精氨酸酶
糖尿病性视网膜病变
氧化应激
内分泌学
NADPH氧化酶
内科学
炎症
医学
血-视网膜屏障
外渗
一氧化氮合酶
一氧化氮
视网膜
糖尿病
化学
精氨酸
免疫学
眼科
生物化学
氨基酸
作者
Ammar A. Abdelrahman,Katharine L. Bunch,Porsche Sandow,Paul N-M Cheng,Ruth B. Caldwell,R. William Caldwell
出处
期刊:Cells
[MDPI AG]
日期:2022-09-16
卷期号:11 (18): 2890-2890
被引量:2
标识
DOI:10.3390/cells11182890
摘要
Diabetic retinopathy (DR) is a serious complication of diabetes that results from sustained hyperglycemia, hyperlipidemia, and oxidative stress. Under these conditions, inducible nitric oxide synthase (iNOS) expression is upregulated in the macrophages (MΦ) and microglia, resulting in increased production of reactive oxygen species (ROS) and inflammatory cytokines, which contribute to disease progression. Arginase 1 (Arg1) is a ureohydrolase that competes with iNOS for their common substrate, L-arginine. We hypothesized that the administration of a stable form of Arg1 would deplete L-arginine’s availability for iNOS, thus decreasing inflammation and oxidative stress in the retina. Using an obese Type 2 diabetic (T2DM) db/db mouse, this study characterized DR in this model and determined if systemic treatment with pegylated Arg1 (PEG-Arg1) altered the progression of DR. PEG-Arg1 treatment of db/db mice thrice weekly for two weeks improved visual function compared with untreated db/db controls. Retinal expression of inflammatory factors (iNOS, IL-1β, TNF-α, IL-6) was significantly increased in the untreated db/db mice compared with the lean littermate controls. The increased retinal inflammatory and oxidative stress markers in db/db mice were suppressed with PEG-Arg1 treatment. Additionally, PEG-Arg1 treatment restored the blood–retinal barrier (BRB) function, as evidenced by the decreased tissue albumin extravasation and an improved endothelial ZO-1 tight junction integrity compared with untreated db/db mice.
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