scholarly journals The Interaction Between Microglia and Macroglia in Glaucoma

2021 ◽  
Vol 15 ◽  
Author(s):  
Xiaohuan Zhao ◽  
Rou Sun ◽  
Xueting Luo ◽  
Feng Wang ◽  
Xiaodong Sun
Keyword(s):  
Glial Cells ◽  
Vision Loss ◽  
Inflammatory Responses ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Treatment Options ◽  
Cell Types ◽  
Retinal Ganglion ◽  
Underlying Mechanisms ◽  
The Relationship

Glaucoma, a neurodegenerative disease that leads to irreversible vision loss, is characterized by progressive loss of retinal ganglion cells (RGCs) and optic axons. To date, elevated intraocular pressure (IOP) has been recognized as the main phenotypic factor associated with glaucoma. However, some patients with normal IOP also have glaucomatous visual impairment and RGC loss. Unfortunately, the underlying mechanisms behind such cases remain unclear. Recent studies have suggested that retinal glia play significant roles in the initiation and progression of glaucoma. Multiple types of glial cells are activated in glaucoma. Microglia, for example, act as critical mediators that orchestrate the progression of neuroinflammation through pro-inflammatory cytokines. In contrast, macroglia (astrocytes and Müller cells) participate in retinal inflammatory responses as modulators and contribute to neuroprotection through the secretion of neurotrophic factors. Notably, research results have indicated that intricate interactions between microglia and macroglia might provide potential therapeutic targets for the prevention and treatment of glaucoma. In this review, we examine the specific roles of microglia and macroglia in open-angle glaucoma, including glaucoma in animal models, and analyze the interaction between these two cell types. In addition, we discuss potential treatment options based on the relationship between glial cells and neurons.

scholarly journals Demyelination of the Optic Nerve: An Underlying Factor in Glaucoma?

2021 ◽  
Vol 13 ◽  
Author(s):  
Jingfei Xue ◽  
Yingting Zhu ◽  
Zhe Liu ◽  
Jicheng Lin ◽  
Yangjiani Li ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Ganglion Cells ◽  
Neuronal Degeneration ◽  
Retinal Ganglion ◽  
Progressive Degeneration ◽  
Treatment Plans ◽  
The Central Nervous System ◽  
The Relationship

Neurodegenerative disorders are characterized by typical neuronal degeneration and axonal loss in the central nervous system (CNS). Demyelination occurs when myelin or oligodendrocytes experience damage. Pathological changes in demyelination contribute to neurodegenerative diseases and worsen clinical symptoms during disease progression. Glaucoma is a neurodegenerative disease characterized by progressive degeneration of retinal ganglion cells (RGCs) and the optic nerve. Since it is not yet well understood, we hypothesized that demyelination could play a significant role in glaucoma. Therefore, this study started with the morphological and functional manifestations of demyelination in the CNS. Then, we discussed the main mechanisms of demyelination in terms of oxidative stress, mitochondrial damage, and immuno-inflammatory responses. Finally, we summarized the existing research on the relationship between optic nerve demyelination and glaucoma, aiming to inspire effective treatment plans for glaucoma in the future.

scholarly journals Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo

2016 ◽  
Vol 113 (25) ◽  
pp. E3492-E3500 ◽  
Author(s):  
Wei Zhu ◽  
Oliver W. Gramlich ◽  
Lauren Laboissonniere ◽  
Ankur Jain ◽  
Val C. Sheffield ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Large Fraction ◽  
Retinal Ganglion ◽  
Aqueous Humor Outflow ◽  
Induced Pluripotent

Glaucoma is a common cause of vision loss or blindness and reduction of intraocular pressure (IOP) has been proven beneficial in a large fraction of glaucoma patients. The IOP is maintained by the trabecular meshwork (TM) and the elevation of IOP in open-angle glaucoma is associated with dysfunction and loss of the postmitotic cells residing within this tissue. To determine if IOP control can be maintained by replacing lost TM cells, we transplanted TM-like cells derived from induced pluripotent stem cells into the anterior chamber of a transgenic mouse model of glaucoma. Transplantation led to significantly reduced IOP and improved aqueous humor outflow facility, which was sustained for at least 9 wk. The ability to maintain normal IOP engendered survival of retinal ganglion cells, whose loss is ultimately the cause for reduced vision in glaucoma. In vivo and in vitro analyses demonstrated higher TM cellularity in treated mice compared with littermate controls and indicated that this increase is primarily because of a proliferative response of endogenous TM cells. Thus, our study provides in vivo demonstration that regeneration of the glaucomatous TM is possible and points toward novel approaches in the treatment of this disease.

