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Mohammad Dahrouj, Zsolt Ablonczy, Craig E. Crosson; Natriuretic Peptides Protect the RPE From AGE-Induced Barrier Breakdown. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5659.
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Advanced glycation end-products (AGEs), which form during aging and are increased in diabetic patients, have been implicated in the dysregulation of the RPE. Natriuretic peptides (NPs) are expressed in the eye and their receptors are found in the RPE. We have recently shown that RPE function is regulated by apically-administered NPs. Therefore, we began to investigate the ability of natriuretic peptides to suppress AGE-induced RPE barrier failure.
Transepithelial resistance (TER) measurements were utilized to assess the barrier function of monolayer-cultured ARPE-19 and human fetal RPE cells cultured on transwell filters. The cells were treated apically with 1 ng/mL to 100 µg/mL glycated (AGEs model) or non-glycated albumin in the absence or presence of 1 pM to 100 nM of apical ANP and BNP. TER was monitored for up to 24 hours post drug-administration.
Glycated albumin induces a significant reduction in TER within two hours. This response was concentration-dependent (EC50 = 1.8µg/mL) with a maximal reduction in TER of 33% at 100 µg/mL within 2 hours. Administration of normal albumin (100µg/mL) alone did not significantly alter TER. One hour pretreatment with ANP blocked the reduction in TER induced by glycated albumin (10µg/mL). The IC50 for this ANP response was 1.3 nM. One hour pretreatment with BNP also blocked the reduction in TER induced by glycated albumin with an IC50 of 0.1 nM.
Our data demonstrate glycated albumin is effective in reducing RPE barrier function, and this response may contribute to the development of diabetic retinal edema. The ability of both ANP and BNP to block the AGE-induced effects provides evidence that these responses are mediated by NP receptors. These studies support the idea that NP receptor agonists are potential candidates for treating retinal complications in diabetic patients.
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