The Role of the Extracellular Matrix in Regulating Corneal Angiogenesis and Lymphangiogenesis

Blood and lymphatic vessels are present in nearly all mammalian tissues. They regulate vital metabolic processes, with their roles beginning early in embryogenesis. Blood vessels supply virtually all cells with oxygen and nutrients, while lymphatic vessels work in conjunction by draining interstitial fluid, allow for the absorption of fats and fat-soluble vitamins, and provide a pathway for immune cell trafficking. Due to the difficulty in visualization and study of lymphatic vasculature, progress in the study of lymphangiogenesis has stalled in comparison to angiogenesis. Limbal stem cells (LSCs) are present in the limbus, which aid in the renewal of the corneal epithelium. The blood vessels and lymphatic vessels that are present within the limbal region of the cornea arise from the anterior ciliary arteries and lymphatic vessels. Inflammatory stimuli can trigger the ingrowth of blood vessels and lymphatic vessels into the cornea, which leads to a loss of the immune privilege and transparency of the cornea. While the mechanisms of corneal neovascularization are not fully understood, infections, immune diseases, and diseases associated with a deficiency in limbal cells are the most common reason for significant vascularization of the cornea. This vessel formation is mediated primarily by the vascular endothelial growth factor (VEGF) family, much like other tissues, with CD44 playing an important role in pathological angiogenesis. Research into the mechanisms of vessel invagination could provide insight into treatment options as well as preventative measures against the most common causes of corneal scarring secondary to angiogenesis and lymphangiogenesis.