Why is the cornea avascular and how is this achieved developmentally?

• A. The cornea remains avascular due to an anti-angiogenic environment and regulatory factors during development
• B. It becomes vascularized by the conjunctival vessels and then regresses
• C. Blood vessels are excluded by the sclera
• D. Corneal nerves penetrate vessels to prevent angiogenesis

Answer: (A)

Maintaining a clear cornea requires that it stay avascular, so light can pass through without scattering. This avascular state is actively produced during development. The corneal epithelium and stroma release anti-angiogenic factors and establish a non-permissive extracellular environment that blocks blood vessel ingrowth from surrounding conjunctival and limbal vessels. In essence, the developing cornea creates a local environment that counteracts pro-angiogenic signals (for example, VEGF-driven growth) with inhibitors such as PEDF, thrombospondin-1, and other regulatory molecules. As a result, vessels from the conjunctiva do not invade the cornea, while nutrients reach corneal cells by diffusion from the tear film and aqueous humor. Corneal nerves are present for innervation and trophic support, but they do not promote vascularization.