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D. G. Espinosa-Heidmann, G. Malek, P. Saloupis, F. Wu, K. G. Csaky, S. W. Cousins; The Effect of Sstemic Exposure to Inflammatory Stimuli on Neurosensory Retinal Degeneration Associated With Experimental Choroidal Neovascularization (CNV). Invest. Ophthalmol. Vis. Sci. 2008;49(13):5162.
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CNV in age-related macular degeneration (AMD) is associated with infiltration of macrophages into the CNV and overlying neurosesnory retina where they presumably secrete inflammatory molecules (i.e, TNFα) and angiogenic factors. Retinal dysfunction and outer retinal morphologic disruption is also observed in the retina overlying CNV Additionally intravitreal injections of TNFα results in retinal dysfunction in the absence of overt retinal morphological changes. In this study we evaluated whether macrophages contribute to the morphological disruption seen in the retina overlying laser induced CNV in mice treated with triamcinolone and the macrophage activator (TSST-1).
Laser CNV was induced in twenty four C57BL/6 female mice aged 8-9 months using a diode red laser (810 nm), and were divided into one of 4 groups (n=5-6/group). Group 1 and 2: PBS or 1.2 mg of triamcinolone was injected subconjunctivally 5 days after laser.; Group 3 and 4: 10µg of TSST-1 was injected intraperitoneally, 5 days later 1.2 mg of triamcinolone or PBS was injected sub-conjunctivally. Mice were euthanized at approximately day 17 post-laser induced CNV. Eyes were collected and processed for electron microscopy and immunohistochemistical staining with macrophage markers F4/80 and Iba-1, retinal markers SV2, GLAST, pERK and c-fos.
As shown previously, CNV was associated with significant macrophage infiltration and outer retinal degeneration overlying the neovascularization. The changes were more pronounced in mice receiving systemic exposure to TSST, a macrophage activator. CNV size was significantly smaller in mice treated with triamcinolone five days after laser, and steroid treatment was associated with significantly decreased F4/80 and Iba-1 immunopositive macrophages in both CNV and retina. However, outer retinal disruption and abnormal distribution of synaptic markers (SV2 immunoreactivity) was relatively unaffected by triamcinolone treatment.
As expected steroid administration decreased the number of inflammatory macrophages and size and severity of CNV. However, it did not alter the outer retinal morphology. Although macrophage-derived factors can cause abnormal retinal function in the setting of normal retinal morphology, the mechanisms of profound retinal morphological disruption in laser CNV model may not be caused by macrophage infiltration.
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