title: Neonatal hyperglycemia inhibits angiogenesis and induces inflammation and neuronal degeneration in the retina.
abstract: Recent evidence suggests that transient hyperglycemia in extremely low birth weight infants is strongly associated with the occurrence of retinopathy of prematurity (ROP). We propose a new model of Neonatal Hyperglycemia-induced Retinopathy (NHIR) that mimics many aspects of retinopathy of prematurity. Hyperglycemia was induced in newborn rat pups by injection of streptozocine (STZ) at post natal day one (P1). At various time points, animals were assessed for vascular abnormalities, neuronal cell death and accumulation and activation of microglial cells. We here report that streptozotocin induced a rapid and sustained increase of glycemia from P2/3 to P6 without affecting rat pups gain weight or necessitating insulin treatment. Retinal vascular area was significantly reduced in P6 hyperglycemic animals compared to control animals. Hyperglycemia was associated with (i) CCL2 chemokine induction at P6, (ii) a significant recruitment of inflammatory macrophages and an increase in total number of Iba+ macrophages/microglia cells in the inner nuclear layer (INL), and (iii) excessive apoptosis in the INL. NHIR thereby reproduces several aspects of ischemic retinopathies, including ROP and diabetic retinopathies, and might be a useful model to decipher hyperglycemia-induced cellular and molecular mechanisms in the small rodent.
authors.affiliation: INSERM UMRS872, Centre de Recherche des Cordeliers, Paris, France ; Paris Descartes University, Paris, France ; AP-HP, Necker-Enfants malades Hospital, Paris, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Kermorvant-Duchemin
authors.forename: Alexis Christophe
authors.initials: AC
authors.lastname: Pinel
authors.forename: Sophie
authors.initials: S
authors.lastname: Lavalette
authors.forename: Delphine
authors.initials: D
authors.lastname: Lenne
authors.forename: William
authors.initials: W
authors.lastname: Raoul
authors.forename: Bertrand
authors.initials: B
authors.lastname: Calippe
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.forename: Xavier
authors.initials: X
authors.lastname: Guillonneau
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology; D051381:Rats; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000209:etiology* / Q000378:metabolism*; D013311:Streptozocin / Q000633:toxicity
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D013311:Streptozocin