PMID- 15505070
OWN - NLM
STAT- MEDLINE
DCOM- 20041208
LR  - 20240109
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 45
IP  - 11
DP  - 2004 Nov
TI  - Role of interleukin-1beta in the development of retinopathy in rats: effect of 
      antioxidants.
PG  - 4161-6
AB  - PURPOSE: Diabetic retinopathy is shown to share many similarities with chronic 
      inflammatory disease, and in diabetes, accelerated apoptosis of retinal capillary 
      cells is evident before histopathology can be seen. The purpose of this study was 
      to examine the effect of interleukin (IL)-1beta on capillary cell apoptosis in 
      rat retina and to determine the effect of antioxidants on diabetes-induced 
      changes in retinal IL-1beta. METHODS: The effect of injection of IL-1beta into 
      the vitreous (5 ng/5 microL) of normal rats on capillary cell apoptosis (detected 
      by terminal transferase dUTP nick-end labeling [TUNEL]) and formation of 
      acellular capillaries was investigated in the trypsin digested retinal 
      microvessels. The levels of IL-1beta were quantified (by ELISA and Western blot) 
      in the retina of rats diabetic for 2 months, and the effect of administration of 
      antioxidants on diabetes-induced changes in retinal IL-1beta was determined. 
      RESULTS: The number of TUNEL-positive capillary cells in the retinal microvessels 
      obtained from normal rats that received intravitreal injection of IL-1beta was 
      increased by more than threefold and that of acellular capillaries by more than 
      twofold, compared with the microvessels obtained from rats that received an 
      intravitreal injection of PBS (5 microL) or BSA (5 ng/5 microL). IL-1beta also 
      increased the levels of 8-hydroxy-2'-deoxyguanosine (an indicator of oxidative 
      stress) and nitric oxide by more than 40% and activated NF-kappaB by 35% to 55%. 
      Two months of diabetes in rats increased retinal IL-1beta levels by more than 
      twofold, and antioxidants inhibited such increases. CONCLUSIONS: IL-1beta, by 
      activation of NF-kappaB and an increase in oxidative stress, plays an important 
      role in the retinal microvascular disease that is characteristic of diabetic 
      retinopathy. Antioxidants inhibit diabetes-induced increases in retinal IL-1beta. 
      These studies offer a possible rationale to test IL-1beta-targeted therapies to 
      inhibit the development of retinopathy in diabetes.
FAU - Kowluru, Renu A
AU  - Kowluru RA
AD  - Kresge Eye Institute, Wayne State University, Detroit, Michigan 48201, USA. 
      rkowluru@med.wayne.edu
FAU - Odenbach, Sarah
AU  - Odenbach S
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 (Antioxidants)
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)
RN  - G9481N71RO (Deoxyguanosine)
SB  - IM
MH  - 8-Hydroxy-2'-Deoxyguanosine
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Capillaries
MH  - Deoxyguanosine/*analogs & derivatives/metabolism
MH  - Diabetes Mellitus, Experimental/metabolism/pathology/*prevention & control
MH  - Diabetic Retinopathy/metabolism/pathology/*prevention & control
MH  - Enzyme-Linked Immunosorbent Assay
MH  - In Situ Nick-End Labeling
MH  - Interleukin-1/pharmacology/*physiology
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/metabolism
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Retinal Vessels/*drug effects/pathology
EDAT- 2004/10/27 09:00
MHDA- 2004/12/16 09:00
CRDT- 2004/10/27 09:00
PHST- 2004/10/27 09:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/10/27 09:00 [entrez]
AID - 45/11/4161 [pii]
AID - 10.1167/iovs.04-0633 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2004 Nov;45(11):4161-6. doi: 10.1167/iovs.04-0633.