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H. She, T. Nakazawa, A. Matsubara, T. Hisatomi, A. Hafezi–Moghadam, E.S. Gragoudas, J.W. Miller; Inhibition of Nitric Oxide Synthetase Reduces Photoreceptor Damage Caused by Photodynamic Therapy in a Model of Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4570.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of nitric oxide synthetase (NOS) in photoreceptor degeneration associated with photodynamic therapy (PDT) in a laser–induced model of choroidal neovascularization (CNV).
CNV was induced in the eyes of adult Brown–Norway rats using laser (532nm, 150mW, 100µm, 100ms). Two weeks after laser injury, PDT (689nm, 600mW/cm2, 25J/cm2, verteporfin 6mg/m2) was performed. At 6, 24, and 48h after PDT, animals were sacrificed and photoreceptor apoptosis was quantified by TdT–dUTP terminal nick–end labeling (TUNEL). To investigate the effect of NOS inhibition on PDT–induced photoreceptor apoptosis, a single dose of the NOS inhibitor N–Nitro–L–arginine methyl ester (L–NAME, 60mg/kg) or saline was injected intraperitoneally 1h before PDT. Animals were sacrificed 24h after PDT and photoreceptor apoptosis was evaluated by TUNEL.
Two weeks after laser injury, very few TUNEL (+) cells were detected in the outer nuclear layer (ONL) or in the CNV. After PDT, TUNEL (+) cells were detected both in the CNV and in the ONL of the retina overlying the CNV. The peak of photoreceptor degeneration occurred at 24h after PDT. However, 24 h after PDT, significantly fewer TUNEL (+) cells were found in the ONL of lesions of the L–NAME treated animals (0.7±1.1, n=16 lesions) when compared to those of the saline treated animals (13.9±8.4, n=11 lesions, p< 0.05).
Our preliminary data suggest that NOS inhibition may reduce PDT–induced photoreceptor degeneration in an experimental model of CNV in rats. Adjunctive NOS inhibition may have neuroprotective benefits in reducing photoreceptor injury after PDT.
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