In retinitis pigmentosa (RP), one of many possible genetic mutations causes rod degeneration, followed by cone secondary death leading to blindness. Here, we provide the undercurrent knowledge on NGB distribution in retinal layers and the evidence about the connection between NGB level modulation and the functional outcome in terms of retinal neuroprotection to provide a novel therapeutic/preventive target for visual pathway degenerative disease. Indeed, the NGB capability to reversibly bind oxygen and its neuroprotective function against several types of insults including oxidative stress, ischemia, and neurodegenerative conditions have raised the interest in the possible role of the globin as oxygen supplier in the retina and as a target for retinal neurodegeneration. The discovering of the intracellular monomeric globin neuroglobin (NGB), found at high concentration in the retina, has opened new possibilities for the treatment of retinal disease. Increasing efforts have been made to identify and potentiate endogenous protective mechanisms or to abolish detrimental stress responses to preserve retinal structure and function. Due to the complexity of the tissue, and the diversity of retinal neurodegenerative diseases in terms of etiology and clinical presentation, so far, there are no cures and only a few early pathological markers have been identified. Retinal neurodegeneration affects an increasing number of people worldwide causing vision impairments and blindness, reducing quality of life, and generating a great economic challenge. These findings need to be investigated in human studies, particularly through a clinical trial. Moreover, phycocyanin was a major active compound of S. maxima could be a potential nutraceutical approach to intercept the patho-physiological processes leading to dry AMD and advancement to wet AMD. Phycocyanin exerted protective effects in the pre-and post-treatment system. maxima inhibited BL-induced retinal degeneration by restoring the thicknesses of whole retina, ONL (outer nuclear layer), INL (inner nuclear layer), and PL (photoreceptor layer) by BL exposure. maxima inhibited BL-induced inflammation via regulating the NF-κB pathway, inflammatory-related gene expression, and the apoptosis pathway in RPE cells. maxima decreased BL-induced RPE cell death by inhibiting reactive oxygen species (ROS) production. maxima on blue light-caused retinal damage and demonstrate its underlying mechanisms in human retinal pigment epithelial (ARPE-19) cells and Balb/c retinas. We aimed to investigate the protective effects of S. maxima and its underlying mechanisms on blue light (BL)-caused macular degeneration are unknown. maxima), a cyanobacterium, has inhibitory effects against oxidative stress. Thus, an antagonist that blocks GEF-H1 signaling effectively inhibits disease features in in vitro and in vivo disease models, demonstrating that GEF-H1 is an effective therapeutic target and establishing a new therapeutic approach.Īge-related macular degeneration (AMD) is a significant visual impairment in older people, and there is no treatment for dry AMD. Finally, the most potent inhibitor was successfully tested in an experimental retinal disease mouse model, in which it inhibited blood vessel leakage and ameliorated retinal inflammation when treatment was initiated after disease diagnosis. Successful inhibitors were then evaluated in models of TGFβ-induced fibrosis, LPS-stimulated endothelial cell-cell junction disruption, and cell migration. Candidate inhibitors were tested for their ability to block RhoA/GEF-H1 binding in vitro, and their potency and specificity in cell-based assays. Inhibitors were designed using a structural in silico approach or by isolating an inhibitory sequence from the autoregulatory C-terminal domain. Here, we have generated peptide inhibitors to block the function of GEF-H1. The Rho guanine nucleotide exchange factor (GEF) GEF-H1/ARHGEF-2 is induced in disease and stimulates inflammatory and fibrotic processes, cell migration, and metastasis. Inflammation and fibrosis are important components of diseases that contribute to the malfunction of epithelia and endothelia.
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