Related Experiment Video
Updated: Aug 21, 2026
Ex Vivo OCT-Based Multimodal Imaging of Human Donor Eyes for Research into Age-Related Macular Degeneration
Published on: May 26, 2023
Receptor for advanced glycation end products and age-related macular degeneration
Kimberly A Howes1, Yang Liu, Joshua L Dunaief
1Moran Eye Center, University of Utah Health Science Center, Salt Lake City, UT 84112, USA. kim.howes@hsc.utah.edu
Purpose:
Advanced glycation end products (AGE) exacerbate disease progression through two general mechanisms: modifying molecules and forming nondegradable aggregates, thus impairing normal cellular/tissue functions, and altering cellular function directly through receptor-mediated activation. In the present study receptor for AGE (RAGE)-mediated cellular activation was evaluated in the etiology of human retinal aging and disease.
Methods:
The maculas of human donor retinas from normal eyes and eyes with early age-related macular degeneration (AMD) and advanced AMD with geographic atrophy (GA) were assayed for AGE and RAGE by immunocytochemistry. Cultured ARPE-19 cells were challenged with known ligands for RAGE, AGE, and S100B, to test for activation capacity. Immunocytochemistry, real-time RT-PCR, immunoblot analysis, and the TUNEL assay were used to determine the consequences of RPE cellular activation.
Results:
Little to no immunolabeling for AGE or RAGE was found in photoreceptor and RPE cell layers in normal retinas. However, when small drusen were present, AGE and RAGE were identified in the RPE or both the RPE and photoreceptors. In early AMD and GA, the RPE and remnant photoreceptor cells showed intense AGE and RAGE immunolabeling. Both AGE and S100B activated cultured RPE cells, as revealed by upregulated expression of RAGE, NFkappaB nuclear translocation, and apoptotic cell death.
Conclusions:
Immunolocalization of RAGE in RPE and photoreceptors coincided with AGE deposits and macular disease in aged, early AMD, and GA retinas. Further, AGE stimulated RAGE-mediated activation of cultured ARPE-19 cells in a dose-dependent fashion. AGE accumulation, as occurs with normal aging and in disease, may induce receptor-mediated activation of RPE/photoreceptor cells, contributing to disease progression in the aging human retinas.
Insights
Advanced glycation end products (AGE) and their receptor (RAGE) accumulate in aging retinas, contributing to age-related macular degeneration (AMD). AGEs activate RAGE in retinal cells, promoting disease progression.
Area of Science:
- Ophthalmology and vision science.
- Cellular biology and molecular mechanisms of aging.
Background:
- Advanced glycation end products (AGE) contribute to aging and disease by modifying cellular functions.
- Receptor for AGE (RAGE) mediates cellular responses to AGEs, impacting tissue homeostasis.
Purpose of the Study:
- To investigate the role of RAGE-mediated cellular activation in human retinal aging and age-related macular degeneration (AMD).
Main Methods:
- Immunocytochemistry was used to detect AGE and RAGE in human donor retinas with varying stages of AMD.
- Cultured retinal pigment epithelium (RPE) cells (ARPE-19) were stimulated with AGEs and S100B to assess RAGE activation.
- Real-time RT-PCR, immunoblot analysis, and TUNEL assays quantified cellular responses.
Main Results:
- AGE and RAGE were minimally present in normal retinas but increased significantly in retinas with drusen, early AMD, and geographic atrophy (GA).
- AGE and S100B activated cultured RPE cells, leading to increased RAGE expression, NF-kappaB translocation, and apoptosis.
- RAGE localization in RPE and photoreceptors correlated with AGE deposits and macular disease.
Conclusions:
- RAGE expression in retinal cells coincides with AGE accumulation and AMD progression.
- AGEs activate RAGE in a dose-dependent manner, inducing cellular dysfunction and apoptosis.
- AGE accumulation and subsequent RAGE activation may drive retinal aging and AMD pathogenesis.
