Mechanism of Propofol-Lidocaine Hydrochloride Nano-Emulsion on Retinal Ganglion Cytopathic Effect in Diabetic Rats

2022 ◽  
Vol 12 (1) ◽  
pp. 36-44
Author(s):  
He Zhang ◽  
Wenli Dong ◽  
Chao Long ◽  
Qingchun Li
Keyword(s):  
Particle Size ◽  
Blood Glucose ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Test Group ◽  
Lidocaine Hydrochloride ◽  
Control Group ◽  
Mrna Levels ◽  
Retinal Ganglion ◽  
Model Group

The study drew attention to the influence mechanism of propofol and lidocaine hydrochloride nanoemulsion (NE) in the retinal ganglion cell pathology in diabetic rats. Specifically, the propofollidocaine hydrochloride NE was prepared using the emulsification method. The microscope and laser particle size analyser were used to observe the morphology and particle size of NE, respectively. Also, the viscosity of the NE and the recovery rate of the main ingredient were explored. 45 adult male Wistar rats were randomly divided into control group (PBS control), model group (diabetes model), and test group (diabetes model+propofol-lidocaine hydrochloride NE), with 15 rats in each group. The three groups were compared for the blood glucose, body weight, TNF-α and IL-1β mRNA levels in retinal tissue, and the number and apoptosis rate of ganglion cells. It was found that the average particle size of the NE was 89.76 nm, the maximum absorption wavelength was 280.0 nm, and the viscosity was 106.49 N/m/s. The average recovery rate of propofol in NE was 99.91%, and that of lidocaine hydrochloride was 99.80%. At 12th week after modeling, the blood glucose of the test group was lower versus the model group (P < 0.05); the blood glucose and body weight of rats in the control group were lower than those in the other two groups (P < 0.001). The test group exhibited lower mRNA levels of TNF-α and IL-1β and apoptosis index of retinal ganglion cells versus the model group (P < 0.05). The model group showed a lower number of retinal ganglion cells versus the other two groups (P < 0.05). It was inferred that propofol-lidocaine hydrochloride NE of a small particle size and good syringeability can notably reduce blood glucose, TNF-α and IL-1β mRNA levels, and retinal ganglion cell apoptosis index, and at the same time increase the number of retinal ganglion cells.

scholarly journals Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage

2021 ◽  
Vol 12 ◽  
Author(s):  
Federica Conti ◽  
Giovanni Luca Romano ◽  
Chiara Maria Eandi ◽  
Mario Damiano Toro ◽  
Robert Rejdak ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Inflammatory Markers ◽  
Ganglion Cells ◽  
Mouse Retina ◽  
Control Group ◽  
Mrna Levels ◽  
Retinal Ganglion ◽  
Bdnf Mrna ◽  
Wide Range ◽  
Anti Inflammatory

To investigate the neuroprotective effect of brimonidine after retinal ischemia damage on mouse eye. Glaucoma is an optic neuropathy characterized by retinal ganglion cells (RGCs) death, irreversible peripheral and central visual field loss, and high intraocular pressure. Ischemia reperfusion (I/R) injury model was used in C57BL/6J mice to mimic conditions of glaucomatous neurodegeneration. Mouse eyes were treated topically with brimonidine and pattern electroretinogram were used to assess the retinal ganglion cells (RGCs) function. A wide range of inflammatory markers, as well as anti-inflammatory and neurotrophic molecules, were investigated to figure out the potential protective effects of brimonidine in mouse retina. In particular, brain-derived neurotrophic factor (BDNF), IL-6, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptor DR-5, TNF-α, GFAP, Iba-1, NOS, IL-1β and IL-10 were assessed in mouse retina that underwent to I/R insult with or without brimonidine treatment. Brimonidine provided remarkable RGCs protection in our paradigm. PERG amplitude values were significantly (p &lt; 0.05) higher in brimonidine-treated eyes in comparison to I/R retinas. Retinal BDNF mRNA levels in the I/R group dropped significantly (p &lt; 0.05) compared to the control group (normal mice); brimonidine treatment counteracted the downregulation of retinal BDNF mRNA in I/R eyes. Retinal inflammatory markers increased significantly (p &lt; 0.05) in the I/R group and brimonidine treatment was able to revert that. The anti-inflammatory IL-10 decreased significantly (p &lt; 0.05) after retinal I/R insult and increased significantly (p &lt; 0.05) in the group treated with brimonidine. In conclusion, brimonidine was effective in preventing loss of function of RGCs and in regulating inflammatory biomarkers elicited by retinal I/R injury.

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.

