gms | German Medical Science

Vascularisation of the retina during development occurs as a highly organized process that is mediated by ischemia. The growing retina produces a physiologic hypoxia that induces astrocytes to migrate and to form a network on the retinal surface. In parallel hypoxia initiates the secretion of VEGF that activates the vascular endothelial cells near the optic nerve head to migrate towards the retinal periphery. This results in the formation of a vascular network that is organized as a layer within the inner retina.

In the adult retina, however, pathologic ischemia is not able to initiate regeneration of the original vascular structure. Although hypoxia induced growth factors like VEGF are secreted, the proliferating neovessels leave the retina and grow into the vitreous. Moreover, vascular differentiation is insufficient resulting in leaky vessels without the properties of a blood retinal barrier. Oxygen sensitive factors like VEGF and Angiopoietin 2 have been shown to be upregulated, whereas antagonists like Angiopoietin 1 are downregulated in the ischemic retina. These signals move the angiogenic balance towards vessel destabilization and angiogenesis.

Diseases like diabetic retinopathy or retinopathy of prematurity can initiate a neovascular response that finaly results in secondary tractional retinal detachment or neovascular glaucoma. Elevated levels VEGF could be demonstrated in the vitreous of patients with diabetic retinopathy. Therefore, inhibition of angiogenic signals might be a therapeutic option to stop the neovascular response.