Centre for Animal Biotechnology and Gene Therapy (CBATEG), Universitat Autònoma de Barcelona, Bellaterra, Spain.
Department of Animal Health and Anatomy, Faculty of Veterinary Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Invest Ophthalmol Vis Sci. 2023 Mar 1;64(3):22. doi: 10.1167/iovs.64.3.22.
Iron overload causes oxidative damage in the retina, and it has been involved in the pathogeny of diabetic retinopathy, which is one of the leading causes of blindness in the adult population worldwide. However, how systemic iron enters the retina during diabetes and the role of blood retinal barrier (BRB) in this process remains unclear.
The db/db mouse, a well-known model of type 2 diabetes, and a model of systemic iron overload induced by iron dextran intraperitoneal injection, were used. Perls staining and mass spectrophotometry were used to study iron content. Western blot and immunohistochemistry of iron handling proteins were performed to study systemic and retinal iron metabolism. BRB function was assessed by analyzing vascular leakage in fundus angiographies, whole retinas, and retinal sections and by studying the status of tight junctions using transmission electron microscopy and Western blot analysis.
Twenty-week-old db/db mice with systemic iron overload presented ferritin overexpression without iron increase in the retina and did not show any sign of BRB breakdown. These findings were also observed in iron dextran-injected mice. In those animals, after BRB breakdown induced by cryopexy, iron entered massively in the retina.
Our results suggested that BRB protects the retina from excessive iron entry in early stages of diabetic retinopathy. Furthermore, ferritin overexpression before iron increase may prepare the retina for a potential BRB breakdown and iron entry from the systemic circulation.
铁过载会导致视网膜氧化损伤，并且与糖尿病性视网膜病变的发病机制有关，后者是全球成年人致盲的主要原因之一。然而，在糖尿病期间，全身铁如何进入视网膜以及血视网膜屏障 (BRB) 在该过程中的作用尚不清楚。
使用 db/db 小鼠，这是一种众所周知的 2 型糖尿病模型，以及通过腹腔内注射右旋糖酐铁诱导的全身铁过载模型。使用 Perls 染色和质谱分析来研究铁含量。通过 Western blot 和铁处理蛋白的免疫组织化学研究来研究全身和视网膜铁代谢。通过眼底血管造影、全视网膜和视网膜切片分析血管渗漏以及通过透射电子显微镜和 Western blot 分析研究紧密连接状态来评估 BRB 功能。
20 周龄的伴有全身铁过载的 db/db 小鼠表现出铁蛋白过度表达而视网膜中铁含量没有增加，并且没有任何 BRB 破坏的迹象。在右旋糖酐铁注射的小鼠中也观察到了这些发现。在那些动物中，在冷冻消融诱导 BRB 破坏后，铁大量进入视网膜。
我们的结果表明，BRB 在糖尿病性视网膜病变的早期阶段保护视网膜免受过量铁的进入。此外，铁增加前的铁蛋白过度表达可能为潜在的 BRB 破坏和来自全身循环的铁进入做好准备。
