title: Distinct signature of altered homeostasis in aging rod photoreceptors: implications for retinal diseases.
abstract: BACKGROUND
  Advanced age contributes to clinical manifestations of many retinopathies and represents a major risk factor for age-related macular degeneration, a leading cause of visual impairment and blindness in the elderly. Rod photoreceptors are especially vulnerable to genetic defects and changes in microenvironment, and are among the first neurons to die in normal aging and in many retinal degenerative diseases. The molecular mechanisms underlying rod photoreceptor vulnerability and potential biomarkers of the aging process in this highly specialized cell type are unknown.
  
  
  RESULTS
  To discover aging-associated adaptations that may influence rod function, we have generated gene expression profiles of purified rod photoreceptors from mouse retina at young adult to early stages of aging (1.5, 5, and 12 month old mice). We identified 375 genes that showed differential expression in rods from 5 and 12 month old mouse retina compared to that of 1.5 month old retina. Quantitative RT-PCR experiments validated expression change for a majority of the 25 genes that were examined. Macroanalysis of differentially expressed genes using gene class testing and protein interaction networks revealed overrepresentation of cellular pathways that are potentially photoreceptor-specific (angiogenesis and lipid/retinoid metabolism), in addition to age-related pathways previously described in several tissue types (oxidative phosphorylation, stress and immune response).
  
  
  CONCLUSIONS
  Our study suggests a progressive shift in cellular homeostasis that may underlie aging-associated functional decline in rod photoreceptors and contribute to a more permissive state for pathological processes involved in retinal diseases.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Parapuram
authors.forename: Radu I
authors.initials: RI
authors.lastname: Cojocaru
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Chang
authors.forename: Ritu
authors.initials: R
authors.lastname: Khanna
authors.forename: Matthew
authors.initials: M
authors.lastname: Brooks
authors.forename: Mohammad
authors.initials: M
authors.lastname: Othman
authors.forename: Sepideh
authors.initials: S
authors.lastname: Zareparsi
authors.forename: Naheed W
authors.initials: NW
authors.lastname: Khan
authors.forename: Norimoto
authors.initials: N
authors.lastname: Gotoh
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cogliati
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
mesh_terms: D000375:Aging; D000818:Animals; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012160:Retina / Q000254:growth & development / Q000378:metabolism; D012164:Retinal Diseases / Q000235:genetics; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors