Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in Aldh3a1(-/-)/Aldh1a1(-/-) knock-out mice.
ALDH3A1 (aldehyde dehydrogenase 3A1) is abundant in the mouse cornea but undetectable in the lens, and ALDH1A1 is present at lower (catalytic) levels in the cornea and lens. To test the hypothesis that ALDH3A1 and ALDH1A1 protect the anterior segment of the eye against environmentally induced oxidative damage, Aldh1a1(-/-)/Aldh3a1(-/-) double knock-out and Aldh1a1(-/-) and Aldh3a1(-/-) single knock-out mice were evaluated for biochemical changes and cataract formation (lens opacification). The Aldh1a1/Aldh3a1- and Aldh3a1-null mice develop cataracts in the anterior and posterior subcapsular regions as well as punctate opacities in the cortex by 1 month of age. The Aldh1a1-null mice also develop cataracts later in life (6-9 months of age). One- to three-month-old Aldh-null mice exposed to UVB exhibited accelerated anterior lens subcapsular opacification, which was more pronounced in Aldh3a1(-/-) and Aldh3a1(-/-)/Aldh1a1(-/-) mice compared with Aldh1a1(-/-) and wild type animals. Cataract formation was associated with decreased proteasomal activity, increased protein oxidation, increased GSH levels, and increased levels of 4-hydroxy-2-nonenal- and malondialdehyde-protein adducts. In conclusion, these findings support the hypothesis that corneal ALDH3A1 and lens ALDH1A1 protect the eye against cataract formation via nonenzymatic (light filtering) and enzymatic (detoxification) functions.
Lassen
Natalie
N
Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, Rocky Mountain Lions Eye Institute, The Children's Hospital, University of Colorado, Denver, Colorado 80262, USA.
Bateman
J Bronwyn
JB
Estey
Tia
T
Kuszak
Jer R
JR
Nees
David W
DW
Piatigorsky
Joram
J
Duester
Gregg
G
Day
Brian J
BJ
Huang
Jie
J
Hines
Lisa M
LM
Vasiliou
Vasilis
V
D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000444:Aldehyde Dehydrogenase / Q000172:deficiency / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D002386:Cataract / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D003315:Cornea / Q000201:enzymology* / Q000473:pathology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D007908:Lens, Crystalline / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction / Q000528:radiation effects; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D050697:Retinal Dehydrogenase; D014466:Ultraviolet Rays / Q000009:adverse effects
D000444:Aldehyde Dehydrogenase; D000080924:Aldehyde Dehydrogenase 1 Family; D005136:Eye Proteins; D005978:Glutathione; D046988:Proteasome Endopeptidase Complex; D050697:Retinal Dehydrogenase; C105543:Aldh3a1 protein, mouse; C515028:ALDH1A1 protein, mouse