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Neutrophils and leucocyte adhesion molecules in sickle cell retinopathy

Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Correspondence to:
Correspondence to:
Gerard A Lutty, PhD, 170 Woods Research Building, Wilmer Ophthalmological Institute, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD, 21287-9115, USA;
glutty{at}jhmi.edu

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.

Keywords: ICAM-1; neutrophils; P-selectin; sickle cell; vaso-occlusions; VCAM-1

Abbreviations: ICAM-1, intercellular adhesion molecule 1; IL-1, interleukin ; NSE, non-specific esterase; PMN, polymorphonuclear leucocytes; SCR, sickle cell retinopathy; sRBCs, sickle erythrocytes; TNF, tumour necrosis factor ; VCAM-1, vascular adhesion molecule 1; WBC, white blood cells; vWf, von Willebrand factor

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