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Corneal Neovascularization as a Target for Nucleotide-Based Therapies

Yi-Jen Hsueh, Hung-Chi Chen, Jui-Yang Lai, Jan-Kan Chen, and David Hui-Kang Ma

The cornea is a transparent tissue with avascular characteristics (corneal avascularity). It can be compromised by imbalances of angiogenic factors due to chemical injuries, infections, or autoimmune diseases such as Stevens- Johnson’s syndrome, which can lead to corneal blindness. Clinically, the etiologies of corneal neovascularization (NV), such as inflammation, immune rejection, limbal stem cell deficiency, or hypoxia, are usually long-lasting; therefore, conventional treatment modalities, including antiangiogenic medications, laser, or surgeries have only a suboptimal effect, and the prognosis is even worse with multiple recurrences. In contrast, novel treatment modalities, such as gene therapy (enhanced intracellular expression of antiangiogenic factors) and nucleotide-based antiangiogenic therapy (antisense oligonucleotides, silence-RNA, and micro-RNA) have been accomplished in animal models or clinical trials in recent years. Because of its specific and long-lasting effect, as well as the improvement and verification of the safety of expression vectors and carriers, the clinical value of nucleotide-based therapy has been increasingly appreciated. This review summarizes and updates relevant research, and provides a better understanding regarding the mechanism and treatment of corneal NV.