PMID- 16799061
OWN - NLM
STAT- MEDLINE
DCOM- 20060807
LR  - 20220317
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 47
IP  - 7
DP  - 2006 Jul
TI  - Loss of cholinergic and dopaminergic amacrine cells in streptozotocin-diabetic 
      rat and Ins2Akita-diabetic mouse retinas.
PG  - 3143-50
AB  - PURPOSE: To identify amacrine cells that are vulnerable to degeneration during 
      the early stages of diabetes. METHODS: Whole retinas from streptozotocin 
      (STZ)-diabetic rats and Ins2(Akita) mice were fixed in paraformaldehyde. 
      Apoptotic cells in the retina were quantified using terminal dUTP nick-end 
      labeling (TUNEL) and active caspase-3 (CM-1) immunohistochemistry. 
      Immunohistochemical markers for choline acetyltransferase (ChAT) and tyrosine 
      hyroxylase (TH) were also used to quantify populations of amacrine cells in the 
      Ins2Akita mouse retinas. RESULTS: The number of TUNEL-positive nuclei increased 
      from 29+/-4 in controls to 72+/-9 in the STZ-diabetic rat retinas after only 2 
      weeks of diabetes. In rats, CM-1-immunoreactive (IR) cells were found primarily 
      in the inner nuclear and ganglion cell layers after 2, 8, and 16 weeks of 
      diabetes. At each end point, the number of CM-1-IR cells in the retina was 
      elevated by diabetes. Approximately 2% to 6% of the CM-1-IR cells in the inner 
      nuclear layer (INL) were double-labeled for TH immunoreactivity. After 6 months 
      of diabetes in the Ins2Akita mouse, the morphology of the labeled ChAT-IR and 
      TH-IR amacrine cell somas and dendrites appeared normal. A quantitative analysis 
      revealed a 20% decrease in the number of cholinergic and a 16% decrease in 
      dopaminergic amacrine cells in the diabetic mouse retinas, compared with the 
      nondiabetic control. CONCLUSIONS: Dopaminergic and cholinergic amacrine cells are 
      lost during the early stages of retinal neuropathy in diabetes. Loss of these 
      neurons may play a critical role in the development of visual deficits in 
      diabetes.
FAU - Gastinger, Matthew J
AU  - Gastinger MJ
AD  - Milton S. Hershey Medical Center, Penn State Retina Research Group, Ulrich 
      Ophthalmology Research Laboratory, Pennsylvania State College of Medicine, 
      Hershey, Pennsylvania 17033, USA.
FAU - Singh, Ravi S J
AU  - Singh RS
FAU - Barber, Alistair J
AU  - Barber AJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (Receptors, Dopamine)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 2.3.1.6 (Choline O-Acetyltransferase)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amacrine Cells/metabolism/*pathology
MH  - Animals
MH  - *Apoptosis
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cell Count
MH  - Choline O-Acetyltransferase/metabolism
MH  - Diabetes Mellitus, Experimental/metabolism/*pathology
MH  - Diabetic Retinopathy/metabolism/*pathology
MH  - Fluorescent Antibody Technique, Indirect
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Confocal
MH  - Neurons/metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Cholinergic/*metabolism
MH  - Receptors, Dopamine/*metabolism
MH  - Retinal Degeneration/metabolism/*pathology
MH  - Tyrosine 3-Monooxygenase/metabolism
EDAT- 2006/06/27 09:00
MHDA- 2006/08/08 09:00
CRDT- 2006/06/27 09:00
PHST- 2006/06/27 09:00 [pubmed]
PHST- 2006/08/08 09:00 [medline]
PHST- 2006/06/27 09:00 [entrez]
AID - 47/7/3143 [pii]
AID - 10.1167/iovs.05-1376 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2006 Jul;47(7):3143-50. doi: 10.1167/iovs.05-1376.