title: Age-related differences in signaling efficiency of human lens cells underpin differential wound healing response rates following cataract surgery.
abstract: OBJECTIVE
  Cataract surgery is blighted by posterior capsule opacification (PCO), which is more severe and frequent in the young than the elderly (>60 years). Our aim was to understand the biological basis for these age-related differences in PCO/wound healing rates.
  
  
  METHODS
  Human capsular bags were prepared by cataract surgery on donor lenses (young [<40 years] and elderly [>60 years] groups) and maintained in serum-free Eagle's minimum essential medium. Cell growth was determined using the MTS assay. Fibroblast growth factor (FGF) and hepatocyte growth factor (HGF) levels were determined using ELISA. Protein synthesis rates were elucidated by 35S-methionine incorporation. U0126, SB203580, and SP600125 were used to disrupt ERK-, p38-, and JNK-mediated signaling, respectively. Level of total and phospho-ERK, -c-jun, -P38, and -JNK plus cytokines were detected using a BIOPLEX array system.
  
  
  RESULTS
  Following a 2-day culture period, significant decreases in IL-1β and IL-6, and increases in IL-10, IL-12, IL-13, and VEGF in the >60 years group were observed compared with their younger counterparts. Capsular bags (cells and capsule) from aged donors contained greater than or equal levels of HGF and FGF than younger counterparts and had greater rates of protein synthesis. Inhibition of ERK, p38, and JNK signaling significantly suppressed cell coverage on the posterior capsule. pERK, p-c-jun, p-p38, and pJNK were consistently lower in aged cell populations; total signaling protein expression was unaffected by age. Serum stimulation increased pERK, p-c-jun, and pJNK levels in cells of all ages; p-p38 was significantly increased in the >60 years group only.
  
  
  CONCLUSIONS
  Ligand availability to cells is not a limiting factor as we age, but the ability to convert this resource into signaling activity is. We therefore propose that overall signaling efficiency is reduced as a function of age, which consequently limits wound-healing response rates after injury.
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich, United Kingdom.
authors.forename: Lucy Jean
authors.initials: LJ
authors.lastname: Dawes
authors.forename: George
authors.initials: G
authors.lastname: Duncan
authors.forename: Ian Michael
authors.initials: IM
authors.lastname: Wormstone
mesh_terms: D000328:Adult; D000375:Aging / Q000473:pathology*; D002386:Cataract / Q000378:metabolism* / Q000473:pathology; D002387:Cataract Extraction; D049109:Cell Proliferation; D002478:Cells, Cultured; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D015398:Signal Transduction; D014945:Wound Healing
chemical_list: D007378:Interleukins; D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor