Immunocytochemical localization of vascular endothelial growth factor in neurons and glial cells of human retina.

In order to establish the cellular and subcellular localization of the chemokine protein, vascular endothelial growth factor (VEGF) or vascular permeability factor, in adult human retina, we employed immunocytochemistry with double immunolabeling, using a primary antibody to amino acids 1-10 of VEGF, together with antibodies to vimentin (intermediate filaments, labeling Müller cells) or to neuron-specific enolase (labeling retinal neurons). In adult human retina, VEGF-like immunoreactivity (VEGF-IR) is found in Müller cell processes, where typically it is found in the cytoplasm in close association with Vimentin-labeled (VM-IR) intermediate filaments. VEGF-IR is sometimes found diffusely in Müller cell bodies and nuclei. VEGF-IR is found in all major classes of retinal neurons, as demonstrated by co-localization with neuron-specific enolase (NSE)-IR, but is especially prominent in cell bodies of amacrine cells (ACs) (including displaced ACs) and ganglion cells (GCs). Generally, VEGF-IR is more prominent in the nucleus, while NSE-IR is more prominent in the cytoplasm and neurites. In blood vessels, VEGF-IR co-localizes with VM-IR, marking blood vessel endothelial cells, whereas NSE-IR apparently marks the layer of smooth muscle cells. These cellular findings regarding the retinal localization of VEGF-IR are consistent with VEGF synthesis in and its export from retinal neurons, particularly amacrine and ganglion cells, as well as in glia, specifically Müller cells, and suggest that retinal neurons normally provide continuous trophic support for their retinal blood supply.