Corneal neovascularization (NV) refers to the growth of blood vessels and/or lymphatics into the physiologically avascular cornea, which occurs in several pathological processes. In mouse models, corneal NV can be artificially induced to investigate mechanisms of corneal pathologies. However, mouse models of corneal NV are not restricted to cornea-specific research, but also are widely used to investigate general mechanisms of angiogenesis. Because the cornea is transparent and easily accessible, corneal NV models are among the most useful in vivo models in angiogenesis research.

The three different approaches that are used to study corneal NV in mice are based on direct application of proangiogenic or antiangiogenic transmitters, external injury to the cornea, or genetically engineered mice, which spontaneously develop corneal NV. The aim of this review is to compare the scope and limitations of the different approaches for corneal NV in mice. Our main focus is to highlight the potential of transgenic spontaneous models of corneal NV. Transgenic models do not require any experimental interference and make it possible to investigate different interconnected proangiogenic signaling cascades. As a result, transgenic models are highly useful for disease-centered angiogenesis research.

In summary, transgenic models of corneal NV will complement and advance existing ocular NV assays, and help to discover new angiogenesis-related treatment strategies for ocular and extraocular diseases.