Ocular surface complications result from dysregulation of the OGF-OGFr signaling pathway in female diabetic rats.
Ocular surface complications result from dysregulation of the OGF-OGFr signaling pathway in female diabetic rats.
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DOI：
10.3892/etm.2021.10119
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发表时间：
2021-07
影响因子：
2.7
通讯作者：
Mclaughlin PJ
中科院分区：
文献类型：
--
作者：
Purushothaman I;Zagon IS;Sassani JW;Mclaughlin PJ
美国大约有 450 万女性患有与糖尿病相关的眼部并发症。这些并发症的时间进程和严重程度，以及它们与阿片生长因子 (OGF)-OGF 受体 (OGFr) 信号通路失调的关系尚不清楚。本研究调查了糖尿病雌性大鼠眼表并发症的发生和严重程度以及与 OGF-OGFr 信号通路失调的关系。成年雌性 Sprague-Dawley 大鼠被注射链脲佐菌素以建立 1 型糖尿病 (T1D) 模型，其中一部分接受胰岛素 (T1D-INS)。评估血糖、体重、泪液产生和角膜敏感性，以及 OGF 和 OGFr 的血清和组织表达水平。还评估了角膜上皮伤口愈合。在第二项研究中，雌性 T1D 大鼠接受局部纳曲酮 (NTX) 治疗，以确定 NTX 阻断 OGF-OGFr 信号通路是否会改变角膜表面并发症的发展。与对照组和 T1D-INS 大鼠相比，雌性 T1D 大鼠的血糖水平升高，体重减轻。在两个糖尿病组中，泪液产生在 2 周内减少，角膜敏感性在 5 周内下降 2.5 倍，而仅在 T1D 大鼠中角膜上皮伤口愈合延迟。糖尿病患者的血清和组织中 OGF 和 OGFr 水平升高。每日两次 NTX 治疗可逆转糖尿病雌性大鼠的大多数眼表并发症。目前的数据证明了雌性 T1D 大鼠的一项开创性发现，其中糖尿病相关眼表并发症的发生和严重程度与 OGF-OGFr 调节途径的失调有关。用阿片受体拮抗剂 NTX 阻断 OGF-OGFr 通路可以防止这些缺陷的发生和/或减轻这些缺陷的程度。目前的数据支持对糖尿病人类受试者的这种治疗方法进行转化研究的需要。
Approximately 4.5 million women in the United States exhibit diabetes-associated ocular complications. The time course and magnitude of these complications, and their association with the dysregulation of the opioid growth factor (OGF)-OGF receptor (OGFr) signaling pathway are unknown. The present study investigated the onset and magnitude of ocular surface complications and the association with a dysregulated OGF-OGFr signaling pathway in diabetic female rats. Adult female Sprague-Dawley rats were injected with streptozotocin in order to establish a model of type 1 diabetes (T1D), and a subset received insulin (T1D-INS). Blood glucose, body weight, tear production and corneal sensitivity, as well as serum and tissue expression levels of OGF and OGFr, were assessed. Corneal epithelial wound healing was also evaluated. In a second study, female T1D rats were treated with topical naltrexone (NTX) to determine whether blockade of the OGF-OGFr signaling pathway by NTX altered development of corneal surface complications. Female T1D rats had elevated glucose levels and reduced body weight compared with control and T1D-INS rats. In both diabetic groups, tear production was decreased within 2 weeks and corneal sensitivity was decreased 2.5-fold within 5 weeks, while corneal epithelial wound healing was delayed only in T1D rats. Serum and tissue levels of OGF and OGFr were elevated in diabetes. Twice daily NTX treatment reversed most ocular surface complications in the diabetic female rats. The present data demonstrated a seminal discovery in female T1D rats, in which the onset and magnitude of diabetes-associated ocular surface complications were associated with dysregulation of the OGF-OGFr regulatory pathway. Blockade of the OGF-OGFr pathway with the opioid receptor antagonist NTX prevented the onset and/or decreased the magnitude of these deficits. The current data support the need for translational research on this therapeutic approach for diabetic human subjects.
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影响因子：
2
作者：
NEGRI, M;FALLUCCA, F;PACHI, A
通讯作者：
PACHI, A
影响因子：
2.8
作者：
Zagon, IS;Sassani, JW;McLaughlin, PJ
通讯作者：
McLaughlin, PJ
影响因子：
5.1
作者：
Cho, N. H.;Shaw, J. E.;Malanda, B.
通讯作者：
Malanda, B.
影响因子：
4.1
作者：
Gagliano, Caterina;Caruso, Salvatore;Avitabile, Teresio
通讯作者：
Avitabile, Teresio
影响因子：
--
作者：
Zagon, Ian S.;Klocek, Matthew S.;Sassani, Joseph W.;McLaughlin, Patricia J.
通讯作者：
McLaughlin, Patricia J.