Abstract
Purpose: :
80K–H (AGE–R2) was initially identified as a PKC substrate. The biological role of the 80K–H is unclear but has been linked to several important (but thus far, seemingly diverse) cell activities including 1) cellular activation induced by advanced glycation end (AGE) products in complex with AGE–R1 and AGE–R3, 2) intracellular signaling associated with the fibroblast growth factor III receptor, 3) GLUT4 vesicle membrane transport involved in the insulin signaling cascade, 4) protein folding by deglycosylation in the endoplasmic reticulum, and 5) Ca2+ regulated activity of a transient receptor potential (TRP) channel. In general 80K–H appears to play a role in cell activation pathways through receptors at the plasma membrane. Altered expression and mutations in 80K–H have been linked to diabetes, aging, and autosomal dominant polycystic liver disease. We previously found that enhanced immunolabeling of RAGE, a receptor for AGE products, is associated with histopathology in the aging eye. Since AGE product deposition is associated with aging tissues, including the retina and RPE–choroid axis, we examined this additional cell activating AGE receptor complex protein, 80K–H, for corresponding alterations in immunohistochemical staining patterns.
Methods: :
Cryostat sections from human donor eyes ranging from 23 to 91 years in age were incubated with AGE–R2 and RAGE antibodies and labeled with the Vector Laboratories streptavidin–biotin HRP kit.
Results: :
While AGE–R2 immunoreactivity was sparse in photoreceptor and RPE cell layers, immunolabeling was greatly enhanced in these cell layers in regions showing drusen formation and histopathology associated with geographic atrophy and CNV. Therefore, AGE–R2 immunolabeling was virtually identical to RAGE immunolabeling.
Conclusions: :
AGE–R2 immunoreactivity in the aging eye is consistent with ongoing AGE product accumulation, RAGE upregulation and cellular activation in aging retinas. Additional studies will address the possible role of AGE products and their receptors in the aging eye.
Keywords: aging • retinal pigment epithelium • pathobiology