PMID- 26823705
OWN - NLM
STAT- MEDLINE
DCOM- 20161031
LR  - 20181113
IS  - 1936-2625 (Electronic)
IS  - 1936-2625 (Linking)
VI  - 8
IP  - 11
DP  - 2015
TI  - Evidence of a novel gene HERPUD1 in polypoidal choroidal vasculopathy.
PG  - 13928-44
AB  - Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy, with 
      clinical features distinct from neovascular age-related macular degeneration 
      (nAMD) which is the leading cause of irreversible blindness in the elderly. Our 
      studies focused on the genetic background and function of a novel gene HERPUD1 in 
      PCV. HERPUD1 has been reported to increase the level of amyloid beta (Abeta), which is 
      a component of drusen deposits underlying the retinal pigment epithelium (RPE) 
      layer. To verify the genetic functional associations of HERPUD1 with PCV, exome 
      sequencing of HERPUD1 was performed in unrelated Chinese individuals, including 
      nAMD patients, PCV patients and control subjects. Immunohistochemistry assays for 
      HERPUD1 were performed in the subretinal membranes of PCV patients. The 
      relationship between HERPUD1 and amyloid beta precursor was determined using 
      real-time PCR in HERPUD1-overexpressing RPE cells. The gene expression patterns 
      of angiogenesis cytokines and chemokines in both Abeta-treated RPE cells and in 
      Brown Norway rats that received Abeta subretinal injections were determined. We 
      showed that HERPUD1 rs2217332 is significant associated with Chinese PCV, and 
      HERPUD1 was expressed in PCV subretinal membranes. Besides, Plasma Abeta42 protein 
      was significantly higher in PCV patients compared to nAMD and control subjects. 
      Abeta could upregulate angiogenic factors, chemokines and matrix metalloproteinases 
      both in RPE cells and in a rat model of subretinal Abeta injection. The imbalance of 
      the cytokines may be one of the mechanisms for the formation and development of 
      PCV. Our results strongly suggest that HERPUD1 is highly associated with PCV 
      patients.
FAU - Jin, Enzhong
AU  - Jin E
AD  - Department of Ophthalmology, Peking University People's Hospital; Key Laboratory 
      of Vision Loss and Restoration, Ministry of Education; Beijing Key Laboratory of 
      Diagnosis and Therapy of Retinal and Choroid Diseases Beijing 100044, P. R. 
      China.
FAU - Bai, Yujing
AU  - Bai Y
AD  - Department of Ophthalmology, Peking University People's Hospital; Key Laboratory 
      of Vision Loss and Restoration, Ministry of Education; Beijing Key Laboratory of 
      Diagnosis and Therapy of Retinal and Choroid Diseases Beijing 100044, P. R. 
      China.
FAU - Huang, Lvzhen
AU  - Huang L
AD  - Department of Ophthalmology, Peking University People's Hospital; Key Laboratory 
      of Vision Loss and Restoration, Ministry of Education; Beijing Key Laboratory of 
      Diagnosis and Therapy of Retinal and Choroid Diseases Beijing 100044, P. R. 
      China.
FAU - Zhao, Min
AU  - Zhao M
AD  - Department of Ophthalmology, Peking University People's Hospital; Key Laboratory 
      of Vision Loss and Restoration, Ministry of Education; Beijing Key Laboratory of 
      Diagnosis and Therapy of Retinal and Choroid Diseases Beijing 100044, P. R. 
      China.
FAU - Zhang, Chunfang
AU  - Zhang C
AD  - Clinical Epidemiology & Biostatistics, Peking University People's Hospital 
      Beijing 100044, P. R. China.
FAU - Zhao, Mingwei
AU  - Zhao M
AD  - Department of Ophthalmology, Peking University People's Hospital; Key Laboratory 
      of Vision Loss and Restoration, Ministry of Education; Beijing Key Laboratory of 
      Diagnosis and Therapy of Retinal and Choroid Diseases Beijing 100044, P. R. 
      China.
FAU - Li, Xiaoxin
AU  - Li X
AD  - Department of Ophthalmology, Peking University People's Hospital; Key Laboratory 
      of Vision Loss and Restoration, Ministry of Education; Beijing Key Laboratory of 
      Diagnosis and Therapy of Retinal and Choroid Diseases Beijing 100044, P. R. 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151101
PL  - United States
TA  - Int J Clin Exp Pathol
JT  - International journal of clinical and experimental pathology
JID - 101480565
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Angiogenic Proteins)
RN  - 0 (Chemokines)
RN  - 0 (HERPUD1 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/genetics/metabolism
MH  - Angiogenic Proteins/metabolism
MH  - Animals
MH  - Case-Control Studies
MH  - Cell Line
MH  - Chemokines/metabolism
MH  - Choroidal Neovascularization/diagnosis/*genetics/metabolism/pathology
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression Regulation
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinases/metabolism
MH  - Membrane Proteins/*genetics/metabolism
MH  - Middle Aged
MH  - Peptide Fragments/metabolism
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
MH  - Rats, Inbred BN
MH  - Retinal Pigment Epithelium/*metabolism/pathology
MH  - Risk Factors
MH  - Time Factors
MH  - Transfection
PMC - PMC4713491
OTO - NOTNLM
OT  - HERPUD1
OT  - amyloid beta
OT  - angiogenesis
OT  - polypoidal choroidal vasculopathy
OT  - single-nucleotide polymorphism (SNP)
EDAT- 2016/01/30 06:00
MHDA- 2016/11/01 06:00
PMCR- 2015/11/01
CRDT- 2016/01/30 06:00
PHST- 2015/09/22 00:00 [received]
PHST- 2015/10/25 00:00 [accepted]
PHST- 2016/01/30 06:00 [entrez]
PHST- 2016/01/30 06:00 [pubmed]
PHST- 2016/11/01 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
PST - epublish
SO  - Int J Clin Exp Pathol. 2015 Nov 1;8(11):13928-44. eCollection 2015.