title: TMP prevents retinal neovascularization and imparts neuroprotection in an oxygen-induced retinopathy model.
abstract: OBJECTIVE
  To evaluate the effects of tetramethylpyrazine (TMP) on retinal neovascularization (NV) and neuroprotection in an oxygen-induced retinopathy (OIR) model.
  
  
  METHODS
  Neonatal C57BL/6J mice were subjected to 75% oxygen from postnatal day 7 (P7) to P12 and then returned to room air. TMP (200 mg/kg) or normal saline was given daily from P12 to P17. Immunostaining, HE staining, TUNEL assay, and RT-PCR were used to assess the effects of TMP on retinal neurovascular repair.
  
  
  RESULTS
  TMP effectively prevented pathologic NV and accelerated physiologic revascularization by enhancing the formation of endothelial tip cells at the edges of the repairing capillary networks and preserving the astrocytic template in the avascular retina. TMP also prevented morphologic changes and significantly decreased TUNEL-positive cells in the avascular retina by rescuing neurons such as amacrine, rod bipolar, horizontal, and Müller cells. In TMP-treated mice retinas, there was a less obvious loss of amacrine cell bodies and their distinct bands; the number of both rod bipolar and horizontal cell bodies, as well as the density of their dendrites in the outer plexiform layer, was greater than that in OIR control mice. TMP not only decreased the loss of alignment of Müller cell bodies and distortion of processes but reduced the reactive expression of GFAP in Müller cells. Furthermore, HIF-1α and VEGF mRNA expression were downregulated in TMP-treated mice retinas.
  
  
  CONCLUSIONS
  TMP improved neurovascular recovery by preventing NV and protecting retinal astroglia cells and neurons from ischemia-induced cell death partially due to its downregulation of HIF-1α and VEGF mRNA expression.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. liangxlsums@yahoo.com.cn
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liang
authors.forename: Huanjiao
authors.initials: H
authors.lastname: Zhou
authors.forename: Yungang
authors.initials: Y
authors.lastname: Ding
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Shiqing
authors.initials: S
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Sun
authors.forename: Xulong
authors.initials: X
authors.lastname: Liao
authors.forename: Wang
authors.initials: W
authors.lastname: Min
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D020287:In Situ Nick-End Labeling; D030004:Ligusticum / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010100:Oxygen / Q000633:toxicity; D011719:Pyrazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D015861:Retinal Neovascularization / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D055351:Retinal Neurons / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004365:Drugs, Chinese Herbal; D005904:Glial Fibrillary Acidic Protein; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011719:Pyrazines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; C528900:glial fibrillary astrocytic protein, mouse; C467480:vascular endothelial growth factor A, mouse; D010100:Oxygen; C017953:tetramethylpyrazine