Cataracts are a major cause of
blindness worldwide and commonly occur in individuals over 70 years old.
Cataracts can also appear earlier in life due to genetic mutations. The
lens proteins, αA- and αB-
crystallins, are chaperone
proteins that have important roles maintaining
protein solubility to prevent
cataract formation. Mutations in the CRYAA and CRYAB
crystallin genes are associated with autosomal dominant early onset human
cataracts. Although studies about the proteomic and genomic changes that occur in
cataracts have been reported, metabolomics studies are very limited. Here, we directly investigated
cataract metabolism using gas-chromatography-mass spectrometry (GC-MS) to analyze the metabolites in adult Cryaa-R49C and Cryab-R120G knock-in mouse
lenses. The most abundant metabolites were myo-
inositol,
L-(+)-lactic acid,
cholesterol, phosphate,
glycerol phosphate, palmitic and 9-octadecenoic
acids, α-D-
mannopyranose, and β-D-glucopyranose. Cryaa-R49C knock-in mouse
lenses had a significant decrease in the number of
sugars and minor
sterols, which occurred in concert with an increase in
lactic acid.
Cholesterol composition was unchanged. In contrast, Cryab-R120G knock-in
lenses exhibited increased total
amino acid content including
valine,
alanine,
serine,
leucine,
isoleucine,
glycine, and
aspartic acid. Minor
sterols, including
cholest-7-en-3-ol and
glycerol phosphate were decreased. These studies indicate that
lenses from Cryaa-R49C and Cryab-R120G knock-in mice, which are models for human
cataracts, have unique
amino acid and metabolite profiles.