Formation of hydroxyl radicals in the human lens is related to the severity of nuclear cataract
Research output: Contribution to journal › Journal article › peer-review
Standard
Formation of hydroxyl radicals in the human lens is related to the severity of nuclear cataract. / Garner, B; Davies, Michael Jonathan; Truscott, R J.
In: Experimental Eye Research, Vol. 70, No. 1, 01.2000, p. 81-8.Research output: Contribution to journal › Journal article › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Formation of hydroxyl radicals in the human lens is related to the severity of nuclear cataract
AU - Garner, B
AU - Davies, Michael Jonathan
AU - Truscott, R J
N1 - Copyright 2000 Academic Press.
PY - 2000/1
Y1 - 2000/1
N2 - Recent studies have identified specific hydroxylated amino acid oxidation products which strongly suggest the presence of hydroxyl radical (HO.)-damaged proteins in human cataractous lenses. In the present study, the ability of early stage (type II) and advanced (type IV) nuclear cataractous lens homogenates to catalyse HO. production in the presence of H(2)O(2)was investigated using electron paramagnetic resonance (EPR) spectroscopy with the free radical trap, 5,5-dimethyl-1-pyrroline- N -oxide (DMPO). Cataractous lens homogenates incubated with 1 m m H(2)O(2)generated a distinct HO. signal, which was significantly more intense in the nuclear region of the type IV compared to the type II lenses. The ability of individual lens nuclei and cortices to stimulate HO. production was positively correlated. The DMPO-HO. signal was competitively inhibited by ethanol, confirming that the DMPO-HO. signal was due to HO. formation and not DMPO-OOH degradation. The metal ion chelator, diethylenetriaminepentaacetic acid, also inhibited HO. formation, indicating that lenticular metal ions play a key role in HO. formation. Cataractous lens homogenates also stimulated ascorbyl radical production, further suggesting the presence of redox-active metal ions in the tissue. Analysis of lenses for total Fe and Cu (using atomic absorption spectrometry) showed that the more advanced type IV lenses tended to have higher Fe, but similar Cu, levels compared to the type II lenses. The levels of both metals were lower in non-cataractous lenses. These data support the hypothesis that transition metal-mediated HO. production may play a role in the aetiology of age-related nuclear cataract.
AB - Recent studies have identified specific hydroxylated amino acid oxidation products which strongly suggest the presence of hydroxyl radical (HO.)-damaged proteins in human cataractous lenses. In the present study, the ability of early stage (type II) and advanced (type IV) nuclear cataractous lens homogenates to catalyse HO. production in the presence of H(2)O(2)was investigated using electron paramagnetic resonance (EPR) spectroscopy with the free radical trap, 5,5-dimethyl-1-pyrroline- N -oxide (DMPO). Cataractous lens homogenates incubated with 1 m m H(2)O(2)generated a distinct HO. signal, which was significantly more intense in the nuclear region of the type IV compared to the type II lenses. The ability of individual lens nuclei and cortices to stimulate HO. production was positively correlated. The DMPO-HO. signal was competitively inhibited by ethanol, confirming that the DMPO-HO. signal was due to HO. formation and not DMPO-OOH degradation. The metal ion chelator, diethylenetriaminepentaacetic acid, also inhibited HO. formation, indicating that lenticular metal ions play a key role in HO. formation. Cataractous lens homogenates also stimulated ascorbyl radical production, further suggesting the presence of redox-active metal ions in the tissue. Analysis of lenses for total Fe and Cu (using atomic absorption spectrometry) showed that the more advanced type IV lenses tended to have higher Fe, but similar Cu, levels compared to the type II lenses. The levels of both metals were lower in non-cataractous lenses. These data support the hypothesis that transition metal-mediated HO. production may play a role in the aetiology of age-related nuclear cataract.
KW - Ascorbic Acid
KW - Cataract
KW - Copper
KW - Humans
KW - Hydrogen Peroxide
KW - Hydroxyl Radical
KW - Iron
KW - Lens, Crystalline
KW - Oxidation-Reduction
KW - Spectrophotometry, Atomic
U2 - 10.1006/exer.1999.0754
DO - 10.1006/exer.1999.0754
M3 - Journal article
C2 - 10644423
VL - 70
SP - 81
EP - 88
JO - Experimental Eye Research
JF - Experimental Eye Research
SN - 0014-4835
IS - 1
ER -
ID: 138281859