Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States of America; Department of Ophthalmology, The First Hospital of Jilin University, Changchun 130021, China.
Department of Anesthesiology, University of Virginia, Charlottesville, VA, United States of America.
Biochim Biophys Acta Mol Basis Dis. 2022 Sep 1;1868(9):166426. doi: 10.1016/j.bbadis.2022.166426. Epub 2022 May 6.
Diabetic retinopathy (DR) includes vascular and neural tissue injury. Persistent low-grade inflammation may contribute to DR. Increased salt intake has been shown to promote autoimmunity in the brain. This study determined the role of salt intake in DR development.
Eight-week-old C57BL/6 J male mice received streptozotocin to induce diabetes. Diabetic or non-diabetic mice were fed a diet containing normal, low and high amounts of salt. The retinal function, structure and inflammatory response were determined 8 weeks after the establishment of diabetes. Interleukin (IL)-1β or a NLR family pyrin domain containing 3 (NLRP3) inhibitor was injected intravitreally and the retinal changes were evaluated.
A high salt diet worsened the functional and structural damage of retinal cells and increased IL-1β in the retina of diabetic mice. IL-1β injection impaired the function of photoreceptors and retinal structure in the diabetic mice. Blocking NLRP3 inhibited IL-1β increase in the mouse bone marrow macrophages cultured in high sodium medium. NLRP3 inhibition attenuated retinal injury of diabetic mice on high salt diet. A low-salt diet also triggered inflammation and cell damage in the retina of diabetic mice but at a lower grade than those induced by high salt diet. A low or high salt diet for 8 weeks did not induce inflammation or cell injury in the retina of mice without diabetes.
These results indicate that high salt intake has deleterious effects in DR development through NLRP3 inflammasome activation and the subsequent production of IL-1β. Limiting salt intake may not attenuate DR development.
糖尿病视网膜病变（DR）包括血管和神经组织损伤。持续的低度炎症可能导致 DR。研究表明，盐摄入增加会促进大脑中的自身免疫。本研究旨在确定盐摄入量在 DR 发展中的作用。
8 周龄 C57BL/6J 雄性小鼠接受链脲佐菌素诱导糖尿病。糖尿病或非糖尿病小鼠分别喂食正常、低盐和高盐饮食。糖尿病建立 8 周后，检测视网膜功能、结构和炎症反应。玻璃体腔内注射白细胞介素（IL）-1β或 NLR 家族包含 pyrin 结构域 3（NLRP3）抑制剂，评估视网膜变化。
高盐饮食加重了糖尿病小鼠视网膜细胞的功能和结构损伤，并增加了视网膜中的 IL-1β。IL-1β 注射损害了糖尿病小鼠感光细胞的功能和视网膜结构。在高钠培养基中培养的小鼠骨髓巨噬细胞中，NLRP3 抑制抑制了 IL-1β 的增加。NLRP3 抑制减轻了糖尿病小鼠高盐饮食引起的视网膜损伤。低盐饮食也会引发糖尿病小鼠视网膜的炎症和细胞损伤，但程度低于高盐饮食。8 周低盐或高盐饮食不会引起无糖尿病小鼠视网膜的炎症或细胞损伤。
这些结果表明，高盐摄入通过 NLRP3 炎性小体激活和随后产生的 IL-1β 对 DR 发展产生有害影响。限制盐摄入可能不会减轻 DR 的发展。
