A new animal model of choroidal neovascularization

Abstract

ABSTRACT.Purpose: The purpose of this study was to evaluate the ability of different methods to induce choroidal neovascularization (CNV) in the domestic pig. Methods: A total of 26 Danish landrace pigs was used. A sample of 22 eyes in 12 pigs underwent retinal photocoagulation with a xenon lamp, six eyes in four pigs underwent retinal photocoagulation with a diode laser, and mechanical rupture of Bruch's membrane (BM) was induced in 12 pigs following surgical debridement of the retinal pigment epithelium without damage to the neuroretina. Results: All 12 pigs (100%) in the group with mechanical rupture of BM developed CNV. The induced membranes were morphologically similar to CNV membranes in humans. Induced CNV was found in 13 of 22 (54%) xenon lamp-treated animals and in five of six (83%) diode laser-treated animals. The CNV in these groups was small and the morphology of the induced lesions was dominated by retinal gliosis and retinal neovascularization, probably due to a marked destruction of the neuroretina. Conclusions: Surgical debridement of the retinal pigment epithelium followed by mechanical rupture of BM is a reproducible method of producing CNV in the domestic pig, whereas photocoagulation gives rise to glially derived subretinal fibrovascular membranes and primarily retinal neovascularization.

Advanced Clinical Imaging and Tissue-based Biomarkers of the Eye for Toxicology Studies in Minipigs

“…However, as anti-Iba1 equally stains macrophages and microglial cells, this marker appears to be of limited diagnostic utility in distinguishing these 2 cell types in the inflamed retina. In light of the increasing need for novel ocular therapies targeting VEGF or other VEGF-related modulators of angiogenesis (Penn et al 2008), and the possible use of minipigs as animal model for CNV (Kiilgaard et al 2005;Lassota et al 2008), there is a demand for assessment of VEGF-target knockdown in ocular efficacy or toxicology studies. We were not aware of established ISH methods for the detection of these targets in DFfixed porcine eyes, thus we established selected mRNA-ISH methods to detect VEGFA, ANGPT2, and TEK mRNA in DF-fixed paraffin-embedded minipig eyes of the present study.…”

“…In an attempt to reduce the use of nonhuman primates, we increasingly consider Göttingen minipigs for regulatory toxicology studies, including investigation of ocular drug delivery routes. In addition, the minipig is an interesting species in ocular research translatable to human disease conditions, such as glaucoma (Dan et al 2008;Galdos et al 2012;Ruiz-Ederra et al 2005), retinitis pigmentosa (Ross et al 2012), proliferative vitreoretinopathy (Umazume et al 2012), choroidal neovascularization (CNV; Kiilgaard et al 2005;Lassota et al 2008), retinal degeneration (Huang et al 2000) or detachment (Iandiev et al 2006), in transplantation studies (Klassen et al 2008), and as a model for selective retinal capillary closure in diabetic retinopathy (Foulds et al 2010).…”

Surgical induction of choroidal neovascularization in a porcine model

“…To develop such a model in a human size eye we have previously studied the effect of surgical RPE removal followed by perforation of Bruch's membrane in porcine eyes [17,20]. This model proved itself to be suboptimal because the resulting CNV failed to exhibit leakage on fluorescein angiographic examination.…”

“…Animal models could provide us with data about the earliest phases of CNV development. So far the preferred way of CNV induction in different treatment trials has been by laser [16,31] but this method also causes retinal tissue destruction [5,17,24] which makes it complicated to determine whether damage to the neuroretina is caused by the process of CNV formation or by the laser burn. Reliable animal models with a bearing to human clinic are also essential in order to test the effect of new treatment modalities such as antiangiogenic therapy.…”

Development of Laser-Induced Choroidal Neovascularization in Rats after Retinal Damage by Sodium Iodate Injection

“…Diode laser burns can induce a choroidal neovascular process similar to other lasers [15][16][17] . When SI was administered 48 h after laser photocoagulation, the incidence of CNV 1 week later was higher (31%) than in cases in which only laser was applied (3.6%).…”