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N(epsilon)(carboxymethyl)lysin and the AGE receptor RAGE colocalize in age-related macular degeneration
1Third Medical Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany.
Purpose:
To investigate whether glycoxidation products and the receptor for advanced glycation end products (RAGE) are present and colocalize in subfoveal membranes of patients with age-related macular degeneration (ARMD).
Methods:
Surgically removed subfoveal fibrovascular membranes from 12 patients, 11 related to ARMD and 1 to an idiopathic membrane, were analyzed for the presence of the glycoxidation product N(epsilon)-(carboxymethyl)lysin (CML), one of the receptors for advanced glycation end products, RAGE, and the activation of NFkB, using immunohistochemistry.
Results:
CML-like immunoreactivity was found in all ARMD specimens examined adjacent or colocalized with RAGE, but not in the idiopathic membrane. RAGE immunoreactive material was found in CD68-positive cells and in the fibrous matrix. CD68-positive cells and surrounding areas stained for p50, the activated form of NFkB.
Conclusions:
These results indicate that glycoxidation products are present in subretinal membranes of patients with ARMD. The concomitant expression of RAGE in these membranes and the finding of activated NFkB is suggestive of an implication of glycoxidation product formation in the pathogenesis of the disease.
Insights
Glycoxidation products and the receptor for advanced glycation end products (RAGE) are present in age-related macular degeneration (ARMD) membranes. Their colocalization with activated NFkB suggests a role in ARMD pathogenesis.
Area of Science:
- Ophthalmology
- Cell Biology
- Biochemistry
Background:
- Age-related macular degeneration (ARMD) is a leading cause of vision loss.
- The role of advanced glycation end products (AGEs) and their receptor (RAGE) in ARMD pathogenesis is under investigation.
- Glycoxidation products are a type of AGE.
Purpose of the Study:
- To determine if glycoxidation products and RAGE are present in subfoveal membranes from ARMD patients.
- To investigate the colocalization of these molecules within the membranes.
- To explore the potential involvement of NFkB signaling.
Main Methods:
- Immunohistochemistry was used to analyze surgically removed subfoveal fibrovascular membranes.
- The study examined 11 membranes from ARMD patients and 1 idiopathic membrane.
- Specific markers analyzed included N(epsilon)-(carboxymethyl)lysin (CML), RAGE, and activated NFkB (p50).
Main Results:
- CML-like immunoreactivity and RAGE were found in all ARMD membranes, often colocalized.
- RAGE was detected in CD68-positive cells and the fibrous matrix.
- Activated NFkB (p50) was present in CD68-positive cells and surrounding areas.
Conclusions:
- Glycoxidation products are present in subretinal membranes associated with ARMD.
- The co-expression of RAGE and activated NFkB suggests their involvement in ARMD pathogenesis.
- These findings highlight a potential therapeutic target related to AGEs and RAGE signaling in ARMD.