scholarly journals Cytidine 5′-Diphosphocholine (Citicoline): Evidence for a Neuroprotective Role in Glaucoma

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 793 ◽  
Author(s):  
Stefano Gandolfi ◽  
Giorgio Marchini ◽  
Aldo Caporossi ◽  
Gianluca Scuderi ◽  
Livia Tomasso ◽  
...  
Keyword(s):  
Visual Field ◽  
Therapeutic Agent ◽  
Primary Open Angle Glaucoma ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Brain Structures ◽  
Current Evidence ◽  
Retinal Ganglion ◽  
Naturally Occurring ◽  
Endogenous Compound

Glaucoma, a heterogeneous set of progressively degenerative optic neuropathies characterized by a loss of retinal ganglion cells (RGCs) and typical visual field deficits that can progress to blindness, is a neurodegenerative disease involving both ocular and visual brain structures. Although elevated intraocular pressure (IOP) remains the most important modifiable risk factor of primary open-angle glaucoma (POAG) and is the main therapeutic target in treating glaucoma, other factors that influence the disease course are involved and reaching the optimal IOP target does not stop the progression of glaucoma, as the visual field continues to narrow. In addition to a managed IOP, neuroprotection may be beneficial by slowing the progression of glaucoma and improving the visual defects. Citicoline (cytidine 5′-diphosphocholine) is a naturally occurring endogenous compound that has been investigated as a novel therapeutic agent for the management of glaucoma. Citicoline has demonstrated activity in a range of central neurodegenerative diseases, and experimental evidence suggests a it performs a neuromodulator and neuroprotective role on neuronal cells, including RGCs, associated with improvement in visual function, extension of the visual field and central benefits for the patient. This review aims to critically summarize the current evidence for the neuroprotective properties of citicoline in glaucoma.

scholarly journals Stem cell transplantation rescued a primary open-angle glaucoma mouse model

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Siqi Xiong ◽  
Ajay Kumar ◽  
Shenghe Tian ◽  
Eman E Taher ◽  
Enzhi Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mouse Model ◽  
Retinal Ganglion Cells ◽  
Primary Open Angle Glaucoma ◽  
Therapeutic Potential ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Retinal Ganglion ◽  
Upregulated Genes

Glaucoma is a leading cause of irreversible blindness. In this study, we investigated if transplanted stem cells are able to rescue a glaucoma mouse model with transgenic myocilin Y437H mutation and explored the possible mechanisms. Human trabecular meshwork stem cells (TMSCs) were intracamerally transplanted which reduced mouse intraocular pressure, increased outflow facility, protected the retinal ganglion cells and preserved their function. TMSC transplantation also significantly increased the TM cellularity, promoted myocilin secretion from TM cells into the aqueous humor to reduce endoplasmic reticulum stress, repaired the TM tissue with extracellular matrix modulation and ultrastructural restoration. Co-culturing TMSCs with myocilin mutant TM cells in vitro promoted TMSCs differentiating into phagocytic functional TM cells. RNA sequencing revealed that TMSCs had upregulated genes related to TM regeneration and neuroprotection. Our results uncovered therapeutic potential of TMSCs for curing glaucoma and elucidated possible mechanisms by which TMSCs achieve the treatment effect.

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 Stem Cell Transplantation Rescued A Primary Open-Angle Glaucoma Mouse Model

2020 ◽  
Author(s):  
Siqi Xiong ◽  
Ajay Kumar ◽  
Shenghe Tian ◽  
Eman E. Taher ◽  
Enzhi Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mouse Model ◽  
Retinal Ganglion Cells ◽  
Primary Open Angle Glaucoma ◽  
Therapeutic Potential ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Retinal Ganglion ◽  
Upregulated Genes

AbstractGlaucoma is a leading cause of irreversible blindness. In this study, we investigated if exogenous stem cells are able to rescue a glaucoma mouse model with transgenic myocilin Y437H mutation and explored the possible mechanisms. Human trabecular meshwork stem cells (TMSCs) were intracamerally transplanted which reduced mouse intraocular pressure, increased outflow facility, protected the retinal ganglion cells and preserved their function. TMSC transplantation also significantly increased the TM cellularity, promoted myocilin secretion from TM cells into the aqueous humor to reduce endoplasmic reticulum stress, repaired the TM tissue with extracellular matrix modulation and ultrastructural restoration. Co-culturing TMSCs with myocilin mutant TM cells in vitro promoted TMSCs differentiating into phagocytic functional TM cells. RNA sequencing revealed that TMSCs had upregulated genes related to TM regeneration and neuroprotection. Our results uncovered therapeutic potential of TMSCs for curing glaucoma and elucidated possible mechanisms by which TMSCs achieve the treatment effect.

