophages. Intravitreous injection of the NO donor without PDT also induced substantial photoreceptor apoptosis. L-NAME-treated animals had significantly fewer TUNEL-positive cells in the photoreceptors than saline-treated animals after PDT (P < 0.05). There were no differences in CNV size and leakage between L-NAME- and saline-treated groups. iNOS expression in macrophages contributes to PDT-induced photoreceptor degeneration. NOS inhibition reduces PDT-induced photoreceptor degeneration without compromising the treatment effect of PDT in an experimental model of CNV.
ISSN:	0146-0404 1552-5783 1552-5783