scholarly journals Neuronal Death in the Contralateral Un-Injured Retina after Unilateral Axotomy: Role of Microglial Cells

2019 ◽  
Vol 20 (22) ◽  
pp. 5733 ◽  
Author(s):  
Fernando Lucas-Ruiz ◽  
Caridad Galindo-Romero ◽  
Kristy T. Rodríguez-Ramírez ◽  
Manuel Vidal-Sanz ◽  
Marta Agudo-Barriuso
Keyword(s):  
Optic Nerve ◽  
Caspase 3 ◽  
Systemic Treatment ◽  
Significant Loss ◽  
Microglial Cells ◽  
Retinal Ganglion ◽  
Anti Inflammatory ◽  
Contralateral Response ◽  
Microglial Response

For years it has been known that unilateral optic nerve lesions induce a bilateral response that causes an inflammatory and microglial response in the contralateral un-injured retinas. Whether this contralateral response involves retinal ganglion cell (RGC) loss is still unknown. We have analyzed the population of RGCs and the expression of several genes in both retinas of pigmented mice after a unilateral axotomy performed close to the optic nerve head (0.5 mm), or the furthest away that the optic nerve can be accessed intraorbitally in mice (2 mm). In both retinas, RGC-specific genes were down-regulated, whereas caspase 3 was up-regulated. In the contralateral retinas, there was a significant loss of 15% of RGCs that did not progress further and that occurred earlier when the axotomy was performed at 2 mm, that is, closer to the contralateral retina. Finally, the systemic treatment with minocycline, a tetracycline antibiotic that selectively inhibits microglial cells, or with meloxicam, a non-steroidal anti-inflammatory drug, rescued RGCs in the contralateral but not in the injured retina. In conclusion, a unilateral optic nerve axotomy triggers a bilateral response that kills RGCs in the un-injured retina, a death that is controlled by anti-inflammatory and anti-microglial treatments. Thus, contralateral retinas should not be used as controls.

scholarly journals DDIT3 (CHOP) contributes to retinal ganglion cell somal loss but not axonal degeneration in DBA/2J mice

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Olivia J. Marola ◽  
Stephanie B. Syc-Mazurek ◽  
Richard T. Libby
Keyword(s):  
Optic Nerve ◽  
Ocular Hypertension ◽  
Optic Nerve Head ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Axonal Degeneration ◽  
Axonal Injury ◽  
Retinal Ganglion ◽  
Age Related

Abstract Glaucoma is an age-related neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Chronic ocular hypertension, an important risk factor for glaucoma, leads to RGC axonal injury at the optic nerve head. This insult triggers molecularly distinct cascades governing RGC somal apoptosis and axonal degeneration. The molecular mechanisms activated by ocular hypertensive insult that drive both RGC somal apoptosis and axonal degeneration are incompletely understood. The cellular response to endoplasmic reticulum stress and induction of pro-apoptotic DNA damage inducible transcript 3 (DDIT3, also known as CHOP) have been implicated as drivers of neurodegeneration in many disease models, including glaucoma. RGCs express DDIT3 after glaucoma-relevant insults, and importantly, DDIT3 has been shown to contribute to both RGC somal apoptosis and axonal degeneration after acute induction of ocular hypertension. However, the role of DDIT3 in RGC somal and axonal degeneration has not been critically tested in a model of age-related chronic ocular hypertension. Here, we investigated the role of DDIT3 in glaucomatous RGC death using an age-related, naturally occurring ocular hypertensive mouse model of glaucoma, DBA/2J mice (D2). To accomplish this, a null allele of Ddit3 was backcrossed onto the D2 background. Homozygous Ddit3 deletion did not alter gross retinal or optic nerve head morphology, nor did it change the ocular hypertensive profile of D2 mice. In D2 mice, Ddit3 deletion conferred mild protection to RGC somas, but did not significantly prevent RGC axonal degeneration. Together, these data suggest that DDIT3 plays a minor role in perpetuating RGC somal apoptosis caused by chronic ocular hypertension-induced axonal injury, but does not significantly contribute to distal axonal degeneration.

scholarly journals The Role of the IL-20 Subfamily in Glaucoma

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Mary K. Wirtz ◽  
Kate E. Keller
Keyword(s):  
Optic Nerve ◽  
Primary Open Angle Glaucoma ◽  
Peripheral Vision ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Common Disease ◽  
Retinal Ganglion ◽  
Ocular Tissues ◽  
Large Pedigree

