Bilateral neuroinflammatory processes in visual pathways induced by unilateral ocular hypertension in the rat
Identifieur interne : 001961 ( Ncbi/Curation ); précédent : 001960; suivant : 001962Bilateral neuroinflammatory processes in visual pathways induced by unilateral ocular hypertension in the rat
Auteurs : Anaïs Sapienza [France] ; Anne-Laure Raveu [France] ; Elodie Reboussin [France] ; Christophe Roubeix [France] ; Céline Boucher [France] ; Julie Dégardin [France] ; David Godefroy [France] ; William Rostène [France] ; Annabelle Reaux-Le Goazigo [France] ; Christophe Baudouin [France] ; Stéphane Melik Parsadaniantz [France]Source :
- Journal of Neuroinflammation [ 1742-2094 ] ; 2016.
Abstract
Glaucoma is one of the leading causes of irreversible blindness in the world. The major risk factor is elevated intraocular pressure (IOP) leading to progressive retinal ganglion cell (RGC) death from the optic nerve (ON) to visual pathways in the brain. Glaucoma has been reported to share mechanisms with neurodegenerative disorders. We therefore hypothesize that neuroinflammatory mechanisms in central visual pathways may contribute to the spread of glaucoma disease. The aim of the present study was to analyze the neuroinflammation processes that occur from the pathological retina to the superior colliculi (SCs) in a rat model of unilateral ocular hypertension induced by episcleral vein cauterization (EVC).
Six weeks after unilateral (right eye) EVC in male Long-Evans rats, we evaluated both the neurodegenerative process and the neuroinflammatory state in visual pathway tissues. RGCs immunolabeled (Brn3a+) in ipsilateral whole flat-mounted retina demonstrated peripheral RGC loss associated with tissue macrophage/microglia activation (CD68+). Gene expression analysis of hypertensive and normotensive retinas revealed a significant increase of pro-inflammatory genes such as CCL2, IL-1β, and Nox2 mRNA expression compared to naïve eyes. Importantly, we found an upregulation of pro-inflammatory markers such as IL-1β and TNFα and astrocyte and tissue macrophage/microglia activation in hypertensive and normotensive RGC projection sites in the SCs compared to a naïve SC. To understand how neuroinflammation in the hypertensive retina is sufficient to damage both right and left SCs and the normotensive retina, we used an inflammatory model consisting in an unilateral stereotaxic injection of TNFα (25 ng/μl) in the right SC of naïve rats. Two weeks after TNFα injection, using an optomotor test, we observed that rats had visual deficiency in both eyes. Furthermore, both SCs showed an upregulation of genes and proteins for astrocytes, microglia, and pro-inflammatory cytokines, notably IL-1β. In addition, both retinas exhibited a significant increase of inflammatory markers compared to a naïve retina.
All these data evidence the complex role played by the SCs in the propagation of neuroinflammatory events induced by unilateral ocular hypertension and provide a new insight into the spread of neurodegenerative diseases such as glaucoma.
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DOI: 10.1186/s12974-016-0509-7
PubMed: 26897546
PubMed Central: 4761202
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Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff3">CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR_7210, Institut de la 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type="city">Montigny-Le-Bretonneux</settlement></placeName></affiliation></author><author><name sortKey="Melik Parsadaniantz, Stephane" sort="Melik Parsadaniantz, Stephane" uniqKey="Melik Parsadaniantz S" first="Stéphane" last="Melik Parsadaniantz">Stéphane Melik Parsadaniantz</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 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University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff3">CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Raveu, Anne Laure" sort="Raveu, Anne Laure" uniqKey="Raveu A" first="Anne-Laure" last="Raveu">Anne-Laure Raveu</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff3">CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Reboussin, Elodie" sort="Reboussin, Elodie" uniqKey="Reboussin E" first="Elodie" last="Reboussin">Elodie Reboussin</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff3">CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Roubeix, Christophe" sort="Roubeix, Christophe" uniqKey="Roubeix C" first="Christophe" last="Roubeix">Christophe Roubeix</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff3">CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Boucher, Celine" sort="Boucher, Celine" uniqKey="Boucher C" first="Céline" last="Boucher">Céline Boucher</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff3">CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Degardin, Julie" sort="Degardin, Julie" uniqKey="Degardin J" first="Julie" last="Dégardin">Julie Dégardin</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff3">CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Godefroy, David" sort="Godefroy, David" uniqKey="Godefroy D" first="David" last="Godefroy">David Godefroy</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff3">CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Rostene, William" sort="Rostene, William" uniqKey="Rostene