A model system for the study of human retinal angiogenesis: activation of monocytes and endothelial cells and the association with the expression of the monocarboxylate transporter type 1 (MCT-1)

Aims/hypothesis. The growth of retinal vessels is associated with a number of disease conditions, including diabetic retinopathy and proliferative vit reo-retinopathy. In this study we describe a model of human retinal angioge nesis and show how this may be used to explain the mechanisms that are asso ciated with the growth of new retinal vessels. Methods. A 4 mm diameter disc of retinal tissue was placed within a fibrin matrix and the appearance was monitored daily by light microscopy. Immunohi stochemical techniques were used for the detection of, glial fibrillary aci dic protein, CD68, the Ki-67 antigen, vascular endothelial growth factor, m onocarboxylate transporter type 1 and von Willebrand's factor. Results. Vessels were evident extending from the periphery of the explant a nd the activation of endothelial cells was shown by immuno-peroxidase stain ing of paraffin embedded sections of the explants for the expression of the Ki-67 antigen, a marker of cell proliferation. The expression of glial fib rillary acidic protein and von Willebrand's factor increased with duration in culture and the presence of activated macrophages or microglia or both w as shown by positive immunoreactivity for CD68 and Ki-67 and were identifie d by day 3. The presence of endogenous vascular endothelial growth factor a nd the activation of monocarboxylate transporter type 1 by vascular endothe lial growth factor, showed the involvement of specific growth factors. Conclusion/interpretation. The explant model provides evidence for the invo lvement of macrophages and glial fibrillary acidic protein activation in hu man retinal angiogenesis and for the expression of monocarboxylate transpor ter type 1, which is likely to be important in the use of lactate in the hy poxic retina.