PMID- 30917905
OWN - NLM
STAT- MEDLINE
DCOM- 20200217
LR  - 20200217
IS  - 1096-0007 (Electronic)
IS  - 0014-4835 (Linking)
VI  - 182
DP  - 2019 May
TI  - Intravenous injection of l-aspartic acid beta-hydroxamate attenuates choroidal 
      neovascularization via anti-VEGF and anti-inflammation.
PG  - 93-100
LID - S0014-4835(19)30012-0 [pii]
LID - 10.1016/j.exer.2019.03.018 [doi]
AB  - Choroidal neovascularization (CNV) is a hallmark of exudative age-related macular 
      degeneration (exAMD) and a major cause of visual loss in AMD. Despite the 
      widespread use of anti-VEGF therapy, serious adverse effects arise from repeated 
      intravitreal injection of anti-VEGF antibodies, which warrant alternative 
      strategy. We report herein that in a CNV murine model created by krypton red 
      laser, intravenous injection of a serine racemase inhibitor, l-Aspartic acid 
      beta-hydroxamate (L-ABH), significantly reduced CNV at the dose 6 mg/kg on the first 
      day before and followed by 3 mg/kg on the third day after laser injury. The CNV 
      volumes were analyzed with isolectin GS-IB4 staining on choroidal/RPE flat mounts 
      on the seventh day after laser injury. Injection of L-ABH did not produce 
      negative effects on retinal function and visual behavior. To dissect the 
      mechanism in vitro, pretreatment with L-ABH in primary RPE cultures significantly 
      reduced production of vascular endothelial growth factor (VEGF) and macrophage 
      chemotactic protein 1 (MCP-1) by TNFalpha-primed RPEs. Consistent with these 
      observations, L-ABH pretreatment significantly attenuated macrophage migration 
      mediated by TNFalpha-primed RPE. Collectively, intravenous injection of L-ABH 
      significantly reduced CNV volumes via reducing production of VEGF and MCP-1 by 
      inflammation-primed RPEs.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Wu, Mengjuan
AU  - Wu M
AD  - School of Optometry and Ophthalmology and the Eye Hospital, Wenzhou Medical 
      University, China; State Key Laboratory of Optometry, Ophthalmology, and Visual 
      Science, Wenzhou, Zhejiang, 325027, China.
FAU - Liu, Yimei
AU  - Liu Y
AD  - School of Optometry and Ophthalmology and the Eye Hospital, Wenzhou Medical 
      University, China; State Key Laboratory of Optometry, Ophthalmology, and Visual 
      Science, Wenzhou, Zhejiang, 325027, China.
FAU - Zhang, He
AU  - Zhang H
AD  - School of Optometry and Ophthalmology and the Eye Hospital, Wenzhou Medical 
      University, China; State Key Laboratory of Optometry, Ophthalmology, and Visual 
      Science, Wenzhou, Zhejiang, 325027, China.
FAU - Lian, Meiling
AU  - Lian M
AD  - School of Optometry and Ophthalmology and the Eye Hospital, Wenzhou Medical 
      University, China; State Key Laboratory of Optometry, Ophthalmology, and Visual 
      Science, Wenzhou, Zhejiang, 325027, China.
FAU - Chen, Juan
AU  - Chen J
AD  - School of Optometry and Ophthalmology and the Eye Hospital, Wenzhou Medical 
      University, China; State Key Laboratory of Optometry, Ophthalmology, and Visual 
      Science, Wenzhou, Zhejiang, 325027, China.
FAU - Jiang, Haiyan
AU  - Jiang H
AD  - School of Optometry and Ophthalmology and the Eye Hospital, Wenzhou Medical 
      University, China; State Key Laboratory of Optometry, Ophthalmology, and Visual 
      Science, Wenzhou, Zhejiang, 325027, China.
FAU - Xu, Ying
AU  - Xu Y
AD  - Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, 
      Guangzhou, Guangdong, 510632, China.
FAU - Shan, Ge
AU  - Shan G
AD  - CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for 
      Excellence in Molecular Cell Science, School of Life Sciences, University of 
      Science and Technology of China, Hefei, Anhui, 230027, China.
FAU - Wu, Shengzhou
AU  - Wu S
AD  - School of Optometry and Ophthalmology and the Eye Hospital, Wenzhou Medical 
      University, China; State Key Laboratory of Optometry, Ophthalmology, and Visual 
      Science, Wenzhou, Zhejiang, 325027, China. Electronic address: wszlab@wmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190324
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 20154-32-9 (beta-aspartylhydroxamic acid)
RN  - 7006-34-0 (Asparagine)
SB  - IM
MH  - Angiogenesis Inhibitors/*administration & dosage
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage
MH  - Asparagine/administration & dosage/*analogs & derivatives
MH  - Cells, Cultured
MH  - Choroid/pathology
MH  - Choroidal Neovascularization/*drug therapy/metabolism/pathology
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Inflammation/*drug therapy/metabolism/pathology
MH  - Injections, Intravenous
MH  - Intravitreal Injections
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Retinal Pigment Epithelium/metabolism/pathology
MH  - Vascular Endothelial Growth Factor A/antagonists & inhibitors
MH  - Visual Acuity
OTO - NOTNLM
OT  - Age-related macular degeneration
OT  - Macrophage chemotactic protein 1
OT  - Phenazine methosulfate
OT  - Retinal pigment epithelial cell
OT  - Transwell migration
OT  - VEGF
OT  - l-Aspartic acid beta-hydroxamate
EDAT- 2019/03/29 06:00
MHDA- 2020/02/18 06:00
CRDT- 2019/03/29 06:00
PHST- 2019/01/03 00:00 [received]
PHST- 2019/02/26 00:00 [revised]
PHST- 2019/03/19 00:00 [accepted]
PHST- 2019/03/29 06:00 [pubmed]
PHST- 2020/02/18 06:00 [medline]
PHST- 2019/03/29 06:00 [entrez]
AID - S0014-4835(19)30012-0 [pii]
AID - 10.1016/j.exer.2019.03.018 [doi]
PST - ppublish
SO  - Exp Eye Res. 2019 May;182:93-100. doi: 10.1016/j.exer.2019.03.018. Epub 2019 Mar 
      24.