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Kathleen Jee, Murilo Wendeborn Rodrigues, Brooks Puchner, Junaid Hassan, Gerard A Lutty, Gregg Semenza, Silvia Montaner, Akrit Sodhi; Expression Pattern of HIF-1α and HIF-1-Regulated Angiogenic Mediators Suggests Utility of Circumferential Scatter Laser for Proliferative Sickle Retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5860.
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© ARVO (1962-2015); The Authors (2016-present)
Scatter laser photocoagulation is the standard of care for proliferative sickle retinopathy (PSR). Nonetheless, the efficacy of scatter laser for PSR – and the optimal location for laser application – is unclear. Therapies targeting vascular endothelial growth factor (VEGF) have therefore been proposed as an alternative treatment option for patients with PSR. However, whether anti-VEGF monotherapy is sufficient for the treatment of PSR is not known. To help address these questions, we examined the expression of hypoxia inducible factor (HIF)-1α, VEGF, and a second HIF-1-regulated angiogenic factor, angiopoietin-like 4 (ANGPTL4), recently implicated in the development of proliferative diabetic retinopathy (PDR), in PSR eyes.
Expression and localization of HIF-1α, VEGF, and ANGPTL4 were examined by immunohistochemistry in PSR eyes. Institutional Review Board approval was obtained from the Johns Hopkins University School of Medicine to collect aqueous and vitreous from patients with and without PSR and PDR. Aqueous and vitreous ANGPTL4 and VEGF levels were measured by enzyme-linked immunosorbent assay. Statistical analysis was performed using Mann-Whitney, Kruskal-Wallis, and Dunn’s multiple comparison tests.
HIF-1α, ANGPTL4, and VEGF expression were increased in Müller cells proximal and distal to the marginal zone between perfused and non-perfused retina in PSR patients (n=5). In the aqueous, ANGPTL4 levels were elevated in PSR (n=6; p=0.01) and PDR (n=5; p<0.001) patients relative to control patients (n=10), while VEGF levels were increased in PDR patients (p<0.01). In the vitreous, both ANGPTL4 and VEGF levels were elevated in PSR (n=1) and PDR (n=5; p<0.01) patients compared to control patients (n=5).
Our results suggest that anti-VEGF monotherapy may not be effective in PSR due to the expression of additional angiogenic factors, including ANGPTL4. The application of circumferential peripheral scatter laser anterior and posterior to the border of perfused and non-perfused retina may be beneficial to eliminate ischemic tissue and quench the expression of HIF-1-driven angiogenic mediators in PSR eyes.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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