PURPOSE: In young Swiss (HSD:ICR) outbred mice, corneal clarity is restored after Pseudomonas aeruginosa ocular infection, whereas disease in aged outbred mice progresses to corneal perforation. This study was conducted to elucidate further the mechanism responsible for this age-related disparity in disease response. METHODS: Corneas of young (6 to 8 weeks of age) and aged (1.5 to 2 years) female mice were scarified and inoculated with 1.0 x 10(8) colony-forming units of P. aeruginosa ATCC 19660. Eyes were scored for corneal pathology (0 to +4) at 6, 12, 24, 48, 72, 96, and 120 hours after infection. At each time point, six mice were killed from each age group, and both eyes were enucleated. Eyes (three infected, three uninfected) were embedded in OCT compound, frozen in liquid nitrogen, sectioned on a cryostat, and stained for ICAM-1 and LFA-1 immunoreactivity. The remaining six eyes (three infected, three uninfected) were embedded in eponaraldite resin, thick sectioned, and stained for light microscopic histopathologic examination. RESULTS: Immunostaining of slight to moderate intensity for ICAM-1 was seen on conjunctival fibroblasts, stromal keratocytes, corneal epithelium, and endothelium and conjunctival blood vessel endothelium of uninfected contralateral eyes in both age groups. In response to P. aeruginosa infection, only young animals were capable of upregulating ICAM-1 (as evidenced by an increase in the intensity of immunostaining) on these cells when compared to aged mice. Conversely, the intensity of immunostaining for LFA-1, a ligand for ICAM-1 on infiltrating leukocytes, was similar despite animal age. On gross observation, corneal pathology was more severe in young mice 24 to 96 hours after infection. Histopathologically, in contrast to young mice, eyes of aged animals 24 to 48 hours after infection had significantly fewer inflammatory cells, such as polymorphonuclear leukocytes (PMNs), infiltrating the corneal stroma and adhering to the endothelium near wound sites. CONCLUSION: These data suggest that the disparate response to ocular P. aeruginosa infection in young versus aged mice is due, at least in part, to the inability of aged animals to upregulate ICAM-1 above constitutively expressed levels. Consequently, the migration of inflammatory cells (PMNs) into infected corneas of aged mice is delayed, perhaps facilitating bacterial growth and contributing to a poor prognosis.
PURPOSE: In young Swiss (HSD:ICR) outbred mice, corneal clarity is restored after Pseudomonas aeruginosa ocular infection, whereas disease in aged outbred mice progresses to corneal perforation. This study was conducted to elucidate further the mechanism responsible for this age-related disparity in disease response. METHODS: Corneas of young (6 to 8 weeks of age) and aged (1.5 to 2 years) female mice were scarified and inoculated with 1.0 x 10(8) colony-forming units of P. aeruginosa ATCC 19660. Eyes were scored for corneal pathology (0 to +4) at 6, 12, 24, 48, 72, 96, and 120 hours after infection. At each time point, six mice were killed from each age group, and both eyes were enucleated. Eyes (three infected, three uninfected) were embedded in OCT compound, frozen in liquid nitrogen, sectioned on a cryostat, and stained for ICAM-1 and LFA-1 immunoreactivity. The remaining six eyes (three infected, three uninfected) were embedded in eponaraldite resin, thick sectioned, and stained for light microscopic histopathologic examination. RESULTS: Immunostaining of slight to moderate intensity for ICAM-1 was seen on conjunctival fibroblasts, stromal keratocytes, corneal epithelium, and endothelium and conjunctival blood vessel endothelium of uninfected contralateral eyes in both age groups. In response to P. aeruginosa infection, only young animals were capable of upregulating ICAM-1 (as evidenced by an increase in the intensity of immunostaining) on these cells when compared to aged mice. Conversely, the intensity of immunostaining for LFA-1, a ligand for ICAM-1 on infiltrating leukocytes, was similar despite animal age. On gross observation, corneal pathology was more severe in young mice 24 to 96 hours after infection. Histopathologically, in contrast to young mice, eyes of aged animals 24 to 48 hours after infection had significantly fewer inflammatory cells, such as polymorphonuclear leukocytes (PMNs), infiltrating the corneal stroma and adhering to the endothelium near wound sites. CONCLUSION: These data suggest that the disparate response to ocular P. aeruginosa infection in young versus aged mice is due, at least in part, to the inability of aged animals to upregulate ICAM-1 above constitutively expressed levels. Consequently, the migration of inflammatory cells (PMNs) into infected corneas of aged mice is delayed, perhaps facilitating bacterial growth and contributing to a poor prognosis.
Authors: Debjani Gagen; Sara Laubinger; Zhijie Li; Matei S Petrescu; Evelyn S Brown; C Wayne Smith; Alan R Burns Journal: Exp Eye Res Date: 2010-08-14 Impact factor: 3.467
Authors: Margarete Johnson; Jessica Lloyd; Srinivas Tekkam; Stephen N Crooke; Deborah A Witherden; Wendy L Havran; M G Finn Journal: ACS Appl Bio Mater Date: 2020-07-18
Authors: Ling C Huang; Rachel L Redfern; Srihari Narayanan; Rose Y Reins; Alison M McDermott Journal: Antimicrob Agents Chemother Date: 2007-08-27 Impact factor: 5.191