Effect of Krüppel-Like Factor 7 (KLF7) on High Sugar Induced Retinal Ganglion Cell Biological Activity and Oxidative Stress

2022 ◽  
Vol 12 (4) ◽  
pp. 788-793
Author(s):  
Lan Liu ◽  
Xinchao Cheng ◽  
Shaomin Li
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Biological Activity ◽  
Protein Expression ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Blank Group ◽  
High Sugar

This study investigated KLF7’s effect on sugar induced retinal ganglion cells (RGCs) biological activity. The RGCs cells divided into blank group (RA), high sugar group (RB), high sugar+NC group (RC) and high sugar+KLF7 group (RD) (transfected with KLF7 mimic) followed by analysis cell proliferation by MTT, cell apoptosis by flow cytometry and protein expression by western blot and ROS level. RB and RC group showed significantly reduced KLF7 mRNA and protein level compared to RA group (P < 0.05) without different between RB and RC group (P > 0.05). RD group had significantly increased LKF7 and Sirt1 protein expression (F = 113.3, P < 0.0, 01), reduced cell proliferation (P < 0.05) and increased RGCs apoptosis rate (P < 0.05) compared with RB and RC group. After 24 h, RB and RC group presented significantly higher ROS level (P < 0.05) which was reduced in RD group (P < 0.05). In conclusion, KLF7 can change sugar induced retinal ganglion cell biological activity and reduce the oxidative stress level.

scholarly journals Dynamic Expression of HDAC3 in db/db Mouse RGCs and Its Relationship with Apoptosis and Autophagy

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuhong Fu ◽  
Ying Wang ◽  
Xinyuan Gao ◽  
Huiyao Li ◽  
Yue Yuan
Keyword(s):  
Diabetic Retinopathy ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Control Group ◽  
Diabetic Patients ◽  
Retinal Ganglion ◽  
Glucose Levels ◽  
Dynamic Expression

Background. Diabetic retinopathy (DR) is a severe complication of diabetes mellitus. DR is considered as a neurovascular disease. Retinal ganglion cell (RGC) loss plays an important role in the vision function disorder of diabetic patients. Histone deacetylase3 (HDAC3) is closely related to injury repair and nerve regeneration. The correlation between HDAC3 and retinal ganglion cells in diabetic retinopathy is still unclear yet. Methods. To investigate the chronological sequence of the abnormalities of retinal ganglion cells in diabetic retinopathy, we choose 15 male db/db mice (aged 8 weeks, 12 weeks, 16 weeks, 18 weeks, and 25 weeks; each group had 3 mice) as diabetic groups and 3 male db/m mice (aged 8 weeks) as the control group. In this study, we examined the morphological and immunohistochemical changes of HDAC3, Caspase3, and LC3B in a sequential manner by characterizing the process of retinal ganglion cell variation. Results. Blood glucose levels and body weights of db/db mice were significantly higher than that of the control group, P<0.01. Compared with the control group, the number of retinal ganglion cells decreased with the duration of disease increasing. HDAC3 expression gradually increased in RGCs of db/db mice. Caspase3 expression gradually accelerated in RGCs of db/db mice. LC3B expression dynamically changed in RGCs of db/db mice. HDAC3 was positively correlated with Caspase3 expression (r=0.7424), P<0.01. HDAC3 was positively correlated with LC3B expression (r=0.7336), P<0.01. Discussion. We clarified the dynamic expression changes of HDAC3, Caspase3, and LC3B in retinal ganglion cells of db/db mice. Our results suggest the HDAC3 expression has a positive correlation with apoptosis and autophagy.

scholarly journals Neuroprotection of retinal ganglion cells by the sigma-1 receptor agonist pridopidine in models of experimental glaucoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michal Geva ◽  
Noga Gershoni-Emek ◽  
Luana Naia ◽  
Philip Ly ◽  
Sandra Mota ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Degeneration ◽  
Retinal Ganglion Cells ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Neuroprotective Effect ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Sigma 1 Receptor ◽  
Sigma 1

AbstractOptic neuropathies such as glaucoma are characterized by retinal ganglion cell (RGC) degeneration and death. The sigma-1 receptor (S1R) is an attractive target for treating optic neuropathies as it is highly expressed in RGCs, and its absence causes retinal degeneration. Activation of the S1R exerts neuroprotective effects in models of retinal degeneration. Pridopidine is a highly selective and potent S1R agonist in clinical development. We show that pridopidine exerts neuroprotection of retinal ganglion cells in two different rat models of glaucoma. Pridopidine strongly binds melanin, which is highly expressed in the retina. This feature of pridopidine has implications to its ocular distribution, bioavailability, and effective dose. Mitochondria dysfunction is a key contributor to retinal ganglion cell degeneration. Pridopidine rescues mitochondrial function via activation of the S1R, providing support for the potential mechanism driving its neuroprotective effect in retinal ganglion cells.

