Excessive dietary salt promotes neuroinflammation to worsen retinopathy in mice with streptozotocin-induced diabetes

Abstract

ObjectiveDiabetic 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. MethodsEight-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. ResultsA 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. ConclusionThese 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.