Mammalian Retinal Cell Quantification

2020 ◽  
pp. 019262332097637
Author(s):  
Anantharaman Muthuswamy ◽  
Henry Chen ◽  
Ying Hu ◽  
Oliver C. Turner ◽  
Olulanu H. Aina
Keyword(s):  
Vision Loss ◽  
Ganglion Cells ◽  
Cell Types ◽  
Age Related Macular Degeneration ◽  
Retinal Cell ◽  
Retinal Diseases ◽  
Retinal Ganglion ◽  
Retinal Cells ◽  
Cell Quantification ◽  
Age Related

Normal retina and its cell layers are essential for processing visual stimuli, and loss of its integrity has been documented in many disease processes. The numbers and the axonal processes of retinal ganglion cells are reduced substantially in glaucoma, leading to vision loss and blindness. Similarly, selective loss of photoreceptors in age-related macular degeneration and hereditary retinal dystrophies also results in the compromise of visual acuity. Development of genetically modified mice has led to increased understanding of the pathogenesis of many retinal diseases. Similarly, in this digital era, usage of modalities to quantify the retinal cell loss has grown exponentially leading to a better understanding of the suitability of animal models to study human retinal diseases. These quantification modalities provide valuable quantifiable data in studying pathogenesis and disease progression. This review will discuss the immunohistochemical markers for various retinal cells, available automated tools to quantify retinal cells, and present an example of retinal ganglion cell quantification using HALO image analysis platform. Additionally, we briefly review retinal cell types and subtypes, salient features of retina in various laboratory animal species, and a few of the main disease processes that affect retinal cell numbers in humans.

The Bulge Inflation Response of Bovine Sclera

2009 ◽  
Author(s):  
Kristin M. Myers ◽  
Thao D. Nguyen
Keyword(s):  
Visual Information ◽  
Vision Loss ◽  
Mechanical Response ◽  
Ganglion Cells ◽  
The United States ◽  
Retinal Ganglion ◽  
Tissue Samples ◽  
Strip Testing ◽  
The Relationship ◽  
The Brain

Glaucoma is one of the leading causes of blindness in the United States and in the world [1]. It is caused by damage to the retinal ganglion cells (RGC), a type of neuron that transmits visual information to the brain. Despite therapeutic efforts to reduce the rate of vision loss in glaucoma patients, the rate of blindness remains high [2]. There is evidence that elevated intraocular pressure (IOP) plays an important role in the damage to RGCs [3–5], but the relationship between the mechanical properties of the connective tissue and how it affects the cellular function is not understood. The load-bearing eye wall consists of the cornea and the sclera. Both tissues are collagen rich structures with preferentially aligned collagen lamellae dictating its mechanical response. Previous studies have shown that the viscoelastic material response of the eye wall differs between normal and glaucoma animal tissues [6]. However, these previous studies relied on strip testing of tissue samples.

Effect of dietary modification and antioxidant supplementation on intraocular pressure and open-angle glaucoma

2020 ◽  
pp. 112067212096033 ◽  
Author(s):  
Sayena Jabbehdari ◽  
Judy L Chen ◽  
Thasarat Sutabutr Vajaranant
Keyword(s):  
Oxidative Stress ◽  
Intraocular Pressure ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Cell Loss ◽  
Glaucomatous Optic Neuropathy ◽  
Retinal Ganglion ◽  
Open Angle ◽  
Modifiable Factor

Primary open-angle glaucoma (POAG) is an age-dependent, intraocular pressure (IOP)-related degeneration of the retinal ganglion cells (RGC). At present, IOP is the only modifiable factor that has been identified to prevent glaucomatous vision loss. Though the pathogenesis of glaucomatous optic neuropathy is still not well understood, increasing evidence suggests oxidative stress may contribute to the induction and progression of glaucoma. Furthermore, antioxidant use may be protective against glaucoma through various mechanisms, including reducing IOP, preserving vascular health, and preventing ganglion cell loss. This article provides a comprehensive review of the effect of oxidative stress, diet, and antioxidant therapy on IOP and open-angle glaucoma.

scholarly journals Predicting the genetic risk of glaucoma

2020 ◽  
Vol 42 (5) ◽  
pp. 26-30
Author(s):  
Ayub Qassim ◽  
Owen M Siggs
Keyword(s):  
Genetic Risk ◽  
Vision Loss ◽  
Primary Open Angle Glaucoma ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Healthcare Spending ◽  
Retinal Ganglion ◽  
Risk Variants ◽  
Risk Profiling ◽  
High Heritability

Glaucoma is the leading cause of irreversible blindness globally and is one of the most heritable human diseases. Labelled the ‘silent thief of sight’, primary open angle glaucoma is a progressive neurodegenerative disease of the retinal ganglion cells that can be treated by reducing intraocular pressure. Treatment is highly effective in preventing glaucoma vision loss; however, as it is asymptomatic in its early stages, many individuals with glaucoma are diagnosed only after a considerable amount of vision has already been lost. Given the high heritability of glaucoma, genetic risk profiling is now being explored as a way to identify individuals at the highest risk of developing glaucoma and those who will require the most intense treatment. Combining rare glaucoma-causing variants in single genes with more common genetic risk variants across many genes means that clinicians may soon be able to effectively stratify glaucoma risk across whole populations. This promises to maximize the efficiency of healthcare spending by prioritizing surveillance of high-risk individuals and reducing irreversible vision loss through early commencement of vision-saving treatments.

scholarly journals In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kolja Becker ◽  
Holger Klein ◽  
Eric Simon ◽  
Coralie Viollet ◽  
Christian Haslinger ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Expression Profiles ◽  
Cell Types ◽  
Sequencing Data ◽  
Disease Stages ◽  
Post Transcriptional Regulation

AbstractDiabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP–PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention.

