PMID- 19823802
OWN - NLM
STAT- MEDLINE
DCOM- 20100423
LR  - 20220309
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 52
IP  - 12
DP  - 2009 Dec
TI  - Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early 
      stages of diabetic retinopathy.
PG  - 2633-41
LID - 10.1007/s00125-009-1548-8 [doi]
AB  - AIMS/HYPOTHESIS: Interphotoreceptor retinoid-binding protein (IRBP) plays a major 
      role in the visual cycle and is essential to the maintenance of photoreceptors. 
      The aim of this study was to determine whether a decrease in IRBP production 
      exists in the early stages of diabetic retinopathy. METHODS: Vitreous samples 
      from diabetic patients with proliferative and non-proliferative diabetic 
      retinopathy (PDR, NPDR), and from non-diabetic patients with macular hole 
      (control group) were selected for IRBP quantitative assessment by proteomic 
      analysis (fluorescence-based difference gel electrophoresis) and western blot. 
      Human post mortem eyes (n = 16) from diabetic donors without clinically 
      detectable retinopathy and from non-diabetic donors (n = 16) were used to 
      determine IRBP (also known as RBP3) mRNA levels (RT-PCR) and protein content 
      (western blot and confocal microscopy). Retinal neurodegeneration was assessed by 
      measuring glial fibrillar acidic protein (GFAP) and the apoptotic rate. Y79 human 
      retinoblastoma cells were used to test the effects of glucose, TNF-alpha and 
      IL-1beta on IRBP expression and IRBP levels. RESULTS: Intravitreous IRBP 
      concentration was significantly lower in PDR < NPDR < control in proteomic and 
      western blot analysis. IRBP mRNA levels and IRBP protein content were 
      significantly lower in the retinas from diabetic donors than in those from 
      non-diabetic donors. Increased GFAP and a higher degree of apoptosis were 
      observed in diabetic retinas compared with non-diabetic retinas. A dose-dependent 
      downregulation of IRBP mRNA expression and IRBP content was detected with 
      glucose, TNF-alpha and IL-1beta in cultures of Y79 human retinoblastoma cells. 
      CONCLUSIONS/INTERPRETATION: Underproduction of IRBP is an early event in the 
      human diabetic retina and is associated with retinal neurodegeneration. The 
      mechanisms leading to this deficit deserve further investigation.
FAU - Garcia-Ramirez, M
AU  - Garcia-Ramirez M
AD  - CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM), Diabetes and 
      Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall 
      d'Hebron, Universitat Autonoma de Barcelona Pg. Vall d'Hebron 119-129, 08035, 
      Barcelona, Spain.
FAU - Hernandez, C
AU  - Hernandez C
FAU - Villarroel, M
AU  - Villarroel M
FAU - Canals, F
AU  - Canals F
FAU - Alonso, M A
AU  - Alonso MA
FAU - Fortuny, R
AU  - Fortuny R
FAU - Masmiquel, L
AU  - Masmiquel L
FAU - Navarro, A
AU  - Navarro A
FAU - Garcia-Arumi, J
AU  - Garcia-Arumi J
FAU - Simo, R
AU  - Simo R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091013
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Eye Proteins)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (RNA, Messenger)
RN  - 0 (Retinol-Binding Proteins)
RN  - 0 (interstitial retinol-binding protein)
SB  - IM
MH  - Age of Onset
MH  - Aged
MH  - Apoptosis
MH  - Diabetic Retinopathy/*genetics/metabolism/pathology
MH  - Down-Regulation
MH  - Eye Proteins/*genetics/metabolism
MH  - Female
MH  - Gene Amplification
MH  - Genes, Retinoblastoma/genetics
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Humans
MH  - Male
MH  - Microscopy, Confocal/methods
MH  - Middle Aged
MH  - Photoreceptor Cells, Vertebrate/*metabolism
MH  - RNA, Messenger/genetics
MH  - Retinal Neoplasms/genetics/pathology
MH  - Retinal Perforations/genetics/metabolism/pathology
MH  - Retinoblastoma/genetics/pathology
MH  - Retinol-Binding Proteins/*genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vitreous Body/metabolism
EDAT- 2009/10/14 06:00
MHDA- 2010/04/24 06:00
CRDT- 2009/10/14 06:00
PHST- 2009/07/27 00:00 [received]
PHST- 2009/09/02 00:00 [accepted]
PHST- 2009/10/14 06:00 [entrez]
PHST- 2009/10/14 06:00 [pubmed]
PHST- 2010/04/24 06:00 [medline]
AID - 10.1007/s00125-009-1548-8 [doi]
PST - ppublish
SO  - Diabetologia. 2009 Dec;52(12):2633-41. doi: 10.1007/s00125-009-1548-8. Epub 2009 
      Oct 13.