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Jay Ching-Chieh Wang, Sijia Cao, Aikun Wang, Jing Cui, Joanne Matsubara; Inflammatory cytokines in the vitreous of postmortem eyes: Relationship to age and drusen load. Invest. Ophthalmol. Vis. Sci. 2013;54(15):142. doi: https://doi.org/.
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Recent studies provide evidence that chronic local inflammation plays an important role in the pathogenesis of age-related macular degeneration (AMD). While aging, drusen load and complement factor H (CFH) polymorphism increase AMD risk, their relationships to the local inflammatory processes in the eye require further investigation. We examined the level of inflammatory cytokines (ICs) and growth factors (GFs) in the vitreous of post-mortem donor eyes and their relationship to age, drusen load and single nucleotide polymorphisms for the CFH (Y402H) at risk variant (T>C).
Sixteen pairs of post-mortem human donor eyes, with average time from death to tissue processing of 15.14 hr (SD±4.7 hr), were used in this study. To assess the effect of postmortem time on cytokine degradation, vitreous samples from Long Evans rats were collected at 0, 10 and 20 hrs after sacrifice and examined with multiplex suspension arrays (BioplexTM). In processing the human postmortem eyes, the right eyes were embedded in paraffin to assess for drusen load; the left eyes were dissected circumferentially at the pars plana for collection of vitreous. Retinal tissues were used to genotype for CFH Y402H polymorphism. The vitreous samples were analyzed for ICs and GFs using BioplexTM. Cytokine concentrations were compared between two groups: younger (≤55 year-old) vs older (≥70 year-old) eyes and drusen vs no drusen eyes. A fold change (FC) of ≥2 was set as cutoff. Data were analyzed by Student’s t test.
Rat vitreous IC and GF levels are higher at 0 hr, but do not change significantly between 10 and 20 hrs after sacrifice. In the human vitreous, IL-13 showed a FC of 2.6 between eyes with and without drusen (p<0.05), while VEGF, IL-6 and IL-10 showed marginally significant FCs of 3.6, 3.0 and 2.0, respectively (p<0.15); this was independent of age. Based on age, IP-10, MCP-1 and IL-8 were higher in older eyes than younger eyes with FCs of 3.7, 3.1, and 3.1, respectively (p<0.05). Comparisons were also made based on CFH Y402H genotypes (CC VS TT).
Post-mortem eyes are valuable materials to assess effects of age, drusen load and genotype on ICs and GFs. Preliminary data suggest an association between increased vitreous cytokine levels and 1. increased drusen load and 2. increased chronologic age. These data suggest that risk factors of age and drusen promote AMD via a pro-inflammatory mechanism.
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