scholarly journals Some Aspects of Vascular Theory of Development and Progression of Primary Open-Angle Glaucoma (Literature Review). Part 1

2019 ◽  
Vol 16 (1) ◽  
pp. 12-18
Author(s):  
S. I. Makogon ◽  
A. S. Makogon
Keyword(s):  
Primary Open Angle Glaucoma ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Vascular Wall ◽  
Biologically Active ◽  
Retinal Ganglion ◽  
Open Angle ◽  
Hemostatic System ◽  
Plasma Proteolytic Systems ◽  
The Impact

The article presents a review of studies on various aspects of vascular theory of primary open-angle glaucoma (POAG) development and progression. The data of foreign and domestic scientists on the influence of hemodynamic disturbances in the glaucoma pathogenesis, including various levels: Central, regional and microcirculatory. Violations of the universal mechanism of vascular tone regulation, namely endothelial dysfunction are described. Vascular endothelium is a barrier between vascular wall and blood plasma. When the endothelium is damaged, its antithrombotic properties are transformed into a powerful prothrombotic potential. This leads to an imbalance between vasoconstrictors (endothelin) and vasodilators (nitric oxide). In addition, the release of biologically active substances with local neurotoxic effects. The authors noted an increase in the concentration of endothelin-1, studied its interaction with nitrogen oxide and considered its role in the occurrence of ischemia and the impact on the death of retinal ganglion cells. Scientists have noticed an increase in the level of Willebrand factor and increased platelet aggregation in patients with progressive glaucoma. As a possible cause of hemodynamic disturbances and glaucoma progression, the authors consider changes in blood rheological properties. In addition, the state of the three closely interacting components: the wall of blood vessels (primarily endothelium and subendothelial structures); cellular elements of blood (primarily platelets) and plasma proteolytic systems ensure the normal functioning of the hemostatic system. Changes in of these components state may affect the hemostatic system. Therefore, further study of various directions of vascular theory will help in understanding the etiopathogenesis of glaucoma.

scholarly journals Genomic Locus Modulating Corneal Thickness in the Mouse Identifies POU6F2 as a Potential Risk of Developing Glaucoma

2017 ◽  
Author(s):  
Rebecca King ◽  
Felix L. Struebing ◽  
Ying Li ◽  
Jiaxing Wang ◽  
Allison Ashley Koch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Retinal Ganglion Cells ◽  
Central Corneal Thickness ◽  
Primary Open Angle Glaucoma ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Corneal Thickness ◽  
Retinal Ganglion ◽  
Open Angle

