A Mouse Model for Laser-induced Choroidal Neovascularization

Abstract

The mouse laser-induced choroidal neovascularization (CNV) model has been a crucial mainstay model for neovascular age-related macular degeneration (AMD) research. By administering targeted laser injury to the RPE and Bruch's membrane, the procedure induces angiogenesis, modeling the hallmark pathology observed in neovascular AMD. First developed in non-human primates, the laser-induced CNV model has come to be implemented into many other species, the most recent of which being the mouse. Mouse experiments are advantageously more cost-effective, experiments can be executed on a much faster timeline, and they allow the use of various transgenic models. The miniature size of the mouse eye, however, poses a particular challenge when performing the procedure. Manipulation of the eye to visualize the retina requires practice of fine dexterity skills as well as simultaneous hand-eye-foot coordination to operate the laser. However, once mastered, the model can be applied to study many aspects of neovascular AMD such as molecular mechanisms, the effect of genetic manipulations, and drug treatment effects. The laser-induced CNV model, though useful, is not a perfect model of the disease. The wild-type mouse eye is otherwise healthy, and the chorio-retinal environment does not mimic the pathologic changes in human AMD. Furthermore, injury-induced angiogenesis does not reflect the same pathways as angiogenesis occurring in an age-related and chronic disease state as in AMD. Despite its shortcomings, the laser-induced CNV model is one of the best methods currently available to study the debilitating pathology of neovascular AMD. Its implementation has led to a deeper understanding of the pathogenesis of AMD, as well as contributing to the development of many of the AMD therapies currently available.

The Urokinase Receptor-Derived Peptide UPARANT Mitigates Angiogenesis in a Mouse Model of Laser-Induced Choroidal Neovascularization

“…23,24 The laser-induced CNV model is one of the best models currently used to mimic the pathologic mechanisms in nAMD, although some differences in the chorioretinal environment and in the disease state (acute versus chronic) have been evidenced between mice and humans. 25 In the mouse model, we evaluated the effectiveness of UPARANT in inhibiting laser-induced CNV. In addition, we evaluated uPAR pathway involvement in CNV and whether the effects of UPARANT are mediated through the uPA/uPAR system.…”

Pirfenidone ameliorates the formation of choroidal neovascularization in mice

“…It is proposed that intravenous injection should be carried out to assess the clinical application of the drug. This study used the laser-induced CNV model, which has been shown to be repeatable and stable (26). However, there are a number of limitations of the present study.…”

“…Mice in the normal group (n=9) were not induced. Following mydriasis, the mice were placed on a platform under the slit lamp and a laser-induced CNV model was established due to rupture of the Brunch's membrane, as previously described (26). Laser photocoagulation (532-nm laser, 200-mW, 100-ms duration, 50-µm spot size) was performed bilaterally in each mouse.…”

Discovery of novel L-type voltage-gated calcium channel blockers and application for the prevention of inflammation and angiogenesis

“…We further evaluated the capacity of the substance to alter the electric potential of BV-2 cells. The substance with the highest binding energy to L-VGCC was evaluated in vivo using two clinically relevant animal models: mouse laser-induced neovascularization (CNV) [13] and suture-induced inflammatory corneal neovascularization (SI-CNV) in rats [14][15][16]. We used these models to evaluate the therapeutic potential of the designed compounds to inhibit pathological angiogenesis by targeting the activation and migration of inflammatory cells.…”