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PACAP 和 PARP 抑制剂的联合应用具有治疗糖尿病和高血压性视网膜病变模型的潜力。

A Promising Combination: PACAP and PARP Inhibitor Have Therapeutic Potential in Models of Diabetic and Hypertensive Retinopathies.

机构信息

Department of Experimental Zoology and Neurobiology, University of Pécs, 7624 Pécs, Hungary.

Department of Medical Biology, Medical School, University of Pécs, 7624 Pécs, Hungary.

出版信息

Cells. 2021 Dec 9;10(12):3470. doi: 10.3390/cells10123470.

DOI:10.3390/cells10123470
PMID:34943979
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8700737/
Abstract

Diabetes and hypertension are complex pathologies with increasing prevalence nowadays. Their interconnected pathways are frequently manifested in retinopathies. Severe retinal consequences and their tight connections as well as their possible treatments are particularly important to retinal research. In the present, work we induced diabetes with streptozotocin in spontaneously hypertensive rats and treated them either with PACAP or olaparib and alternatively with both agents. Morphological and immunohistochemical analyses were carried out to describe cell-specific changes during pathologies and after different treatments. Diabetes and hypertension caused massive structural and cellular changes especially when they were elicited together. Hypertension was crucial in the formation of ONL and OPL damage while diabetes caused significant differences in retinal thickness, OPL thickness and in the cell number of the GCL. In diabetes, double neuroprotective treatment ameliorated changes of calbindin-positive cells, rod bipolar cells and dopaminergic amacrine cells. Double treatment was curative in hypertensive diabetic rat retinas, especially in the case of rod bipolar and parvalbumin-positive cells compared to untreated or single-treated retinas. Our results highlighted the promising therapeutic benefits of olaparib and PACAP in these severe metabolic retinal disorders.

摘要

糖尿病和高血压是现今患病率日益增加的复杂病理。它们相互关联的途径经常表现在视网膜病变中。严重的视网膜后果及其紧密联系以及它们可能的治疗方法对视网膜研究尤为重要。在目前的工作中,我们用链脲佐菌素诱导自发性高血压大鼠患上糖尿病,并分别用 PACAP 或奥拉帕利,或者两种药物交替治疗。进行形态学和免疫组织化学分析,以描述病理过程中和不同治疗后的细胞特异性变化。糖尿病和高血压引起了大量的结构和细胞变化,特别是当它们一起引发时。高血压对 ONL 和 OPL 损伤的形成至关重要,而糖尿病导致视网膜厚度、OPL 厚度和 GCL 细胞数量出现显著差异。在糖尿病中,双重神经保护治疗改善了 calbindin 阳性细胞、视杆双极细胞和多巴胺能无长突细胞的变化。与未治疗或单一治疗的视网膜相比,双重治疗对高血压糖尿病大鼠的视网膜具有治疗效果,尤其是在视杆双极细胞和 parvalbumin 阳性细胞方面。我们的结果强调了奥拉帕利和 PACAP 在这些严重代谢性视网膜疾病中的有前途的治疗益处。

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本文引用的文献

1
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2
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3
Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension.
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Invest Ophthalmol Vis Sci. 2024 Sep 3;65(11):8. doi: 10.1167/iovs.65.11.8.
4
Localization of Calretinin, Parvalbumin, and S100 Protein in Retina: A Suitable Model for the Retina Aging.钙视网膜蛋白、小白蛋白和S100蛋白在视网膜中的定位:视网膜衰老的合适模型
Life (Basel). 2023 Oct 13;13(10):2050. doi: 10.3390/life13102050.
5
Three Major Causes of Metabolic Retinal Degenerations and Three Ways to Avoid Them.三大代谢性视网膜退行性疾病的病因及三种预防方法。
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6
Potential Neuroprotective Role of Calretinin-N18 and Calbindin-D28k in the Retina of Adult Zebrafish Exposed to Different Wavelength Lights.潜在神经保护作用的 calretinin-N18 和 calbindin-D28k 在视网膜的成年斑马鱼暴露在不同波长的光。
Int J Mol Sci. 2023 Jan 6;24(2):1087. doi: 10.3390/ijms24021087.
神经血管单元处的血管-神经元耦合与神经血管耦合:高血压的影响
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4
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5
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6
Intraocular pressure fluctuation and neurodegeneration in the diabetic rat retina.糖尿病大鼠视网膜内眼压波动与神经退行性变。
Br J Pharmacol. 2020 Jul;177(13):3046-3059. doi: 10.1111/bph.15033. Epub 2020 Apr 15.
7
Protective effect of PACAP-38 on retinal pigmented epithelium in an in vitro and in vivo model of diabetic retinopathy through EGFR-dependent mechanism.PACAP-38 通过 EGFR 依赖性机制对糖尿病视网膜病变的体外和体内模型中的视网膜色素上皮的保护作用。
Peptides. 2019 Sep;119:170108. doi: 10.1016/j.peptides.2019.170108. Epub 2019 Jun 24.
8
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Invest Ophthalmol Vis Sci. 2019 Apr 1;60(5):1478-1490. doi: 10.1167/iovs.18-25936.
9
Poly ADP ribosylation and extracellular vesicle activity in rod photoreceptor degeneration.聚 ADP 核糖基化和杆状光感受器变性中的细胞外囊泡活性。
Sci Rep. 2019 Mar 6;9(1):3758. doi: 10.1038/s41598-019-40215-3.
10
Combination therapy in the treatment of hypertension.高血压治疗中的联合疗法。
Drugs Context. 2018 Jun 6;7:212531. doi: 10.7573/dic.212531. eCollection 2018.