Microarray analysis of gene expression in the aging human retina.
OBJECTIVE
To develop gene expression profiles of young and elderly human retinas and identify candidate genes for aging-associated retinal diseases.


METHODS
Gene microarray slides containing 2400 human genes (primarily neuronal) were hybridized to biotin or dinitrophenyl (DNP)-labeled target cDNAs that were synthesized using total RNAs from young (13-14 years) and elderly (62-74 years) human retinas. Hybridization signals were visualized with cyanine (Cy)-5 or Cy-3 fluorescent reporter molecules, and the fluorescence intensities of the images were analyzed by computer. Northern blot analysis and real-time quantitative reverse transcription PCR (qRT-PCR) were performed to validate the microarray results.


RESULTS
Of the 2400 genes represented on the microarray slides, more than 50% hybridized to the retinal cDNA targets. Expression of a majority of these genes was not altered during aging; nonetheless, changes in the expression of 24 genes were detected between young and elderly retinas. These genes could be clustered into four categories: energy metabolism, stress response, cell growth, and neuronal transmission/signaling. Northern blot analysis and qRT-PCR results confirmed the changes in expression of 8 of 10 genes examined.


CONCLUSIONS
Using commercially available slide microarrays, the authors show that aging of the human retina is associated with changes in patterns of gene expression. This analysis suggests that pathways involved in stress response and energy metabolism play key roles in retinal aging. These studies demonstrate the utility of gene microarrays in identifying global patterns of retinal gene expression and lay the foundation for future studies defining the genetic basis of aging-associated retinal diseases, such as age-related macular degeneration.
Yoshida
Shigeo
S
Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan 48105, USA.
Yashar
Beverly M
BM
Hiriyanna
Suja
S
Swaroop
Anand
A
D000293:Adolescent; D000368:Aged; D000375:Aging / Q000502:physiology*; D015152:Blotting, Northern; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012160:Retina / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005136:Eye Proteins