Background/aims-Preretinal neovascular formations called sea fans develop at the border of non-perfused peripheral retina in sickle cell retinopathy. Angiogenic factors which could contribute to their development, however, have not been examined previously. The objective of this study was to determine immunohistochemically if vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) were associated with sea fan formations. Methods-Immunohistochemistry on cryosections was used to localise bFGF, VEGF, heparan sulphate proteoglycan, human serum albumin, collagens IV and II, and von Willebrand factor in tissue from five sickle cell and one control subject. Results-The greatest immunoreactivity for VEGF and bFGF was in the feeder and preretinal vessels of sea fans (p<0.01). The most prominent reaction product was localised to vascular endothelial cells. In retinal vessels, VEGF and bFGF immunoreactivities were greater in sickle cell subjects (both proliferative and nonproliferative) than in the control subject (p<0.01 and p<0.02 respectively). In the sickle cell retina, no angiogenic factor immunoreactivity was detected in nonperfused periphery and there was no significant diVerence in bFGF or VEGF immunoreactivity between perfused retina and the border of perfused and non-perfused areas. Conclusion-Our results demonstrate for the first time that VEGF and bFGF are associated with sea fan formations in sickle cell retinopathy. Both factors may function in an autocrine manner because immunoreactivity for these factors was greater within the neovascularisation than in adjacent retina. (Br J Ophthalmol 1999;83:838-846)

This in vitro analysis suggests that adenosine may stimulate retinal vasculogenesis, an event which involves migration of angioblasts and their assembly into vascular cords, prior to canalization.

Aims: The expression of the adhesion molecules ICAM-1, VCAM-1, and P-selectin, and the distribution and number of polymorphonuclear leucocytes (PMNs) were investigated in sickle cell retinopathy (SCR) and compared to the normal retina. Methods: Postmortem ocular tissue was obtained from five subjects (16,21,28,40, and 41 years of age) with sickle haemoglobinopathies and from one control subject. Tissue was cryopreserved, and streptavidin peroxidase immunohistochemistry was performed with antibodies against ICAM-1, VCAM-1, and P-selectin. Immunohistochemical reaction product was scored, and PMN numbers were counted in sections stained with non-specific esterase. Results: Increased ICAM-1, VCAM-1, and P-selectin immunoreactivities were observed in sickle cell subjects compared to the control subject. The highest ICAM and P-selectin immunoreactivity was associated with intraretinal vessels adjacent to the preretinal neovascular formation in subjects with proliferative retinopathy. This was not the case with VCAM-1 immunoreactivity, which was highest in intraretinal vessels adjacent to the sea fan when the sea fan was still "in statu nascendi." Fully formed, "older" sea fans had the highest levels of VCAM-1. The increase in adhesion molecule immunoreactivity was paralleled by an increase in intraretinal PMNs. The number of intraretinal PMNs increased with progression of the disease and the numbers surpassed those in control subjects by threefold. In the sea fan with the greatest VCAM-1 immunoreactivity, there were 20 times more PMNs were observed than in the rest of the retina in the same subject. Conclusion: These data suggest that adhesion molecule mediated leucocyte adhesion might play an important part in the vaso-occlusive phase of sickle cell retinopathy and in autoinfarction of sea fan formations.