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Steven L. Bernstein, Anna M.-H. Liu, Barbara C. Hansen, Richard Idem Somiari; Heat Shock Cognate-70 Gene Expression Declines during Normal Aging of the Primate Retina. Invest. Ophthalmol. Vis. Sci. 2000;41(10):2857-2862.
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purpose. Despite documented age-related changes in retinal function and
histology, little is known about the pattern of gene expression during
normal aging of the vertebrate retina. This study was undertaken to
definitively characterize gene expression in the primate retina during
methods. Human retina cDNA library clones were arrayed at high density on nylon
membranes and screened with mixed cDNA probes generated from young
(4-year-old) and old (80-year-old) human retinae. Clones showing a more
than twofold difference in intensity were rescreened by dot blot
analysis with the same probes and with mixed cDNA probes generated from
young (2–3 years) and old (27–35 years) rhesus monkeys. One clone
identified by its differential (age-putative) signal, and age-related
differential expression was used for analysis of Northern blot analysis
of total retinal RNA from human donors (35 weeks to 94 years of age)
and two rhesus monkeys (2 and 27 years of age). The identified clone
was sequenced and compared with entries in the GenBank/EMBL databases.
Western blot analysis was performed on protein isolated from the retina
of human donors aged 4 to 64 years and rhesus monkeys aged 18 months
and 35 years.
results. Approximately 1.6% of the 55,368 retina-expressed sequences examined
show age-related changes between tissues from young and old donors. The
mRNA level one clone, identical with heat shock cognate (HSC)70, was
altered during normal retinal aging in primates. Regression analysis of
Northern blot analysis signals from 23 human donors suggested that
there may be a two- to threefold decrease in HSC70 mRNA levels in the
human retina by the eighth decade of life. Western blot analysis also
showed lower levels of the 70-kDa HSC protein in older tissues of both
conclusions. HSC70 mRNA levels apparently decline during normal aging of the primate
retina. Because the heat shock 70 protein family may play important
roles in ocular development and protection from various biologic and
environmental stresses, decreased HSC70 levels in the retina during
aging may contribute to the apparent increased susceptibility of the
retina to age-acquired retinal disease.
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