title: Expression Pattern of HIF-1α and VEGF Supports Circumferential Application of Scatter Laser for Proliferative Sickle Retinopathy.
abstract: Retinal vascular occlusions in sickle cell anemia patients cause tissue ischemia and the release of angiogenic mediators that promote the development of retinal neovascularization, initiating proliferative sickle retinopathy (PSR). Laser photocoagulation (LPC) has emerged as the most common treatment for PSR. Nonetheless, only two randomized controlled clinical trials have evaluated the use of LPC for PSR, and both failed to definitively demonstrate efficacy of this approach. This may be due to a lack of knowledge regarding the appropriate location for placement of laser coagulations in PSR eyes. To help address this question, we examined the expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) in PSR eyes.
  
  
  
  The expression pattern of HIF-1α and VEGF in PSR (n = 5) and control (n = 3) eyes was examined by immunohistochemistry in different retinal regions defined by the presence or absence of retinal vessels.
  
  
  
  Hypoxia-inducible factor 1α and VEGF were expressed in the inner retina of 5/5 untreated PSR eyes adjacent to retinal neovascularization; expression of HIF-1α was not detected (and VEGF only lightly detected) in normal retinal and choroidal vasculature of 3/3 control eyes. Hypoxia-inducible factor 1α and VEGF were strongly expressed in retinal cells within avascular (nonperfused) retina, anterior to the boundary between perfused and nonperfused retina, as well as in posterior ischemic retina in the presence or absence of neovascular sea fans.
  
  
  
  If the goal of LPC in PSR is to quench the expression of HIF-1-driven angiogenic mediators, our results support broad application of peripheral laser for its treatment.
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Murilo
authors.initials: M
authors.lastname: Rodrigues
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Kashiwabuchi
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Monika
authors.initials: M
authors.lastname: Deshpande
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Jee
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Morton F
authors.initials: MF
authors.lastname: Goldberg
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Gerard
authors.initials: G
authors.lastname: Lutty
authors.affiliation: Departments of Pediatrics, Medicine, Oncology, Radiation Oncology, Biological Chemistry, and Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Gregg L
authors.initials: GL
authors.lastname: Semenza
authors.affiliation: Department of Oncology and Diagnostic Sciences, School of Dentistry; Department of Pathology, School of Medicine; Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland, United States.
authors.forename: Silvia
authors.initials: S
authors.lastname: Montaner
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
authors.forename: Akrit
authors.initials: A
authors.lastname: Sodhi
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications* / Q000175:diagnosis; D002102:Cadaver; D002829:Choroid / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D017075:Laser Coagulation; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015861:Retinal Neovascularization / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D012171:Retinal Vessels / Q000000981:diagnostic imaging / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D018630:Vitreoretinopathy, Proliferative / Q000209:etiology / Q000378:metabolism* / Q000601:surgery
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A