Glaucoma is a common disease that leads to loss of peripheral vision and, if left untreated, ultimately to blindness. While the exact cause(s) of glaucoma is still unknown, two leading risk factors are age and elevated intraocular pressure. Several studies suggest a possible link between glaucoma and inflammation in humans and animal models. In particular, our lab recently identified a T104M mutation in IL-20 receptor-B (IL-20RB) in primary open angle glaucoma patients from a large pedigree. Several of the interleukin- (IL-) 20 family of cytokines and receptors are expressed in ocular tissues including the trabecular meshwork, optic nerve head, and retinal ganglion cells. The DBA/2J mouse develops high intraocular pressures with age and has characteristic optic nerve defects that make it a useful glaucoma model. IL-24 expression is significantly upregulated in the retina of these mice, while IL-20RA expression in the optic nerve is downregulated following pressure-induced damage. The identification of a mutation in theIL-20RBgene in a glaucoma pedigree and changes in expression levels of IL-20 family members in the DBA/2J mouse suggest that disruption of normal IL-20 signaling in the eye may contribute to degenerative processes associated with glaucoma.

scholarly journals The Effect of Plasma Rich in Growth Factors on Microglial Migration, Macroglial Gliosis and Proliferation, and Neuronal Survival

2021 ◽  
Vol 12 ◽  
Author(s):  
Noelia Ruzafa ◽  
Xandra Pereiro ◽  
Alex Fonollosa ◽  
Javier Araiz ◽  
Arantxa Acera ◽  
...  
Keyword(s):  
Growth Factors ◽  
Ganglion Cells ◽  
Platelet Rich Plasma ◽  
Microglial Cells ◽  
Heat Inactivation ◽  
Retinal Ganglion ◽  
Organotypic Cultures ◽  
Microglial Migration ◽  
Retinal Pathologies

Plasma rich in growth factors (PRGF) is a subtype of platelet-rich plasma that has being employed in the clinic due to its capacity to accelerate tissue regeneration. Autologous PRGF has been used in ophthalmology to repair a range of retinal pathologies with some efficiency. In the present study, we have explored the role of PRGF and its effect on microglial motility, as well as its possible pro-inflammatory effects. Organotypic cultures from adult pig retinas were used to test the effect of the PRGF obtained from human as well as pig blood. Microglial migration, as well as gliosis, proliferation and the survival of retinal ganglion cells (RGCs) were analyzed by immunohistochemistry. The cytokines present in these PRGFs were analyzed by multiplex ELISA. In addition, we set out to determine if blocking some of the inflammatory components of PRGF alter its effect on microglial migration. In organotypic cultures, PRGF induces microglial migration to the outer nuclear layers as a sign of inflammation. This phenomenon could be due to the presence of several cytokines in PRGF that were quantified here, such as the major pro-inflammatory cytokines IL-1β, IL-6 and TNFα. Heterologous PRGF (human) and longer periods of cultured (3 days) induced more microglia migration than autologous porcine PRGF. Moreover, the migratory effect of microglia was partially mitigated by: 1) heat inactivation of the PRGF; 2) the presence of dexamethasone; or 3) anti-cytokine factors. Furthermore, PRGF seems not to affect gliosis, proliferation or RGC survival in organotypic cultures of adult porcine retinas. PRGF can trigger an inflammatory response as witnessed by the activation of microglial migration in the retina. This can be prevented by using autologous PRGF or if this is not possible due to autoimmune diseases, by mitigating its inflammatory effect. In addition, PRGF does not increase either the proliferation rate of microglial cells or the survival of neurons. We cannot discard the possible positive effect of microglial cells on retinal function. Further studies should be performed to warrant the use of PRGF on the nervous system.

scholarly journals Perinatal Hypoxia-Ischemia Reducesα7 Nicotinic Receptor Expression and Selectiveα7 Nicotinic Receptor Stimulation Suppresses Inflammation and Promotes Microglial Mox Phenotype

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Sansan Hua ◽  
C. Joakim Ek ◽  
Carina Mallard ◽  
Maria E. Johansson
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Nicotinic Receptor ◽  
Receptor Expression ◽  
Brain Inflammation ◽  
Microglial Cells ◽  
Pcr Analysis ◽  
Neonatal Brain ◽  
Hypoxia Ischemia ◽  
Anti Inflammatory

