Diabetic retinopathy (DR) is a leading cause of vision loss among working-age adults and is characterized by progressive retinal microvascular dysfunction driven by hyperglycemia-induced inflammation and oxidative stress. Histone deacetylase 6 (HDAC6), a cytoplasmic deacetylase involved in multiple cellular processes, has been implicated in vascular pathology; however, its specific role in retinal endothelial cells remains unclear. In this study, we investigated whether endothelial-specific deletion of HDAC6 protects against diabetic retinal injury. Endothelial HDAC6 knockout mice were generated using VE-cadherin–Cre recombination and subjected to streptozotocin-induced diabetes. Retinal vascular integrity, inflammatory and oxidative stress responses, endothelial senescence, and visual function were assessed during the course of hyperglycemia. Diabetic control mice developed characteristic features of DR, including vascular dysfunction, heightened inflammatory and oxidative stress responses, increased endothelial senescence, and impaired visual function. In contrast, endothelial-specific HDAC6 deletion markedly attenuated these pathological changes, preserving retinal vascular integrity and visual performance while reducing oxidative stress and inflammation. These findings identify endothelial HDAC6 as a key contributor to diabetes-induced retinal vascular injury and suggest that targeting endothelial HDAC6 may represent a promising therapeutic strategy for preventing microvascular damage and vision loss in DR.

Isomalto/malto-polysaccharide (IMMP) is a digestion resistant starch that has shown to increase SCFA production in the gut microbiota of human and mice to promote intestinal health. Like other prebiotics, it escapes enzymatic digestion in the small intestine and reaches the colon intact where it can interact with host epithelial and immune cells. Recently it was shown that in vitro IMMP can bind TLR4 on human macrophages resulting in their activation. The purpose of the present study was to investigate putative immune activation effects of IMMP upon direct interaction with chicken macrophages. IMMP stimulation in vitro caused morphological changes in the macrophage cell line HD11 reflected as reduction in cell size and numbers of cytoplasmic projections. Using the extracellular TLR4 blocking agent LPS-RS, it was shown that IMMP stimulation of HD11 cells involved TLR4 signaling. In addition, it activated HD11 cells and monocyte derived macrophages, resulting in the production of nitric oxide and increased phagocytic activity of HD11 cells. In conclusion, our results demonstrate an in vitro effect of IMMP on chicken macrophages which suggests that this carbohydrate compound may have immunomodulatory potential, hence may be used in the future as an alternative strategy to strengthen immune responsiveness to control intestinal infections.