Sex Differences in Diabetic Ocular Surface Complications and Dysregulation of the OGF-OGFr Pathway.
Sex Differences in Diabetic Ocular Surface Complications and Dysregulation of the OGF-OGFr Pathway.
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DOI：
10.33696/diabetes.4.052
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
McLaughlin, Patricia J
中科院分区：
文献类型：
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作者：
Zagon, Ian S;Sassani, Joseph W;McLaughlin, Patricia J
糖尿病是一种慢性疾病，影响全球超过5亿人。它是一种终生性疾病，并发症几乎会攻击身体内的所有其他系统。虽然男性糖尿病患病率略有增加，但男性和女性的眼表并发症同样存在。本文综述了与生物途径失调相关的临床前研究，该生物途径似乎与糖尿病眼表并发症（包括干眼、角膜上皮愈合延迟和角膜敏感性降低）有因果关系。大多数基础科学和临床研究都集中在动物模型中的雄性，以避免与激素循环相关的混杂因素。然而，美国18-44岁的所有女性中约有10.2%被诊断为糖尿病，另有近4%的女性患有未确诊的疾病，因此，谨慎的做法是检查女性中这些失调的发病情况，并注意眼表并发症发病时间或严重程度的任何性别相关差异。几项严格控制的研究数据表明，患有1型糖尿病的雌性大鼠比雄性大鼠更早发生眼表并发症。在某种程度上，这一发现可能是由于雌性动物在诱导高血糖症后2周内发生的抑制肽阿片样生长因子（OGF）增加，而雄性大鼠在4周时发生的OGF水平变化。注意到雌激素水平在诱导高血糖症的数周内下降，并且可以作为疾病活动和/或其并发症发作的另一个标志物。最后，胰岛素似乎不能防止糖尿病雌性大鼠OGF水平或雌激素分泌的早期变化，这为男性和女性之间糖尿病疾病特征的区别奠定了基础。这些数据鼓励对男女进行进一步研究，以全面了解与糖尿病并发症相关的潜在病理学。
Diabetes is a chronic disorder that affects more than 500 million individuals worldwide. It is a life-long disease with complications that attack nearly all other systems within the body. Although there is a slight increase in the prevalence of diabetes in males, ocular surface complications are equally present in males and females. This review provides a discussion on preclinical studies related to the dysregulation of a biological pathway that appears to be causally related to diabetic ocular surface complications including dry eye, delayed corneal epithelial healing, and decreased corneal sensitivity. Most basic science and clinical studies focus on male sex in animal models in order to avoid confounders related to hormonal cycling. However, with approximately 10.2% of all women in the US aged 18-44 being diagnosed with diabetes and nearly 4% additional women having undiagnosed disease, it is prudent to examine the onset of these dysregulations also in females and to note any sex-related differences in the timing of onset or severity of ocular surface complications. Data from several well-controlled investigations have documented that female rats with type 1 diabetes develop ocular surface complications before male rats. In part, this finding may be due to the increase in the inhibitory peptide Opioid Growth Factor (OGF) that occurs within 2 weeks of the induction of hyperglycemia in female animals in comparison to the changes in OGF levels in male rats which occur at 4 weeks. It was noted that estrogen levels drop within weeks of induction of hyperglycemia and could serve as another marker for the onset of disease activity and/or its complications. Finally, insulin does not appear to protect against early changes in OGF levels or estrogen secretion in diabetic female rats, setting the stage for a distinction in the disease profile of diabetes between males and females. These data encourage further studies on both sexes in order to establish a complete understanding of the underlying pathologies associated with complications associated with diabetes.