IGF-1, mTOR Signaling, and Neurodegeneration Across Eye and Brain

This audio article is from VisualFieldTest.com.Read the full article here: https://visualfieldtest.com/en/igf-1-mtor-signaling-and-neurodegeneration-across-eye-and-brainTest your visual field online: https://visualfieldtest.comSupport the show so new episodes keep coming: https://www.buzzsprout.com/2563091/supportExcerpt:Introduction Glaucoma is now recognized not just as an eye pressure problem but as a neurodegenerative disease of the optic nerve. Retinal ganglion cells (RGCs) – the neurons that send visual signals from eye to brain – degenerate in glaucoma, much like neurons die in Alzheimer’s or Parkinson’s disease () (). Researchers are uncovering how general health factors – hormones, metabolism, even stress levels – affect RGC survival. In particular, the IGF-1 (Insulin-like Growth Factor 1) and mTOR (mammalian Target Of Rapamycin) pathways, which normally promote cell growth and protein building, play important roles in eye health. Disturbances to these pathways (for example, from insulin resistance or poor nutrition) can converge on the axonal transport systems in neurons and stress RGCs. By comparing glaucoma to brain disorders, we can learn how these signals protect or harm nerves. This article reviews the evidence linking IGF-1, mTOR signaling, metabolic health, and nervous system balance to glaucoma risk, and highlights what blood or other tests might tell you about your eye–brain health.IGF-1, Insulin, and the mTOR Pathway in Nerve Cells IGF-1 is a small protein hormone closely related to insulin. It is made in the liver (and in some tissues) under the influence of growth hormone. In the body, IGF-1 encourages growth and survival of many cell types (). In the nervous system, IGF-1 is especially important for neuron growth and neuroprotection. For example, in lab studies IGF-1 significantly protected retinal ganglion cells (RGCs) from dying under stress () (). When cultured RGCs were starved of oxygen (hypoxia), adding IGF-1 cut cell death by activating survival signaling pathways (the Akt/PI3K and Erk/MAPK routes) (). In other studies, boosting IGF-1 levels in injured optic nerves helped regenerate RGC axons () (). In short, IGF-1 acts like a neurotrophic (nerve-growing) factor that helps keep nerve cells alive and even regrow.The mTOR pathway is a central regulator of cell metabolism and growth. mTOR is a protein kinase (a “switch” enzyme) that senses nutrients, hormones, and energy. When nutrients and signals like insulin/IGF-1 are plentiful, mTOR becomes active (in two complexes, mTORC1 and mTORC2) and tells cells to grow and build protein () (). Conversely, when nutrients are low, mTOR activity falls and the cell ramps up recycling (autophagy) to conserve resources. In neurons, mTOR helps maintain dendrites and synapses. For example, one study found that mTORC1 (through its target S6 kinase, S6K) and mTORC2 (via a subunit SIN1) controlled the branching and length of RGC dendrites (). This means normal insulin/IGF-1 signaling through mTOR supports the complex dendritic trees of RGCs. In a powerful demonstration of this link, researchers showed that applying insulin directly to the eye in a mouse model of glaucoma stimulated RGC dendrite and synapse regeneration (). This treatment depended on the mTOR-S6K pathway: blocking S6K or its mTORC link (SIN1) prevented the regenerative effect (). In those experiments insulin rescued light responses and connectivity of RGCs, and improved the animals’ vision-like reflexes (). In sum, healthy IGF-1/insulin signaling through the mTOR pathway is crucial for RGC survival and function () (). Because the IGF/insulin and mTOR pathways are so intertwined, fitness and nutrition strSupport the show