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T. Baba, I. A. Bhutto, C. Merges, R. Grebe, D. S. McLeod, D. Emmert, D. Armstrong, G. A. Lutty; A Rat Model for Choroidal Neovascularization Using Subretinal Injection of Lipid Hydroperoxide. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2055.
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To develop and characterize an experimental animal model of choroidal neovascularization (CNV) that emulates CNV in wet age-related macular degeneration (AMD). The most commonly used model has a critical difference from human AMD in that it is trauma-induced. It requires a laser burn sufficient to damage Bruchs membrane (BM) and produces a wound-healing inflammatory reaction that causes CNV. Lipid hydroperoxide (LHP) is also found in BM in AMD and has been reported to generate CNV in rabbit eyes. We developed a rat CNV model using subretinal LHP as angiogenic stimulus and investigated it’s characteristics.
Sprague-Dawley rats (n=35) were used. Three weeks after a single subretinal injection of 30 µg of HpODE [13(S)-hydroperoxy-9Z, 11E-octadecadienoic acid, n=9 eyes], eyes were enucleated. HODE [13(S)-hydroxy-9Z, 11E-octadecadienoic acid, n=8] and borate buffer (n=7) were used as a negative control. Flatmount choroids were labeled with GSA-lectin, as a vascular marker, and were analyzed with a confocal microscope. Serial sections from JB4 embedded tissue were obtained for structural analysis. Follow-up fluorescein angiography in 6 eyes was carried out every week until 5 weeks after the injection.
The development of CNV was confirmed in 5 flatmount eyes (83%) of 6 HpODE injected eyes. The CNV areas, based on the confocal images, were greatest in HpODE injected eyes (av. 0.23mm2, 5/6) compared to that in HODE (av. 0.03mm2, 2/5) and borate buffer (0.02mm2, 1/4) injected eyes. Histologically, the CNV extended from choriocapillaris into the subretinal space. From angiography, the CNV presented maximum leakage at 3 to 4 weeks after injection and subsided by the 5th week.
LHP-induced CNV was highly reproducible and its natural course was ideal for evaluating therapeutic modalities. Though BM was undamaged by surgery, the CNV grew into the subretinal space and only a few inflammatory cells were recruited to the site. Since LHP has been isolated from aged BM, the LHP-induced rat CNV model seems to be a good model for human wet AMD.
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