Homer signaling pathways as effective therapeutic targets for ischemic and traumatic brain injuries and retinal lesions

Ischemic and traumatic insults to the central nervous system account for most serious acute and fatal brain injuries and are usually characterized by primary and secondary damage.Secondary damage presents the greatest challenge for medical staff;however,there are currently few effective therapeutic targets for secondary damage.Homer proteins are postsynaptic scaffolding proteins that have been implicated in ischemic and traumatic insults to the central nervous system.Homer signaling can exert either positive or negative effects during such insults,depending on the specific subtype of Homer protein.Homer 1b/c couples with other proteins to form postsynaptic densities,which form the basis of synaptic transmission,while Homer 1a expression can be induced by harmful external factors.Homer 1c is used as a unique biomarker to reveal alterations in synaptic connectivity before and during the early stages of apoptosis in retinal ganglion cells,mediated or affected by extracellular or intracellular signaling or cytoskeletal processes.This review summarizes the structural features,related signaling pathways,and diverse roles of Homer proteins in physiological and pathological processes.Upregulating Homer 1a or downregulating Homer 1b/c may play a neuroprotective role in secondary brain injuries.Homer also plays an important role in the formation of photoreceptor synapses.These findings confirm the neuroprotective effects of Homer,and support the future design of therapeutic drug targets or gene therapies for ischemic and traumatic brain injuries and retinal disorders based on Homer proteins.

Necroptosis plays a crucial role in the exacerbation of retinal injury after blunt ocular trauma

Retinal injury after blunt ocular trauma may directly affect prognosis and lead to vision loss.To investigate the pathological changes and molecular mechanisms involved in retinal injury after blunt ocular trauma,we established a weight drop injury model of blunt ocular trauma in male Beagle dogs.Hematoxylin-eosin staining,immunofluorescence staining,western blotting,and TUNEL assays were performed to investigate retinal injury within 14 days after blunt ocular trauma.Compared with the control group,the thicknesses of the inner and outer nuclear layers,as well as the number of retinal ganglion cells,gradually decreased within 14 days after injury.The number of bipolar cells in the inner nuclear layer began to decrease 1 day after injury,while the numbers of cholinergic and amacrine cells in the inner nuclear layer did not decrease until 7 days after injury.Moreover,retinal cell necroptosis increased with time after injury;it progressed from the ganglion cell layer to the outer nuclear layer.Visual electrophysiological findings indicated that visual impairment began on the first day after injury and worsened over time.Additionally,blunt ocular trauma induced nerve regeneration and Müller glial hyperplasia;it also resulted in the recruitment of microglia to the retina and polarization of those microglia to the M1 phenotype.These findings suggest that necroptosis plays an important role in exacerbating retinal injury after blunt ocular trauma via gliosis and neuroinflammation.Such a role has important implications for the development of therapeutic strategies.