Inflammation plays a central role in neonatal brain injury. During brain inflammation the resident macrophages of the brain, the microglia cells, are rapidly activated. In the periphery,α7 nicotinic acetylcholine receptors (α7R) present on macrophages can regulate inflammation by suppressing cytokine release. In the current study we investigatedα7R expression in neonatal mice after hypoxia-ischemia (HI). We further examined possible anti-inflammatory role ofα7R stimulationin vitroand microglia polarization afterα7R agonist treatment. Real-time PCR analysis showed a 33% reduction inα7R expression 72 h after HI. Stimulation of primary microglial cells with LPS in combination with increasing doses of the selectiveα7R agonist AR-R 17779 significantly attenuated TNFαrelease and increasedα7R transcript in microglial cells. Gene expression of M1 markers CD86 and iNOS, as well as M2 marker CD206 was not influenced by LPS and/orα7R agonist treatment. Further, Mox markers heme oxygenase (Hmox1) and sulforedoxin-1 (Srx1) were significantly increased, suggesting a polarization towards the Mox phenotype afterα7R stimulation. Thus, our data suggest a role for theα7R also in the neonatal brain and support the anti-inflammatory role ofα7R in microglia, suggesting thatα7R stimulation could enhance the polarization towards a reparative Mox phenotype.

scholarly journals Role of neuritin in retinal ganglion cell death in adult mice following optic nerve injury

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Yuriko Azuchi ◽  
Kazuhiko Namekata ◽  
Tadayuki Shimada ◽  
Xiaoli Guo ◽  
Atsuko Kimura ◽  
...  
Keyword(s):  
Cell Death ◽  
Optic Nerve ◽  
Ganglion Cell ◽  
Nerve Injury ◽  
Retinal Ganglion ◽  
Optic Nerve Injury ◽  
Adult Mice ◽  
Retinal Ganglion Cell Death ◽  
Ganglion Cell Death

scholarly journals Apoptotic Retinal Ganglion Cell Death After Optic Nerve Transection or Crush in Mice: Delayed RGC Loss With BDNF or a Caspase 3 Inhibitor

2016 ◽  
Vol 57 (1) ◽  
pp. 81 ◽  
Author(s):  
Maria C. Sánchez-Migallón ◽  
Francisco J. Valiente-Soriano ◽  
Francisco M. Nadal-Nicolás ◽  
Manuel Vidal-Sanz ◽  
Marta Agudo-Barriuso
Keyword(s):  
Cell Death ◽  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Caspase 3 ◽  
Retinal Ganglion ◽  
Nerve Transection ◽  
Retinal Ganglion Cell Death ◽  
Optic Nerve Transection ◽  
Ganglion Cell Death

scholarly journals Microglial Response to Aspergillus flavus and Candida albicans: Implications in Endophthalmitis

2020 ◽  
Vol 6 (3) ◽  
pp. 162
Author(s):  
Jaishree Gandhi ◽  
Poonam Naik ◽  
Inderjeet Kaur ◽  
Ashok Kumar ◽  
Joveeta Joseph
Keyword(s):  
Candida Albicans ◽  
Aspergillus Flavus ◽  
Fungal Pathogens ◽  
Microglial Cells ◽  
Time Intervals ◽  
Common Etiology ◽  
Infected Cells ◽  
Microglial Response ◽  
Metalloproteinase 9

Aspergillus flavus is the most common etiology of fungal endophthalmitis in India, while Candida albicans is the causative agent in the West. In this study, we determined the role of microglial cells in evoking an inflammatory response following an infection with A. flavus and C. albicans strains isolated from patients with endophthalmitis. Microglia (CHME-3) cells were infected with A. flavus and C. albicans and the expression of Toll-Like Receptors (TLRs), cytokines and Matrix metalloproteinases (MMPs) were assessed at various time intervals. A. flavus infected cells induced higher expressions of TLR-1, -2, -5, -6, -7 and -9 and cytokines such as IL-1α, IL-6, IL-8, IL-10 and IL-17. In contrast, C. albicans infected microglia induced only TLR-2 along with the downregulation of IL-10 and IL-17. The expression of MMP-9 (Matrix metalloproteinase-9) was however upregulated in both A. flavus and C. albicans infected microglia. These results indicate that microglial cells have the ability to incite an innate response towards endophthalmitis causing fungal pathogens via TLRs and inflammatory mediators. Moreover, our study highlights the differential responses of microglia towards yeast vs. filamentous fungi.

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