Increased circulating PEDF and low sICAM-1 are associated with sickle cell retinopathy

Cruz, Pedro Rodrigues Sousa da; Lira, Rodrigo Pessoa Cavalcanti; Filho, Silva; Souza, Bruno Batista de; Mitsuushi, Fabio N.; Menaa, Farid; Fertrin, Kleber Yotsumoto; Vasconcellos, José Paulo Cabral de; Conran, Nicola; Costa, Fernando Ferreira; Melo, Mônica Barbosa de

doi:10.1016/j.bcmd.2014.08.003

Cited by 17 publications

(27 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High levels of stromal-derived factor-1, augmented PlGF and discretely elevated PDGF-BB have been associated with pulmonary hypertension or high tricuspid regurgitation velocity in SCD, 13,16,19 while increased pigment epithelium-derived factor has been related to SCD retinopathy. 15 Here we present data demonstrating that the profile of circulating angiogenic factors is significantly altered in SCD individuals, with corresponding effects on plasma angiogenic activity.…”

Section: Discussionmentioning

confidence: 77%

“…While evidence supports the existence of an elevated production of pro-angiogenic factors in SCD, [12][13][14][15]31,32 few studies are available to establish a clear link between angiogenic factor production and pathological neovascularization in this disease. High levels of stromal-derived factor-1, augmented PlGF and discretely elevated PDGF-BB have been associated with pulmonary hypertension or high tricuspid regurgitation velocity in SCD, 13,16,19 while increased pigment epithelium-derived factor has been related to SCD retinopathy.…”

Section: Discussionmentioning

confidence: 99%

“…11 The levels of a number of angiogenic mediators have been reported to be elevated in SCD, including vascular endothelial growth factor (VEGF), placental growth factor (PlGF), angiopoietin-1 (Ang1), angiopoietin-2 (Ang2) and erythropoietin (EPO). [12][13][14][15][16] In addition, despite the heterogeneity of the SCD phenotype, several clinical manifestations associated with SCD, including proliferative retinopathy, pulmonary hypertension, leg ulcers and moyamoya syndrome, suggest an involvement of pathological angiogenic processes. [17][18][19][20][21][22][23][24] Although these observations indicate an angiogenic imbalance in SCD, the existence of pro-angiogenic mechanisms in SCD, and their consequences, remain unclear.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Key endothelial cell angiogenic mechanisms are stimulated by the circulating milieu in sickle cell disease and attenuated by hydroxyurea

et al. 2015

Self Cite

View full text Add to dashboard Cite

ABSTRACTas a therapy in SCD. 25 Hydroxyurea is a cytostatic drug that inhibits ribonucleotide reductase, arresting cell division in the S-phase; additionally, data suggest that hydroxyurea can generate nitric oxide following administration. 26 We recently reported that hydroxyurea exerts anti-angiogenic effects in VEGF-dependent EC angiogenic in vitro assays and inhibits VEGF-dependent neovascularization in Matrigel implants in C57BL/6 mice. 27 This anti-angiogenic activity appears to be mediated by the down-regulation of endothelial hypoxia-inducible factor-1α (HIF-1α) expression, and consequent modulation of miRNA 221 expression, leading to the inhibition of EC proliferation and invasion/migration. 27To lend further support to the hypothesis of an unbalanced angiogenic state in SCD, we investigated the in vitro effects of plasma from patients with SCD on key steps of EC angiogenic behavior, namely, proliferative capability, invasive capacity and the formation of capillary-like EC structures. The plasma contents of angiogenic factors were associated with these data, as was the incidence of proliferative retinopathy in HbSC patients, a clinical manifestation thought to reflect augmented angiogenesis. 28The angiogenic activity of plasma from patients on hydroxyurea therapy was also examined. Finally, to confirm that SCD pathophysiology is associated with exacerbated angiogenesis, in vivo neovascularization was examined in a SCD mouse model, compared with non-SCD mice, utilizing a Matrigel plug angiogenesis assay. Methods PatientsPatients with HbSS or HbSC disease (collectively termed SCD) were recruited, during steady-state, at the Hematology Center, UNICAMP (Table 1). Details on the diagnosis of HbSS/HbSC, our definition of steady-state and criteria for commencing hydroxyurea therapy (15-30 mg hydroxyurea/kg/day) are given in the Online Supplementary Information. All patients had undergone ophthalmoscopy and fluorescein angiography for detection of proliferative retinopathy. A total of 29 HbSS patients, who did not have proliferative retinopathy, were recruited into the study. A total of 33 HbSC patients were recruited, of whom 16 did not have proliferative retinopathy (SC group) and 17 did (SCR group). One HbSC patient had been prescribed hydroxyurea following an ischemic stroke. Homozygous hemoglobin A (HbAA) healthy controls were age-and gender-matched, where possible. Informed written consent was obtained from all participants and the study was approved by the UNICAMP Ethics Committee, in accordance with national guidelines. Bioplex assayThe Fluorokine ® MAP, Human Angiogenesis Custom Premix Kit A (R&D Systems, Minneapolis, USA) was used to quantify Ang1, basic fibroblast growth factor (bFGF), PlGF, platelet-derived growth factor (PDGF)-AA, PDGF-BB, VEGF, VEGF-D, endostatin and thrombospondin-2 (TSP-2) in plasma, according to the manufacturer's instructions. The preparation of the plasma for the assay is described in the Online Supplementary Information. In vitro culture of human umbilical vein endothelial c...