scholarly journals Bicycronic construct for optogenetic prosthesis of ganglion cell receptive field of degenerated retina

2019 ◽  
Vol 486 (2) ◽  
pp. 258-261
Author(s):  
L. E. Petrovskaya ◽  
M. V. Roshchin ◽  
G. R. Smirnova ◽  
D. E. Kolotova ◽  
P. M. Balaban ◽  
...  
Keyword(s):  
Receptive Field ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Distinctive Feature ◽  
Action Potentials ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Light Stimulation ◽  
Genetic Construct ◽  
Stimulation Of

For the purpose of optogenetic prosthetics of the receptive field of the retinal ganglion cell, we have created a bicistronic genetic construct that carries genes of excitatory (channelorhodopsin2) and inhibitory (anionic channelorhodopsin) rhodopsins. A distinctive feature of this construct is the combination of two genes into one construct with the mutant IRES inserted between them, which ensures precise ratio of the expression levels of the first and second gene in each transfected cell. It was found that the illumination of the central part of transfected neuron with light with a wavelength of 470 nm causes the generation of action potentials in the cell. At the same time, light stimulation of the periphery of the neuron causes cessation of the generation of action potentials. Thus, we were able to simulate the ON-OFF interaction of the receptive field of the retinal ganglion cell using optogenetic methods. Theoretically, this construction can be used for optogenetic prosthetics of degenerative retina in case of its delivery to ganglion cells using lentiviral vectors.

All Brn3 genes can promote retinal ganglion cell differentiation in the chick

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3237-3247 ◽  
Author(s):  
W. Liu ◽  
S.L. Khare ◽  
X. Liang ◽  
M.A. Peters ◽  
X. Liu ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Cell Development ◽  
Large Set ◽  
Retinal Ganglion ◽  
Pou Domain ◽  
Temporal Expression Pattern ◽  
Cell Genesis

Targeted gene disruption studies in the mouse have demonstrated crucial roles for the Brn3 POU domain transcription factor genes, Brn3a, Brn3b, Brn3c (now called Pou4f1, Pou4f2, Pou4f3, respectively) in sensorineural development and survival. During mouse retinogenesis, the Brn3b gene is expressed in a large set of postmitotic ganglion cell precursors and is required for their early and terminal differentiation. In contrast, the Brn3a and Brn3c genes, which are expressed later in ganglion cells, appear to be dispensable for ganglion cell development. To understand the mechanism that causes the functional differences of Brn3 genes in retinal development, we employed a gain-of-function approach in the chick embryo. We find that Brn3b(l) and Brn3b(s), the two isoforms encoded by the Brn3b gene, as well as Brn3a and Brn3c all have similar DNA-binding and transactivating activities. We further find that the POU domain is minimally required for these activities. Consequently, we show that all these Brn3 proteins have a similar ability to promote development of ganglion cells when ectopically expressed in retinal progenitors. During chick retinogenesis, cBrn3c instead of cBrn3b exhibits a spatial and temporal expression pattern characteristic of ganglion cell genesis and its misexpression can also increase ganglion cell production. Based on these data, we propose that all Brn3 factors are capable of promoting retinal ganglion cell development, and that this potential may be limited by the order of expression in vivo.

scholarly journals Midget retinal ganglion cell dendritic and mitochondrial degeneration is an early feature of human glaucoma

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
James R Tribble ◽  
Asta Vasalauskaite ◽  
Tony Redmond ◽  
Robert D Young ◽  
Shoaib Hassan ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Animal Models ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Face Scanning ◽  
Block Face ◽  
Scanning Electron

