Tau is an axon-enriched protein that binds to and stabilizes microtubules, hence plays a crucial role in neuronal function. In Alzheimer's disease (AD), pathological tau accumulation correlates with cognitive decline. Substantial visual deficits are found individuals affected by AD including preferential loss of retinal ganglion cells (RGCs), the neurons convey information from retina brain. At present, however, mechanisms underlie vision changes these patients poorly understood. Here, we...

Reduced blood flow and impaired neurovascular coupling are recognized features of glaucoma, the leading cause irreversible blindness worldwide, but mechanisms underlying these defects unknown. Retinal pericytes regulate microcirculatory coordinate through interpericyte tunneling nanotubes (IP-TNTs). Using two-photon microscope live imaging mouse retina, we found reduced capillary diameter at pericyte locations in eyes with high intraocular pressure, most important risk factor to develop...

The use of rodent models glaucoma has been essential to understand the molecular mechanisms that underlie pathophysiology this multifactorial neurodegenerative disease. With advent numerous transgenic mouse lines, there is increasing interest in inducible murine ocular hypertension. Here, we present an occlusion model based on injection magnetic microbeads into anterior chamber eye using a modified microneedle with facetted bevel. are attracted iridocorneal angle handheld magnet block...

Abstract Background The maintenance of complex dendritic arbors and synaptic transmission are processes that require a substantial amount energy. Bioenergetic decline is prominent feature chronic neurodegenerative diseases, yet the signaling mechanisms link energy stress with neuronal dysfunction poorly understood. Recent work has implicated deficits in glaucoma, retinal ganglion cell (RGC) pathology synapse disassembly key features ocular hypertension damage. Results We show adenosine...

Glaucoma is a leading cause of blindness. Although ocular hypertension the most important risk factor, several concomitant factors such as elevation glutamate and decrease in gamma-aminobutyric acid (GABA) levels, disorganized NO metabolism, oxidative damage could significantly contribute to neurodegeneration. The aim this report was analyze effect melatonin on retinal clearance, GABA concentrations, synthesis, redox status, well functional histological alterations provoked by chronic...

Deficits in mitochondrial transport are a common feature of neurodegenerative diseases. We investigated whether loss components the machinery impinge directly on metabolic stress, neuronal death, and circuit dysfunction. Using multiphoton microscope live imaging, we showed that ocular hypertension, major risk factor glaucoma, disrupts mitochondria anterograde axonal leading to energy decline vulnerable neurons. Gene- protein-expression analysis revealed adaptor disrupted schizophrenia 1...

Dendrite pathology and synaptic loss result in neural circuit dysfunction, a common feature of neurodegenerative diseases. There is lack strategies that target dendritic regeneration to promote neurorecovery. We show daily human recombinant insulin eye drops stimulate retinal ganglion cell (RGC) dendrite synapse during ocular hypertension, risk factor develop glaucoma. demonstrate the ribosomal protein p70S6 kinase (S6K) essential for insulin-dependent regrowth. Furthermore, S6K...

Glaucoma is a leading cause of blindness worldwide, characterized by retinal ganglion cell degeneration and damage to the optic nerve. We investigated non-image forming visual system in an experimental model glaucoma rats induced weekly injections chondroitin sulphate (CS) eye anterior chamber. Animals were unilaterally or bilaterally injected with CS vehicle for 6 10 weeks. In retinas from eyes CS, similar decrease melanopsin Thy-1 levels was observed. number melanopsin-containing cells...

The use of rodent models glaucoma has been essential to understand the molecular mechanisms that underlie pathophysiology this multifactorial neurodegenerative disease. With advent numerous transgenic mouse lines, there is increasing interest in inducible murine ocular hypertension. Here, we present an occlusion model based on injection magnetic microbeads into anterior chamber eye using a modified microneedle with facetted bevel. are attracted iridocorneal angle handheld magnet block...

To study the effect of intracameral injections chondroitin sulfate (CS) on intraocular pressure (IOP), retinal function, and histology in rats.Acute or chronic CS were performed unilaterally rat anterior chamber, whereas contralateral eye was injected with vehicle. IOP daily weekly assessed by a tonometer. Retinal function scotopic electroretinography (ERG) visual pathway flash evoked potentials (VEPs), optic nerve head structure examined histologic analysis.A single injection 8 mg (but not...

Abstract In rats, iron deficiency produces an alteration in myelin formation. However, there is limited information on the effects of this condition oligodendroglial cell (OLGc) proliferation and maturation. present study, we further analyzed hypomyelination associated with by studying dynamics oligodendrogenesis. Rats were fed control (40 mg Fe/kg) or iron‐deficient (4 diets from gestation day 5 until postnatal 3 (P3) 11 (P11). OLGc proliferation, migration differentiation investigated...