show abstract

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Key endothelial cell angiogenic mechanisms are stimulated by the circulating milieu in sickle cell disease and attenuated by hydroxyurea

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…[33] Elevation of PEDF production appears to follow increased angiogenesis. [34] In addition, plasma angiopoietins (Ang-1 and Ang-2) and von Willebrand factor are present in higher levels in SCD patients compared to controls. [35]…”

Section: Resultsmentioning

confidence: 99%

New Ways to Detect Pediatric Sickle Cell Retinopathy: A Comprehensive Review

Pahl

Green²,

Bhatia³

et al. 2017

Journal of Pediatric Hematology/Oncology

View full text Add to dashboard Cite

Sickle retinopathy reflects disease-related vascular injury of the eye, which can potentially result in visual loss from vitreous hemorrhage or retinal detachment. Here we review sickle retinopathy among children with sickle cell disease, describe the epidemiology, pediatric risk factors, pathophysiology, ocular findings and treatment. Newer, more sensitive ophthalmological imaging modalities are available for retinal imaging, including ultra-widefield fluorescein angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography. Optical coherence tomography angiography provides a non-invasive view of retinal vascular layers that could previously not be imaged and can be quantified for comparative or prospective analyses. Ultra-widefield fluorescein angiography provides a more comprehensive view of the peripheral retina than traditional imaging techniques. Screening for retinopathy by standard fundoscopic imaging modalities detects a prevalence of approximately 10%. In contrast, these more sensitive methods allow for more sensitive examination that includes the retina perimeter where sickle retinopathy is often first detectable. Use of these new imaging modalities may detect a higher prevalence of early sickle pathology among children than has previously been reported. Earlier detection may help in better understanding the pathogenesis of sickle retinopathy and guide future screening and treatment paradigms.

show abstract

“…Knowledge regarding the origin and retinal distribution of proangiogenic factors may be relevant for proper targeting and delivery of retinal laser treatment. Pigment epithelium derived factor (PEDF) was elevated in HbSC patients with PSR [47]. Increased ICAM-1, VCAM-1, and P-selectin immunoreactivities have also been observed in PSR subjects [48].…”

Section: Advances In Sickle Cell Retinopathy Ocular Biologymentioning

confidence: 99%

Sickle cell retinopathy. A focused review

Elsayed

Mura

Dhibi

et al. 2019

Graefes Arch Clin Exp Ophthalmol

View full text Add to dashboard Cite

Purpose To provide a focused review of sickle cell retinopathy in the light of recent advances in the pathogenesis, multimodal retinal imaging, management of the condition, and migration trends, which may lead to increased prevalence of the condition in the Western world. Methods Non-systematic focused literature review. Results Sickle retinopathy results from aggregation of abnormal hemoglobin in the red blood cells in the retinal microcirculation, leading to reduced deformability of the red blood cells, stagnant blood flow in the retinal precapillary arterioles, thrombosis, and ischemia. This may be precipitated by hypoxia, acidosis, and hyperosmolarity. Sickle retinopathy may result in sight threatening complications, such as paracentral middle maculopathy or sequelae of proliferative retinopathy, such as vitreous hemorrhage and retinal detachment. New imaging modalities, such as wide-field imaging and optical coherence tomography angiography, have revealed the microstructural features of sickle retinopathy, enabling earlier diagnosis. The vascular growth factor ANGPTL-4 has recently been identified as a potential mediator of progression to proliferative retinopathy and may represent a possible therapeutic target. Laser therapy should be considered for proliferative retinopathy in order to prevent visual loss; however, the evidence is not very strong. With recent development of wide-field imaging, targeted laser to ischemic retina may prove to be beneficial. Exact control of intraoperative intraocular pressure, including valved trocar vitrectomy systems, may improve the outcomes of vitreoretinal surgery for complications, such as vitreous hemorrhage and retinal detachment. Stem cell transplantation and gene therapy are potentially curative treatments, which may prevent retinopathy. Conclusions There is lack of evidence regarding the optimal management of sickle retinopathy. Further study is needed to determine if recent progress in the understanding of the pathophysiology and diagnosis of sickle retinopathy may translate into improved management and outcome.

show abstract

Increased circulating PEDF and low sICAM-1 are associated with sickle cell retinopathy

Cited by 17 publications

References 30 publications

Key endothelial cell angiogenic mechanisms are stimulated by the circulating milieu in sickle cell disease and attenuated by hydroxyurea

Key endothelial cell angiogenic mechanisms are stimulated by the circulating milieu in sickle cell disease and attenuated by hydroxyurea

New Ways to Detect Pediatric Sickle Cell Retinopathy: A Comprehensive Review

Sickle cell retinopathy. A focused review

Contact Info

Product

Resources

About