High altitude associated non-arteritic ischemic optic neuropathy

Hypobaric hypoxia in extreme high altitude leads to optic disc edema, cotton wool spots, and retinal vascular changes [1-3]. High altitude associated non-arteritic anterior ischemic optic neuropathy (NAION) has been described [4-7]. In this study, we examined the clinical manifestations of 5 cases of high altitude-associated NAION

Increase ER Stress in Ischemic Optic Neuropathy: Implications in Diabetes and Effects of Insulin Treatment

Non-arteritic anterior ischemic optic neuropathy (NAION) is due to loss of oxygen to the anterior optic nerve, a watershed area (1-2) and leads to degeneration of retinal ganglion cell (RGC) body and axons as well as loss of optic nerve oligodendrocytes and demyelination (3-6). NAION in animals with diabetes mellitus (DM) leads to significant increase in retinal edema, VEGF levels, and greater loss of RGCs (7). Diabetes is also associated with increased risk of metabolic stress, which is particularly prominent in cells with high metabolic activity such as RGCs and oligodendrocytes and may contribute to the development of NAION and bilateral involvement. In this study, we investigated endoplasmic reticulum (ER) stress responses after experimental NAION

NGF Eye Administration Recovers the TrkB and Glutamate/GABA Marker Deficit in the Adult Visual Cortex Following Optic Nerve Crush

Eye-drop recombinant human nerve growth factor (ed-rhNGF) has proved to recover the retina and optic nerve damage in animal models, including the unilateral optic nerve crush (ONC), and to improve visual acuity in humans. These data, associated with evidence that ed-rhNGF stimulates the brain derived neurotrophic factor (BDNF) in retina and cortex, suggests that NGF might exert retino-fugal effects by affecting BDNF and its receptor TrkB. To address these questions, their expression and relationship with the GABAergic and glutamatergic transmission markers, GAD65 and GAD67, vesicular inhibitory amino acid transporter (VGAT), and vesicular glutamate transporters 1 and 2 (VGLUT-1 and VGLUT-2) were investigated in adult ONC rats contralateral and ipsilateral visual cortex (VCx). Ed-rhNGF recovers the ONC-induced alteration of GABAergic and glutamatergic markers in contralateral VCx, induces an upregulation of TrkB, which is positively correlated with BDNF precursor (proBDNF) decrease in both VCx sides, and strongly enhances TrkB+ cell soma and neuronal endings surrounded by GAD65 immuno-reactive afferents. These findings contribute to enlarging the knowledge on the mechanism of actions and cellular targets of exogenously administrated NGF, and suggest that ed-rhNGF might act by potentiating the activity-dependent TrkB expression in GAD+ cells in VCx following retina damage and/or ONC

Multivariate analysis and diagnostic value of OCT and OCT angiography measurements of optic atrophy

Optical coherence tomography (OCT) and angiography (OCTA) [1-6] are common tests to consider in the evaluation; of patients with vision loss. It is unclear which OCT and OCTA measurements are most useful and whether OCTA; adds substantially to OCT. We performed a cross-sectional study to answer these questions

Mitochondrial Dysfunction in Patients With Nonarteritic Anterior Ischemic Optic Neuropathy and Optic Disc Drusen

The anterior optic nerve is packed with mitochondria to generate energy to support action potential conduction. Mitochondrial dysfunction leads to vision loss in dominant optic atrophy (DOA) and Leber hereditary optic neuropathy, and has been implicated in sporadic optic neuropathies. In this study, we asked whether skin fibroblasts from patients with acquired optic neuropathies such as nonarteritic anterior ischemic optic neuropathy (NAION) and optic disc drusen (ODD) exhibit mitochondrial dysfunction compared with those from dominant optic atrophy (DOA) and healthy controls

The Stressed Optic Nerve at High Altitude and Treatment with Chemical Chaperon

High altitude-associated non-arteritic anterior ischemic optic neuropathy (NAION) [1-3] typically occurs in younger patients who have disc-at-risk and few other risk factors [4-9], raising the possibility that hypobaric hypoxia may be the tipping point of vision loss. In this study, we investigated the effects of systemic hypoxia on the retina and optic nerve and assessed the therapeutic potential of pre-treatment with chemical chaperon 4-phenylbutyric acid (4- PBA), which reduces endoplasmic reticulum (ER) stress

The Stressed Optic Nerve at High Altitude and Treatment with Chemical Chaperon

High altitude-associated non-arteritic anterior ischemic optic neuropathy (NAION) [1-3] typically occurs in younger patients who have disc-at-risk and few other risk factors [4-9], raising the possibility that hypobaric hypoxia may be the tipping point of vision loss. In this study, we investigated the effects of systemic hypoxia on the retina and optic nerve and assessed the therapeutic potential of pre-treatment with chemical chaperon 4-phenylbutyric acid (4- PBA), which reduces endoplasmic reticulum (ER) stress

Paracrine signaling of human mesenchymal stem cell modulates retinal microglia population number and phenotype in vitro

Cellular therapy with mesenchymal stem cells (MSC) is emerging as an effective option to treat optic neuropathies. In models of retinal degeneration, MSC injected in the vitreous body protects injured retinal ganglion cells and stimulate their regeneration, however the mechanism is still unknown. Considering the immunomodulating proprieties of MSC and the controversial role of microglial contribution on retinal regeneration, we developed an in vitro co-culture model to analyze the effect of MSC on retinal microglia population.Fil: Teixeira Pinheiro, Leandro C.. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa; BrasilFil: Toledo, Maria Fernanda. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Nascimento dos Santos, Gabriel. Universidade Federal do Rio de Janeiro; BrasilFil: Mendez Otero, Rosalia. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa; BrasilFil: Mesentier Louro, Louise A.. University of Stanford; Estados Unidos. Universidade Federal do Rio de Janeiro; BrasilFil: Santiago, Marcelo F.. Universidade Federal do Rio de Janeiro; Brasil. Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa; Brasi

The Stressed Optic Nerve at High Altitude and Treatment with Chemical Chaperon

High altitude-associated non-arteritic anterior ischemic optic neuropathy (NAION) [1-3] typically occurs in younger patients who have disc-at-risk and few other risk factors [4-9], raising the possibility that hypobaric hypoxia may be the tipping point of vision loss. In this study, we investigated the effects of systemic hypoxia on the retina and optic nerve and assessed the therapeutic potential of pre-treatment with chemical chaperon 4-phenylbutyric acid (4- PBA), which reduces endoplasmic reticulum (ER) stress