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Dendrite pathology and synaptic loss result in neural circuit dysfunction, a common feature of neurodegenerative diseases. There is a lack of strategies that target dendritic and synaptic regeneration to promote neurorecovery. We show that daily human recombinant insulin eye drops stimulate retinal ganglion cell (RGC) dendrite and synapse regeneration during ocular hypertension, a risk factor to develop glaucoma. We demonstrate that the ribosomal protein p70S6 kinase (S6K) is essential for insulin-dependent dendritic regrowth. Furthermore, S6K phosphorylation of the stress-activated protein kinase-interacting protein 1 (SIN1), a link between the mammalian target of rapamycin complexes 1 and 2 (mTORC1/2), is required for insulin-induced dendritic regeneration. Using two-photon microscopy live retinal imaging, we show that insulin rescues single-RGC light-evoked calcium (Ca) dynamics. We further demonstrate that insulin enhances neuronal survival and retina-brain connectivity leading to improved optomotor reflex-elicited behaviors. Our data support that insulin is a compelling pro-regenerative strategy with potential clinical implications for the treatment and management of glaucoma.
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http://dx.doi.org/10.1126/sciadv.adl5722 | DOI Listing |
Chin Med J (Engl)
December 2024
Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong 510530, China.
Background: Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited.
View Article and Find Full Text PDFBackground: Bipolar disorder (BD) is a psychiatric condition with significant health implications due to its comorbidities, premature mortality, and functional impairments. Despite extensive research on treatment and rehabilitation, gaps remain in diagnosis and monitoring. Therefore, there is a need for biomarkers to identify individuals at risk for disease progression or excacerbation.
View Article and Find Full Text PDFEur Neuropsychopharmacol
December 2024
Barcelona Clinic Schizophrenia Unit, Institute of Neurosciences, Hospital Clinic, Barcelona, Spain; Institut d'Investigacions Mèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic, Barcelona, Spain; Biomedical Research Networking Centre Consortium on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain. Electronic address:
Emerging evidence suggests that retinal structural alterations are present in schizophrenia spectrum disorders (SSD), potentially reflecting broader neurodevelopmental and neurodegenerative processes. This cross-sectional study investigates retinal thickness and its clinical correlations in a sample of early-course SSD patients compared to healthy controls (HCs). One hundred-two eyes from 26 SSD cases and 25 age- and sex-matched HCs were included.
View Article and Find Full Text PDFAlzheimers Res Ther
December 2024
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Background: Dementia poses a significant burden on healthcare systems. Early identification of individuals at risk for cognitive decline is crucial. The retina, an extension of the central nervous system, reflects neurodegenerative changes.
View Article and Find Full Text PDFCell Mol Neurobiol
December 2024
Laboratory of Veterinary Biochemistry, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju, 63243, South Korea.
Chronic exposure to prenatal stress can impair neurogenesis and lead to irreversible cognitive and neuropsychiatric abnormalities in offspring. The retina is part of the nervous system; however, the impacts of prenatal stress on retinal neurogenesis and visual function remain unclear. This study examined how elevated prenatal glucocorticoid levels differentially affect retinal development in the offspring of pregnant mice exposed to chronic unpredictable mild stress (CUMS).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!