Abstract Glaucoma is characterized by the progressive dysfunction and loss of retinal ganglion cells. However, the earliest degenerative events that occur in human glaucoma are relatively unknown. Work in animal models has demonstrated that retinal ganglion cell dendrites remodel and atrophy prior to the loss of the cell soma. Whether this occurs in human glaucoma has yet to be elucidated. Serial block face scanning electron microscopy is well established as a method to determine neuronal connectivity at high resolution but so far has only been performed in normal retina from animal models. To assess the structure–function relationship of early human glaucomatous neurodegeneration, regions of inner retina assessed to have none-to-moderate loss of retinal ganglion cell number were processed using serial block face scanning electron microscopy (n = 4 normal retinas, n = 4 glaucoma retinas). This allowed detailed 3D reconstruction of retinal ganglion cells and their intracellular components at a nanometre scale. In our datasets, retinal ganglion cell dendrites degenerate early in human glaucoma, with remodelling and redistribution of the mitochondria. We assessed the relationship between visual sensitivity and retinal ganglion cell density and discovered that this only partially conformed to predicted models of structure–function relationships, which may be affected by these early neurodegenerative changes. In this study, human glaucomatous retinal ganglion cells demonstrate compartmentalized degenerative changes as observed in animal models. Importantly, in these models, many of these changes have been demonstrated to be reversible, increasing the likelihood of translation to viable therapies for human glaucoma.

scholarly journals Neuroprotective and Anti-Inflammatory Effects of a Hydrophilic Saffron Extract in a Model of Glaucoma

2019 ◽  
Vol 20 (17) ◽  
pp. 4110 ◽  
Author(s):  
Jose A. Fernández-Albarral ◽  
Ana I. Ramírez ◽  
Rosa de Hoz ◽  
Nerea López-Villarín ◽  
Elena Salobrar-García ◽  
...  
Keyword(s):  
Cell Death ◽  
Intraocular Pressure ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Retinal Ganglion Cell Death ◽  
Saffron Extract ◽  
Anti Inflammatory ◽  
Ganglion Cell Death

Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells (RGCs). An increase in the intraocular pressure is the principal risk factor for such loss, but controlling this pressure does not always prevent glaucomatous damage. Activation of immune cells resident in the retina (microglia) may contribute to RGC death. Thus, a substance with anti-inflammatory activity may protect against RGC degeneration. This study investigated the neuroprotective and anti-inflammatory effects of a hydrophilic saffron extract standardized to 3% crocin content in a mouse model of unilateral, laser-induced ocular hypertension (OHT). Treatment with saffron extract decreased microglion numbers and morphological signs of their activation, including soma size and process retraction, both in OHT and in contralateral eyes. Saffron extract treatment also partially reversed OHT-induced down-regulation of P2RY12. In addition, the extract prevented retinal ganglion cell death in OHT eyes. Oral administration of saffron extract was able to decrease the neuroinflammation associated with increased intraocular pressure, preventing retinal ganglion cell death. Our findings indicate that saffron extract may exert a protective effect in glaucomatous pathology.

scholarly journals Elevated ocular pressure reduces voltage-gated sodium channel NaV1.2 protein expression in retinal ganglion cell axons

2020 ◽  
Vol 190 ◽  
pp. 107873 ◽  
Author(s):  
Michael L. Risner ◽  
Nolan R. McGrady ◽  
Silvia Pasini ◽  
Wendi S. Lambert ◽  
David J. Calkins
Keyword(s):  
Protein Expression ◽  
Sodium Channel ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Retinal Ganglion ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Ocular Pressure

scholarly journals Mitochondrial pathogenic mechanism and degradation in optineurin E50K mutation-mediated retinal ganglion cell degeneration

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Myoung Sup Shim ◽  
Yuji Takihara ◽  
Keun-Young Kim ◽  
Takeshi Iwata ◽  
Beatrice Y. J. T. Yue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Open Angle Glaucoma ◽  
Mitochondrial Fission ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Transport Dynamics

Abstract Mutations in optineurin (OPTN) are linked to the pathology of primary open angle glaucoma (POAG) and amyotrophic lateral sclerosis. Emerging evidence indicates that OPTN mutation is involved in accumulation of damaged mitochondria and defective mitophagy. Nevertheless, the role played by an OPTN E50K mutation in the pathogenic mitochondrial mechanism that underlies retinal ganglion cell (RGC) degeneration in POAG remains unknown. We show here that E50K expression induces mitochondrial fission-mediated mitochondrial degradation and mitophagy in the axons of the glial lamina of aged E50K−tg mice in vivo. While E50K activates the Bax pathway and oxidative stress, and triggers dynamics alteration-mediated mitochondrial degradation and mitophagy in RGC somas in vitro, it does not affect transport dynamics and fission of mitochondria in RGC axons in vitro. These results strongly suggest that E50K is associated with mitochondrial dysfunction in RGC degeneration in synergy with environmental factors such as aging and/or oxidative stress.

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