Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.
Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA.
Int J Mol Sci. 2023 Jun 29;24(13):10869. doi: 10.3390/ijms241310869.
The purpose of this study was to investigate the reason that diabetic retinopathy (DR) is delayed from the onset of diabetes (DM) in diabetic mice. To this end, we tested the hypothesis that the deleterious effects of DM are initially tolerated because endogenous antioxidative defense is elevated and thereby confers resistance to oxidative stress-induced death. We found that this was indeed the case in both type 1 DM (T1D) and type 2 DM (T2D) mouse models. The retinal expression of antioxidant defense genes was increased soon after the onset of DM. In addition, ischemia/oxidative stress caused less death in the retinal vasculature of DM versus non-DM mice. Further investigation with T1D mice revealed that protection was transient; it waned as the duration of DM was prolonged. Finally, a loss of protection was associated with the manifestation of both neural and vascular abnormalities that are diagnostic of DR in mice. These observations demonstrate that DM can transiently activate protection from oxidative stress, which is a plausible explanation for the delay in the development of DR from the onset of DM.
本研究旨在探讨糖尿病性视网膜病变（DR）从糖尿病（DM）发病开始延迟的原因。为此，我们检验了一个假设，即 DM 的有害影响最初是可以耐受的，因为内源性抗氧化防御增强，从而对氧化应激诱导的死亡产生抵抗。我们发现，在 1 型糖尿病（T1D）和 2 型糖尿病（T2D）小鼠模型中确实如此。DM 发病后不久，抗氧化防御基因在视网膜中的表达增加。此外，与非 DM 小鼠相比，DM 小鼠的视网膜血管中的缺血/氧化应激引起的死亡较少。对 T1D 小鼠的进一步研究表明，这种保护是短暂的；随着 DM 持续时间的延长，其保护作用减弱。最后，保护作用的丧失与神经和血管异常的表现有关，这些异常是 DM 小鼠 DR 的诊断特征。这些观察结果表明，DM 可以短暂激活对氧化应激的保护，这可以解释 DR 从 DM 发病开始的延迟发展。
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