Purpose:
Oxidative stress and inflammation are important factors associated with the pathogenesis of age related macular degeneration (AMD). Amyloid beta (Aβ) and glycosylation end products (AGE) are peptides found in drusen, the hallmark extracellular deposits of "dry" AMD. Stimulation studies with these peptides caused gene expression changes in RPE in vitro. Genes most affected were in the immune response group and associated with leukocyte extravasation signalling and complement cascade pathways (IL-1β, CFI, CXCR1, RSAD2, STAT3). We hypothesize that drusen deposits may cause increased expression of inflammation associated genes in the human eye.
Methods:
Post mortem human eyes were paraffin embedded and tissue sections subjected to immunocytochemistry. Antibodies against IL-1β, CFI, CXCR1, RSAD2 and STAT3 were used on donors of two age groups: < 57 (N=13) and > 70 years (N=13). Immunoreactivity and analysis were undertaken in a masked manner and scored semi-quantitatively using bright field microscopy (20-60X). Intensity of staining was compared with negative control sections and graded from 0 to 3, with 3 representing robust immunoreactivity. Data were scored in the retina (GCL, IPL, INL, OPL, ONL IS, OS), RPE, Bruch’s membrane (BM), choroid (Ch), and drusen sites. Data were analyzed by one tailed T test of unequal variance (p ≤ 0.05).
Results:
Comparisons of the intensity of immunoreactivity were made between age groups (Old vs. Young) and between eyes that displayed drusen compared to those eyes that did not display drusen (Drusen vs. No Drusen). The relative immunoreactivity of the drusen sites in eyes with drusen was also scored (Drusen sites). Table 1 summarizes the results of the study.
Conclusions:
Increased chronologic age and presence of drusen deposits correlate with increased expression of inflammatory factors in the eye. Intensity of immunoreactivity was greatest for eyes with drusen. Older eyes without drusen were similar in immunoreactivity grading as younger eyes without drusen. The significance of these results in relation to pathogenesis of AMD will be discussed.
Keywords: age-related macular degeneration • cytokines/chemokines • retinal pigment epithelium