Histopathologic Features of Neovascularization in Sickle Cell Retinopathy

British Journal of Ophthalmology

et al. 1999

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)

Section: Resultsmentioning

confidence: 99%

Angiogenic factors in human proliferative sickle cell retinopathy

Cao

Mathews

British Journal of Ophthalmology

et al. 1999

“…It is important to note that the staining pattern seen in whole-mount preparations was identical using both ADPase enzyme histochemistry (Lutty and McLeod, 1992;Chan-Ling et al, 2004) and CD39 immunohistochemistry in the fetal human as a marker for angioblasts and blood vessels. It is present in adult retinal endothelial cells of all species studied to date and we have used it to study pathological neovascularization in sickle cell and diabetic retinopathy as well as retinopathy of prematurity McLeod, 1992, 2005;McLeod et al, 1993McLeod et al, , 1996bMcLeod et al, , 1997Lutty et al, 1994Lutty et al, , 1996. CD39, or nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), is the major vascular endothelial ecto-nucleotidase and hydrolyses nucleoside triphosphates and diphosphates, ultimately to the nucleoside analogues (Goepfert et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

The initial fetal human retinal vasculature develops by vasculogenesis

Hasegawa

Prow

et al. 2006

Developmental Dynamics

Self Cite

There is increasing evidence that the hemangioblast, a common progenitor for hematopoietic cells and endothelial cells, participates in embryonic and extra-embryonic vasculogenesis in some organs. Whether resident angioblasts or endothelial progenitor cells (EPCs) contribute to human retinal vasculogenesis is still a matter of controversy. To address this controversy, fetal human retinas of 6 -23 weeks gestation (WG) were examined using immunohistochemistry and a panel of antibodies against endothelial cell markers (CD34, CD31), a marker for retinal angioblasts and endothelium (CD39/ecto-ADPase), and a marker for precursors and hemangioblasts (CXCR4). Confocal microscopic spectral analysis and double labeling with Ki67 was used to identify the proliferating cell types. In the inner neuroblastic layer of the 6 -8 WG retina and in the putative ganglion cell layer in avascular regions of older eyes (14 WG-20 WG), scattered CD39 ؉ angioblasts were well in advance of forming vasculature. There was a layer of CXCR4 ؉ cells in the inner retina that was reduced in size with development. As blood vessels formed, CD39؉ cells were always well in advance of the vascular front and they expressed CXCR4. This demonstrates that a pool of resident angioblasts express CD39 and CXCR4 as they differentiate and participate in vasculogenesis in the fetal human. They retain expression of CD39 as endothelial cells in the newly formed retinal vasculature but they down-regulate CXCR4 expression. Developmental Dynamics 235:3336 -3347, 2006.

“…2 The peripheral occlusions in children are primarily in capillaries but, with age, the occlusions occur in major blood vessels as well, and the peripheral retina becomes avascular. [2][3][4] At the sites of occlusion, hairpin loops and arteriovenous anastomoses may form, resulting in abnormal blood flow. Preretinal neovascularisation, called sea fans, also forms adjacent to non-perfused peripheral retina.…”

mentioning

confidence: 99%

Neutrophils and leucocyte adhesion molecules in sickle cell retinopathy

Mathews

British Journal of Ophthalmology

Merges

et al. 2002

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.