AbstractPurpose: Central corneal thickness (CCT) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma (POAG). The present study uses the BXD Recombinant Inbred (RI) strains to identify novel quantitative trait loci (QTLs) modulating CCT in the mouse with the potential of identifying a molecular link between CCT and risk of developing POAG.Methods: The BXD RI strain set was used to define mammalian genomic loci modulating CCT, with a total of 818 corneas measured from 61 BXD RI strains (between 60-100 days of age). The mice were anesthetized and the eyes were positioned in front of the lens of the Phoenix Micron IV Image-Guided OCT system or the Bioptigen OCT system. CCT data for each strain was averaged and used to identify quantitative trait loci (QTLs) modulating this phenotype using the bioinformatics tools on GeneNetwork (www.genenetwork.org). The candidate genes and genomic loci identified in the mouse were then directly compared with the summary data from a human primary open-angle glaucoma (POGA) genome wide association study (NEIGHBORHOOD) to determine if any genomic elements modulating mouse CCT are also risk factors for POAG.Results: This analysis revealed one significant QTL on Chr 13 and a suggestive QTL on Chr 7. The significant locus on Chr 13 (13 to 19 Mb) was examined further to define candidate genes modulating this eye phenotype. For the Chr 13 QTL in the mouse, only one gene in the region (Pou6f2) contained nonsynonymous SNPs. Of these five nonsynonymous SNPs in Pou6f2, two resulted in changes in the amino acid proline which could result in altered secondary structure affecting protein function. The 7 Mb region under the mouse Chr 13 peak distributes over 2 chromosomes in the human: Chr 1 and Chr 7. These genomic loci were examined in the NEIGHBORHOOD database to determine if they are potential risk factors for human glaucoma identified using meta-data from human GWAS. The top 50 hits all resided within one gene (POU6F2), with the highest significance level of p = 10−6 for SNP rs76319873. POU6F2 is found in retinal ganglion cells and in corneal limbal stem cells. To test the effect of POU6F2 on CCT we examined the corneas of a Pou6f2-null mice and the corneas were thinner than those of wild-type littermates. In addition, these POU6F2 RGCs die early in the DBA/2J model of glaucoma than most RGCs.Conclusions: Using a mouse genetic reference panel, we identified a transcription factor, Pou6f2, that modulates CCT in the mouse. POU6F2 is also found in a subset of retinal ganglion cells and these RGCs are sensitive to injury.Authors SummaryGlaucoma is a complex group of diseases with several known causal mutations and many known risk factors. One well-known risk factor for developing primary open angle glaucoma is the thickness of the central cornea. The present study leverages a unique blend of systems biology methods using BXD recombinant inbred mice and genome-wide association studies from humans to define a putative molecular link between a phenotypic risk factor (central corneal thickness) and glaucoma. We identified a transcription factor, POU6F2, that is found in the developing retinal ganglion cells and cornea. POU6F2 is also present in a subpopulation of retinal ganglion cells and in stem cells of the cornea. Functional studies reveal that POU6F2 is associated the central corneal thickness and with susceptibility of retinal ganglion cells to injury.

CITICOLINE APPLICATIONS AS A COMPLEX PRIMARY TREATMENT

2020 ◽  
Vol 6 (1) ◽  
pp. 18-22
Author(s):  
Kh. Abulkasimova ◽  
◽  
M. Karimova
Keyword(s):  
Retinal Ganglion Cells ◽  
Primary Open Angle Glaucoma ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Primary Treatment ◽  
Retinal Ganglion ◽  
Open Angle ◽  
Complex Therapy ◽  
Stabilizing Effect ◽  
Lipid Balance

This article is about primary open-angle glaucoma (POAG) which is a multifactorial degenerative disease that affects the optic nerve and subsequently leads to the loss of retinal ganglion cells (RGC) and their axons. Therefore, preparations with antioxidant and membrane-stabilizing effect, as well as ensuring restoration of lipid balance, are relevant in the complex therapy of POAG.

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.

Determining Heterogeneity in the Scleral Shell Using an Inverse Mechanics Approach

2013 ◽  
Author(s):  
Avinash Ayyalasomayajula ◽  
Jonathan Vande Geest
Keyword(s):  
Race And Ethnicity ◽  
Visual Information ◽  
Primary Open Angle Glaucoma ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Retinal Ganglion ◽  
Ocular Tissues ◽  
The Us ◽  
Elevated Intraocular Pressure ◽  
Scleral Shell

One of the important events leading to loss of vision in primary open-angle glaucoma — the 2 nd leading cause of blindness in the US [1] — is the death of retinal ganglion cells. Previous research has established a strong correlation between elevated intraocular pressure (IOP) and the incidence of glaucoma [2]. Stiffening of ocular tissues (like sclera) and axonal damage in the optic nerve head (ONH) were found to occur in response to elevated IOPs [3, 4]. As such, the biomechanical environment in and around the ONH, which is surrounded by the sclera and through which the visual information exits the eye, could be important in the incidence of this disease. Additionally, race and ethnicity factors were found to affect the incidence of glaucoma [5].

scholarly journals Loss of retinal ganglion cells in a new genetic mouse model for primary open‐angle glaucoma

2019 ◽  
Vol 23 (8) ◽  
pp. 5497-5507 ◽  
Author(s):  
Sabrina Reinehr ◽  
Dennis Koch ◽  
Maximilian Weiss ◽  
Franziska Froemel ◽  
Christina Voss ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinal Ganglion Cells ◽  
Primary Open Angle Glaucoma ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Retinal Ganglion ◽  
Open Angle ◽  
Genetic Mouse Model
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