Abstract
Purpose: :
Hemoglobinopathies are among the most common inherited diseases globally. The HbS and HbC variants of the Beta globin gene (HBB) lead to sickle cell anemia (SS) and SC hemoglobinopathies. Sickled red blood cells are more likely to adhere to the vascular endothelium, resulting in vascular obstruction and hypoxia. Sickle cell retinopathy (SCR) is an ocular condition derived from vaso-occlusion in the microvasculature of the retina resulting in hypoxia and neovascularization, which can lead to partial or total vision loss. In addition to vascular obstruction by abnormal red blood cells, other factors such as endothelial and leukocyte activation, as well as angiogenic factors and their antagonists expression contribute to the pathophysiology. The purpose of this study was to evaluate the involvement of the plasmatic proteins sICAM-1, sVCAM-1, P-selectin, Ang-1, Ang-2 and VEGF with the pathophysiology of SCR.
Methods: :
Proteins were quantified through enzyme-linked immunosorbent assay (ELISA) in the plasma of 18 patients affected by sickle cell retinopathy (10 SC and 8 SS) and 18 (7 SC and 11 SS) sickle cell disease subjects presenting normal high resolution ocular fundus photography examination, along with eight healthy sex and age-matched subjects.
Results: :
Comparing group medians by Mann-Whitney test, a tendency of higher plasma concentration of VEGF (p-value = 0.3825), P-selectin (p-value = 0.4941) and Ang-1 (p-value = 0.3135) was observed in the retinopathy-affected group in relation to non-retinopathy group. In contrast, sICAM-1 (p-value = 0.6504) and sVCAM-1 (p-value = 0.1419) reached higher mean values in the non-retinopathy group in respect to its counterpart, albeit all failed to reach statistical significance. On the other hand, Ang-2 mean plasma concentration was significantly higher in the non-affected group in relation to the retinopathy-affected group (p-value = 0.0476) and controls (p-value = 0.0022).
Conclusions: :
These findings must be complemented with more samples to test the observed tendencies. Nonetheless, data shown here are consistent with evidences that Ang-2 may play a role as a context-dependent antagonist of Ang-1, through functioning as a competitive ligand to the tyrosine kinase Tie-2 receptor in endothelial cells. The inhibition of the Ang-1/Tie-2 by Ang-2 may interfere in the essential Ang-1 induced processes of cell survival and migration during angiogenesis.
Keywords: retinal neovascularization • retina • protective mechanisms