PMID- 23335850
OWN - NLM
STAT- MEDLINE
DCOM- 20130906
LR  - 20220410
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 19
DP  - 2013
TI  - Proapoptotic and survival signaling in the neuroretina at early stages of 
      diabetic retinopathy.
PG  - 47-53
AB  - PURPOSE: Diabetic retinopathy (DR) has been classically considered a 
      microcirculatory disease of the retina. However, before any microcirculatory 
      abnormalities can be detected in ophthalmoscopic examination, retinal 
      neurodegeneration is already present. The aim of the study was to analyze 
      proapoptotic and survival signaling in the neuroretinas of diabetic patients at 
      early stages of DR. METHODS: The retinas from five diabetic donors at early 
      stages of DR were compared with the retinas from five nondiabetic donors matched 
      by age. Glial activation was evaluated by assessing glial fibrillar acidic 
      protein (GFAP) with western blot and immunofluorescence. Proapoptotic molecules 
      (FasL, procaspase-8, active caspase-8, total Bid, truncated Bid, Bim, and active 
      caspase-3), as well as antiapoptotic markers (FLIP, BclxL, and cyclooxygenase-2 
      [COX-2]) were assessed with western blot. RESULTS: GFAP and proapoptotic 
      molecules (FasL, active caspase-8, truncated Bid (t-Bid), Bim, and active 
      caspase-3) were significantly increased in the neuroretinas from diabetic 
      patients compared to the control neuroretinas. In contrast, no significant 
      differences in the expression of the antiapoptotic markers were found. 
      CONCLUSIONS: An imbalance between proapoptotic and survival signaling was found 
      in diabetic neuroretinas. Our results reveal key mechanistic pathways involved in 
      the neurodegenerative process that occurs in the early stages of DR.
FAU - Valverde, Angela M
AU  - Valverde AM
AD  - Instituto de Investigaciones Biomedicas Alberto Sols (CSIC/UAM), Madrid, Spain. 
      avalverde@iib.uam.es
FAU - Miranda, Soledad
AU  - Miranda S
FAU - Garcia-Ramirez, Marta
AU  - Garcia-Ramirez M
FAU - Gonzalez-Rodriguez, Agueda
AU  - Gonzalez-Rodriguez A
FAU - Hernandez, Cristina
AU  - Hernandez C
FAU - Simo, Rafael
AU  - Simo R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130107
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (BH3 Interacting Domain Death Agonist Protein)
RN  - 0 (BID protein, human)
RN  - 0 (Biomarkers)
RN  - 0 (FASLG protein, human)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Aged
MH  - Apoptosis/*physiology
MH  - BH3 Interacting Domain Death Agonist Protein/metabolism
MH  - Biomarkers/metabolism
MH  - Case-Control Studies
MH  - Caspase 3/metabolism
MH  - Caspase 8/metabolism
MH  - Cell Survival/*physiology
MH  - Diabetic Retinopathy/etiology/*metabolism/*pathology
MH  - Fas Ligand Protein/metabolism
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Humans
MH  - Middle Aged
MH  - Nerve Degeneration/etiology/metabolism/pathology
MH  - Retina/*metabolism/*pathology
MH  - Signal Transduction/physiology
PMC - PMC3541044
EDAT- 2013/01/22 06:00
MHDA- 2013/09/07 06:00
PMCR- 2013/01/01
CRDT- 2013/01/22 06:00
PHST- 2012/04/24 00:00 [received]
PHST- 2013/01/04 00:00 [accepted]
PHST- 2013/01/22 06:00 [entrez]
PHST- 2013/01/22 06:00 [pubmed]
PHST- 2013/09/07 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 5 [pii]
PST - ppublish
SO  - Mol Vis. 2013;19:47-53. Epub 2013 Jan 7.