Prenatal alcohol exposure may cause cardiac development defects, however, the underlying mechanisms are not yet clear. In the present study we have investigated the roles of histone modification by curcumin on alcohol induced fetal cardiac abnormalities during the development. Q-PCR and Western blot results showed that alcohol exposure increased gene and active forms of caspase-3 and caspase-8, while decreased gene and protein of bcl-2. ChIP assay results showed that, alcohol exposure increased the acetylation of histone H3K9 near the promoter region of caspase-3 and caspase-8, and decreased the acetylation of histone H3K9 near the promoter region of bcl-2. TUNEL assay data revealed that alcohol exposure increased the apoptosis levels in the embryonic hearts. In vitro experiments demonstrated that curcumin treatment could reverse the up-regulation of active forms of caspase-3 and caspase-8, and down-regulation of bcl-2 induced by alcohol treatment. In addition, curcumin also corrected the high level of histone H3K9 acetylation induced by alcohol. Moreover, the high apoptosis level induced by alcohol was reversed after curcumin treatment in cardiac cells. These findings indicate that histone modification may play an important role in mediating alcohol induced fetal cardiac apoptosis, possibly through the up-regulation of H3K9 acetylation near the promoter regions of apoptotic genes. Curcumin treatment may correct alcohol-mediated fetal cardiac apoptosis, suggesting that curcumin may play a protective role against alcohol abuse caused cardiac damage during pregnancy.

Retinal neurovascular coupling reflects the precise coordination between neuronal activity, glial support, and vascular responses, mirroring key neurovascular mechanisms in the brain. This review emphasizes the cellular and molecular processes underlying retinal neurovascular coupling and positions the retina as a sensitive and accessible model for investigating neurovascular function in the brain. It highlights how parallel neurovascular degeneration in the brain and retina provides critical insights into the pathophysiology of neurodegenerative and vascular disorders. Advances in retinal imaging, including functional optical coherence tomography (fOCT), OCT angiography (OCTA), and functional electrophysiology, offer unprecedented opportunities to detect early neuronal and vascular dysfunction, establishing the retina as a non-invasive biomarker for early detection, disease monitoring, and therapeutic evaluation in Alzheimer’s, Parkinson’s and Huntington’s disease, and stroke. By integrating structural, functional, and mechanistic approaches, the review emphasizes the retina’s potential as a translational platform bridging basic science and clinical applications in neurovascular research.

Carbamathione (Carb), an NMDA glutamate receptor partial antagonist, has potent neuroprotective functions against hypoxia- or ischemia-induced neuronal injury in cell- or animal-based stroke models. We used PC-12 cell cultures as a cell-based model and bilateral carotid artery occlusion (BCAO) for stroke. Whole-cell patch clamp recording in the mouse retinal ganglion cells was performed. Key proteins involved in apoptosis, endoplasmic reticulum (ER) stress, and heat shock proteins were analyzed using immunoblotting. Carb is effective in protecting PC12 cells against glutamate- or hypoxia-induced cell injury. Electrophysiological results show that Carb attenuates NMDA-mediated glutamate currents in the retinal ganglion cells, which results in activation of the AKT signaling pathway and increased expression of pro-cell survival biomarkers, e.g., Hsp 27, P-AKT, and Bcl2 and decreased expression of pro-cell death markers, e.g., Beclin 1, Bax, and Cleaved caspase 3, and ER stress markers, e.g., CHOP, IRE1, XBP1, ATF 4, and eIF2α. Using the BCAO animal stroke model, we found that Carb reduced the brain infarct volume and decreased levels of ER stress markers, GRP 78, CHOP, and at the behavioral level, e.g., a decrease in asymmetric turns and an increase in locomotor activity. These findings for Carb provide promising and rational strategies for stroke therapy.

Amacrine cells assemble complex circuits in the inner retina, where they integrate, modulate, and relay spatial and temporal information to retinal ganglion cells. Nevertheless, their organization and functional diversity are still not fully understood. In this study, we identify a distinct group of amacrine cells that express the stem cell factor receptor—c-Kit. Using combined techniques of anti-CD117 (c-Kit) immunolabeling, confocal imaging, and computational algorithms, we characterize the morphological features and spatial distribution of the c-Kit–expressing amacrine cells. Our results show that c-Kit-expressing amacrine cells are GABA-positive neurons with medium to wide dendritic fields that stratify within the specific strata in both ON and OFF sublaminae of the inner plexiform layer (IPL). The density recovery profile of c-Kit cells reveals regulated intercellular spacing, supporting the notion that they represent a single amacrine subtype with significant variation in their dendritic structures. Notably, a subset of these cells also bears ascending processes projecting into the outer plexiform layer (OPL). This distinct anatomical feature raises the possibility that c-Kit-expressing amacrine cells contribute to a long-range circuit across retinal layers and participate in a novel feedback pathway. Further analysis demonstrates that c-Kit–expressing amacrine cells are distinct from AII, starburst, nGnG, vGluT3-positive, VIP-positive, and dopaminergic amacrine cells. Our findings provide a new insight into the cellular diversity of amacrine cells and suggest a previously unrecognized functional role for c-Kit–expressing amacrine cells in the mammalian retina.