Glaucoma is a leading cause of acquired blindness which may involve an ischemic-like insult to retinal ganglion cells and optic nerve head. We investigated the effect weekly application brief ischemia pulses (ischemic conditioning) on rat damage induced by experimental glaucoma. was injections chondroitin sulfate (CS) in eye anterior chamber. Retinal increasing intraocular pressure 120 mmHg for 5 min; this maneuver started after 6 vehicle or CS repeated one eye, while contralateral submitted...

Diabetic retinopathy is a leading cause of blindness. Intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin, are involved in non-image-forming visual responses such as photoentrainment circadian rhythms and pupillary light reflex. Since several reports indicate that affected by diabetes, we investigated system an advanced stage experimental diabetes rats induced streptozotocin. After 15 wks induction, clear alterations function were observed...

Autophagy dysfunction has been associated with several neurodegenerative diseases including glaucoma, characterized by the degeneration of retinal ganglion cells (RGCs). However, mechanisms which autophagy promotes RGC damage remain unclear. Here, we hypothesized that perturbation pathway results in increased autophagic demand, thereby downregulating signaling through mammalian target rapamycin complex 1 (mTORC1), a negative regulator autophagy, contributing to RGCs. We identified an...

The ability to derive retinal ganglion cells (RGCs) from human pluripotent stem (hPSCs) has led numerous advances in the field of research, with great potential for use hPSC-derived RGCs studies development, vitro disease modeling, drug discovery, as well their cell replacement therapeutics. Of all these possibilities, a human-relevant platform modeling received greatest attention, due translational relevance immediacy which results may be obtained compared more complex applications like...

The immune landscape of the tumor microenvironment (TME) is a determining factor in cancer progression and response to therapy. Specifically, density location cells TME have important diagnostic prognostic values. Multiomic profiling has exponentially increased our understanding numerous cellular molecular networks regulating initiation progression. However, these techniques do not provide information about spatial organization or cell-cell interactions. Affordable, accessible, easy execute...

Understanding the mechanisms of neuronal cell death in glaucoma is important for devising new treatments. Excitatory amino acids, excessive Ca(2+) influx, and formation nitric oxide (NO) via NO synthase (NOS)-1 could be involved glaucomatous neuropathy. The purpose present study was to examine retinal nitridergic pathway activity rats exposed experimentally elevated intraocular pressure.Weekly injections HA were performed unilaterally rat anterior chamber, whereas contralateral eye injected...

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder characterised by restrictive patterns of behaviour and alterations in social interaction communication. Up to 80% children with ASD exhibit sleep-wake cycle disturbances, emphasising the pressing need for novel approaches treatment ASD-associated comorbidities. While sleep disturbances have been identified individuals, little has done assess contribution circadian system these findings. The objective this study...

Radial optic neurotomy (RON) has been proposed as a surgical treatment to alleviate the neurovascular compression and improve venous outflow in patients with central retinal vein occlusion. Glaucoma is characterized by specific visual field defects due loss of ganglion cells damage nerve head (ONH). One clinical hallmarks glaucomatous neuropathy excavation ONH. The aim this work was analyze effect RON an experimental model glaucoma rats induced intracameral injections chondroitin sulfate...

Background: Metabolic stress has been proposed to contribute neuronal damage in glaucoma, but the mechanism driving this response is not understood. The adenosine monophosphate-activated protein kinase (AMPK) a master regulator of energy homeostasis that becomes active at onset stress. AMPK potent inhibitor mammalian target rapamycin complex 1 (mTORC1), which we showed essential for maintenance retinal ganglion cell (RGC) dendrites, synapses, and survival. Here, tested hypothesis an early...

Increased vascular leakage and endothelial cell (EC) dysfunction are major features of neurodegenerative diseases. Here, we investigated the mechanisms leading to EC dysregulation asked whether altered mitochondrial dynamics in ECs impinge on barrier integrity neurodegeneration. We show that ocular hypertension, a risk factor develop glaucoma, induced fragmentation retinal capillary accompanied by increased oxidative stress ultrastructural defects. Analysis components revealed overactivation...

In Brief Background: Radial optic neurotomy (RON) has been proposed as a treatment for central retinal vein occlusion. However, it is still under debate whether RON would be an adequate or dangerous procedure, and persuasive animal studies are lacking. The aim of this study was to analyze the early histologic functional outcomes in normal rat eyes. Methods: performed by cutting into nerve edge at nasal hemisphere, while contralateral eye underwent sham procedure. function assessed scotopic...