HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by She, H. Articles by Miller, J. W. Search for Related Content PubMed PubMed Citation Articles by She, H. Articles by Miller, J. W.

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

¹From the Angiogenesis and Laser Laboratories, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; and the ²Jules Stein Eye Institute, University of California, Los Angeles, California.

PURPOSE. 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).

METHODS. 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.

RESULTS. 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.

CONCLUSIONS. 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.

This article has been cited by other articles:

				H. She, T. Nakazawa, A. Matsubara, E. Connolly, T. Hisatomi, K. Noda, I. Kim, E. S. Gragoudas, and J. W. Miller Photoreceptor Protection after Photodynamic Therapy Using Dexamethasone in a Rat Model of Choroidal Neovascularization Invest. Ophthalmol. Vis. Sci., November 1, 2008; 49(11): 5008 - 5014. [Abstract] [Full Text] [PDF]

				R. B. Bhisitkul, B. J. Winn, O.-T. Lee, J. Wong, D. d. S. Pereira, T. C. Porco, X. He, P. Hahn, and J. L. Dunaief Neuroprotective Effect of Intravitreal Triamcinolone Acetonide against Photoreceptor Apoptosis in a Rabbit Model of Subretinal Hemorrhage Invest. Ophthalmol. Vis. Sci., September 1, 2008; 49(9): 4071 - 4077. [Abstract] [Full Text] [PDF]

				K. Noda, H. She, T. Nakazawa, T. Hisatomi, S. Nakao, L. Almulki, S. Zandi, S. Miyahara, Y. Ito, K. L. Thomas, et al. Vascular adhesion protein-1 blockade suppresses choroidal neovascularization FASEB J, August 1, 2008; 22(8): 2928 - 2935. [Abstract] [Full Text] [PDF]