Localization of low molecular weight crystallin peptides in the aging human lens using a MALDI mass spectrometry imaging approach.
Low molecular weight (LMW) peptides, derived from the breakdown of the major eye lens proteins, the crystallins, accumulate in the human lens with age. These LMW peptides are associated with age-related lens opacity and cataract, with some shown to inhibit the chaperone activity of alpha-crystallin. However, the mechanism(s) giving rise to the production of these peptides, as well as their distribution within the lens, are not well understood. In this study, we have mapped the distribution of these crystallin-derived peptides present in human lenses of different ages using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Our data showed that most of these LMW peptides emerge in the lens at early middle-age, with peptides greater than 1778 Da in mass being confined to the water insoluble fractions, and to a lesser extent the water soluble fractions of older lenses. MALDI-IMS analyses showed that four peptides, derived from alphaA-, alphaB- and gammaS-crystallins, were confined to the lens nuclear fibre cells upon emergence during early middle-age, but were present in both the cortex and nucleus of old lenses. In contrast, another major peptide, derived from the C-terminal breakdown of betaA3-crystallin, was present in the cortical and nuclear regions of both young and old lenses. A comparison between age-matched cataractous and non-cataractous lenses showed no distinct differences in LMW peptide profiles, indicating that although cataract may be a potential consequence caused by the emergence of these peptides, it does not contribute directly to the peptide-generating process.
Su
Shih-Ping
SP
School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.
McArthur
Jason D
JD
Andrew Aquilina
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D002386:Cataract / Q000378:metabolism*; D003459:Crystallins / Q000378:metabolism*; D006801:Humans; D007904:Lens Cortex, Crystalline / Q000378:metabolism*; D007907:Lens Nucleus, Crystalline / Q000378:metabolism*; D008875:Middle Aged; D008970:Molecular Weight; D010446:Peptide Fragments / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
D003459:Crystallins; D010446:Peptide Fragments