Differences in nitric oxide production: a comparison of retinal ganglion cells and retinal glial cells cultured under hypoxic conditions

2003 ◽  
Vol 112 (1-2) ◽  
pp. 126-134 ◽  
Author(s):  
Kenji Kashiwagi ◽  
Yoko Iizuka ◽  
Seiichi Mochizuki ◽  
Yuichi Tsumamoto ◽  
Hiromu K Mishima ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Retinal Ganglion Cells ◽  
Glial Cells ◽  
Ganglion Cells ◽  
Nitric Oxide Production ◽  
Retinal Ganglion ◽  
Oxide Production ◽  
Hypoxic Conditions ◽  
Cells Cultured

scholarly journals Spatial receptive field properties of rat retinal ganglion cells

2011 ◽  
Vol 28 (5) ◽  
pp. 403-417 ◽  
Author(s):  
WALTER F. HEINE ◽  
CHRISTOPHER L. PASSAGLIA
Keyword(s):  
Receptive Field ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Cell Types ◽  
Quantitative Information ◽  
Retinal Ganglion ◽  
X And Y Cells ◽  
Y Cells

AbstractThe rat is a popular animal model for vision research, yet there is little quantitative information about the physiological properties of the cells that provide its brain with visual input, the retinal ganglion cells. It is not clear whether rats even possess the full complement of ganglion cell types found in other mammals. Since such information is important for evaluating rodent models of visual disease and elucidating the function of homologous and heterologous cells in different animals, we recorded from rat ganglion cells in vivo and systematically measured their spatial receptive field (RF) properties using spot, annulus, and grating patterns. Most of the recorded cells bore likeness to cat X and Y cells, exhibiting brisk responses, center-surround RFs, and linear or nonlinear spatial summation. The others resembled various types of mammalian W cell, including local-edge-detector cells, suppressed-by-contrast cells, and an unusual type with an ON–OFF surround. They generally exhibited sluggish responses, larger RFs, and lower responsiveness. The peak responsivity of brisk-nonlinear (Y-type) cells was around twice that of brisk-linear (X-type) cells and several fold that of sluggish cells. The RF size of brisk-linear and brisk-nonlinear cells was indistinguishable, with average center and surround diameters of 5.6 ± 1.3 and 26.4 ± 11.3 deg, respectively. In contrast, the center diameter of recorded sluggish cells averaged 12.8 ± 7.9 deg. The homogeneous RF size of rat brisk cells is unlike that of cat X and Y cells, and its implication regarding the putative roles of these two ganglion cell types in visual signaling is discussed.

Development of cholinergic amacrine cell stratification in the ferret retina and the effects of early excitotoxic ablation

2001 ◽  
Vol 18 (4) ◽  
pp. 559-570 ◽  
Author(s):  
B.E. REESE ◽  
M.A. RAVEN ◽  
K.A. GIANNOTTI ◽  
P.T. JOHNSON
Keyword(s):  
Ganglion Cell ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Cell Types ◽  
Retinal Cell ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Outer Border ◽  
Cholinergic Amacrine Cells

The present study has examined the emergence of cholinergic stratification within the developing inner plexiform layer (IPL), and the effect of ablating the cholinergic amacrine cells on the formation of other stratifications within the IPL. The population of cholinergic amacrine cells in the ferret's retina was identified as early as the day of birth, but their processes did not form discrete strata until the end of the first postnatal week. As development proceeded over the next five postnatal weeks, so the positioning of the cholinergic strata shifted within the IPL toward the outer border, indicative of the greater ingrowth and elaboration of processes within the innermost parts of the IPL. To examine whether these cholinergic strata play an instructive role upon the development of other stratifications which form within the IPL, one-week-old ferrets were treated with l-glutamate in an attempt to ablate the population of cholinergic amacrine cells. Such treatment was shown to be successful, eliminating all of the cholinergic amacrine cells as well as the alpha retinal ganglion cells in the central retina. The remaining ganglion cell classes as well as a few other retinal cell types were partially reduced, while other cell types were not affected, and neither retinal histology nor areal growth was compromised in these ferrets. Despite this early loss of the cholinergic amacrine cells, which are eliminated within 24 h, other stratifications within the IPL formed normally, as they do following early elimination of the entire ganglion cell population. While these cholinergic amacrine cells are present well before other cell types have differentiated, apparently neither they, nor the ganglion cells, play a role in determining the depth of stratification for other retinal cell types.

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