W" first="William" last="Rostène">William Rostène</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff3">CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Reaux Le Goazigo, Annabelle" sort="Reaux Le Goazigo, Annabelle" uniqKey="Reaux Le Goazigo A" first="Annabelle" last="Reaux-Le Goazigo">Annabelle Reaux-Le Goazigo</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff3">CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Baudouin, Christophe" sort="Baudouin, Christophe" uniqKey="Baudouin C" first="Christophe" last="Baudouin">Christophe Baudouin</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff3">CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff4">CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC, 28 rue de Charenton, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC, 28 rue de Charenton, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff5">Department Ophthalmology, Hopital Ambroise Pare, AP HP, F-92100 Boulogne, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department Ophthalmology, Hopital Ambroise Pare, AP HP, F-92100 Boulogne</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Boulogne</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff6">University Versailles St Quentin En Yvelines, F-78180 Montigny-Le-Bretonneux, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>University Versailles St Quentin En Yvelines, F-78180 Montigny-Le-Bretonneux</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Montigny-Le-Bretonneux</settlement></placeName></affiliation></author><author><name sortKey="Melik Parsadaniantz, Stephane" sort="Melik Parsadaniantz, Stephane" uniqKey="Melik Parsadaniantz S" first="Stéphane" last="Melik Parsadaniantz">Stéphane Melik Parsadaniantz</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Universités, UPMC University of Paris 06, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff2">INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U968, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff3">CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CNRS UMR_7210, Institut de la Vision, 17 rue Moreau, 75012 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">Journal of Neuroinflammation</title><idno type="eISSN">1742-2094</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Glaucoma is one of the leading causes of irreversible blindness in the world. The major risk factor is elevated intraocular pressure (IOP) leading to progressive retinal ganglion cell (RGC) death from the optic nerve (ON) to visual pathways in the brain. Glaucoma has been reported to share mechanisms with neurodegenerative disorders. We therefore hypothesize that neuroinflammatory mechanisms in central visual pathways may contribute to the spread of glaucoma disease. The aim of the present study was to analyze the neuroinflammation processes that occur from the pathological retina to the superior colliculi (SCs) in a rat model of unilateral ocular hypertension induced by episcleral vein cauterization (EVC).</p></sec><sec><title>Results</title><p>Six weeks after unilateral (right eye) EVC in male Long-Evans rats, we evaluated both the neurodegenerative process and the neuroinflammatory state in visual pathway tissues. RGCs immunolabeled (Brn3a<sup>+</sup>) in ipsilateral whole flat-mounted retina demonstrated peripheral RGC loss associated with tissue macrophage/microglia activation (CD68<sup>+</sup>). Gene expression analysis of hypertensive and normotensive retinas revealed a significant increase of pro-inflammatory genes such as CCL2, IL-1β, and Nox2 mRNA expression compared to naïve eyes. Importantly, we found an upregulation of pro-inflammatory markers such as IL-1β and TNFα and astrocyte and tissue macrophage/microglia activation in hypertensive and normotensive RGC projection sites in the SCs compared to a naïve SC. To understand how neuroinflammation in the hypertensive retina is sufficient to damage both right and left SCs and the normotensive retina, we used an inflammatory model consisting in an unilateral stereotaxic injection of TNFα (25 ng/μl) in the right SC of naïve rats. Two weeks after TNFα injection, using an optomotor test, we observed that rats had visual deficiency in both eyes. Furthermore, both SCs showed an upregulation of genes and proteins for astrocytes, microglia, and pro-inflammatory cytokines, notably IL-1β. In addition, both retinas exhibited a significant increase of inflammatory markers compared to a naïve retina.</p></sec><sec><title>Conclusions</title><p>All these data evidence the complex role played by the SCs in the propagation of neuroinflammatory events induced by unilateral ocular hypertension and provide a new insight into the spread of neurodegenerative diseases such as glaucoma.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Quigley, Ha" uniqKey="Quigley H">HA Quigley</name></author><author><name sortKey="Broman, At" uniqKey="Broman A">AT Broman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weinreb, Rn" uniqKey="Weinreb R">RN Weinreb</name></author><author><name sortKey="Friedman, Ds" uniqKey="Friedman D">DS Friedman</name></author><author><name sortKey="Fechtner, Rd" uniqKey="Fechtner R">RD Fechtner</name></author><author><name sortKey="Cioffi, Ga" uniqKey="Cioffi G">GA 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