The Photopic Negative Response evaluation in patients with Leber's hereditary optic neuropathy

2021 ◽  
pp. 216-219
Author(s):  
M.S. Shmelkova ◽  
◽  
N.L. Sheremet ◽  
I.A. Ronzina ◽  
N.A. Andreeva ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Retinal Ganglion Cells ◽  
Optic Neuropathy ◽  
Ganglion Cells ◽  
Negative Response ◽  
Photopic Negative Response ◽  
Control Group ◽  
Retinal Ganglion ◽  
Leber's Hereditary Optic Neuropathy ◽  
Hereditary Optic Neuropathy

Purpose. To assess the retinal ganglion cells function in patients with Leber's hereditary optic neuropathy (LHON) by registering the photopic negative response (PhNR) while the photopic electroretinography is performed. Material and methods. 14 patients with different LHON mutations and 9 healthy individuals were examined. A standard ophtalmological examination was performed, including visual fields, spectral optical coherence tomography, photopic electroretinography and PhNR tests. Results. Significant differences in the PhNR latency (68.4±4.01/64.28±5.37, p<0,01) and the PhNR amplitude (21.5±9.34/32.72±12.73, p<0,003) were revealed in patients with LHON and the control group. The study revealed significant differences between the PhNR latency (р<0.01) and the PhNR amplitude (р<0.008) in patients with visual acuity (VA) ≤ 0.1 and the control group, and between the PhNR amplitude in patients with VA≥0.13 and the control group (р<0.05). There were found significant correlations between the PhNR parameters and visual acuity, mean sensitivity, RNFL and GCC thickness. A strong positive correlation was found between the PhNR amplitude and the GCC thickness in patients with VA≥0.3. Conclusion. The PhNR parameters reflect the retinal ganglion cells function in patients with LHON and correlate with RNFL and GCC structural changes. Key words: Leber hereditary optic neuropathy, mitochondrial optical neuropathies, retinal ganglion cell, photopic negative response, PhNR.

scholarly journals Lepidium sativum as candidate against excitotoxicity in retinal ganglion cells

2021 ◽  
Vol 12 (1) ◽  
pp. 247-259
Author(s):  
Abeer Al-Dbass ◽  
Musarat Amina ◽  
Nawal M. Al Musayeib ◽  
Amira A. El-Anssary ◽  
Ramesa Shafi Bhat ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Cell Damage ◽  
Tail Length ◽  
Glutamate Excitotoxicity ◽  
Control Group ◽  
Retinal Ganglion ◽  
Blank Control Group

Abstract Glutamate excitotoxicity is considered one of the major causes of retinal ganglion cell death in many retinal diseases. Retinal ganglion cell degeneration causes severe blindness since visual signals from the eye to the brain are conducted only through retinal ganglion cells. Objective: We aimed to explore the potential ameliorative effects of L. sativum against glutamate excitotoxicity-induced retinal ganglion cell damage. Methods: Pure retinal ganglion cells were divided into a control group (untreated); L. sativum-treated groups in which retinal ganglion cells were treated with 5, 10, 50, or 100 µg/mL L. sativum seed extract for 2 h; glutamate-treated groups in which cells were treated with 5, 10, 50, or 100 µM glutamate for 48 h; and L. sativum/glutamate groups [pretreatment with L. sativum for 2 h (50 or 100 µg/mL) before glutamate treatment at 100 µM for 48 h]. Cell damage was assessed by comet assay and cell viability was by MTT test. Results: Tailed DNA, tail length, and tail moment of the 50 and 100 mM glutamate-treated groups were significantly greater than those of the blank control group, while the L. sativum-treated groups demonstrated nonsignificantly different tailed DNA, tail length, and tail moment compared with the blank control group, but significantly lower values compared with the glutamate-treated groups. Conclusion: L. sativum ameliorated the cell viability in retinal ganglion cells after high-concentration glutamate exposure. L. sativum seed extracts were efficient anti-excitotoxic and antioxidant agent that might improve the clinical presentation of many neurological disorders.

scholarly journals Oxidative stress and mitochondrial dysfunction of retinal ganglion cells injury exposures in long-term blue light

2020 ◽  
Vol 13 (12) ◽  
pp. 1854-1863
Author(s):  
Ke-Xin Guo ◽  
Wei Wang ◽  
Pei Zhang ◽  
Ying Li ◽  
Zi-Yuan Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Retinal Ganglion Cells ◽  
Blue Light ◽  
Narrow Band ◽  
Ganglion Cells ◽  
Control Group ◽  
Retinal Ganglion ◽  
Metabolic Remodeling

AIM: To investigate the phototoxic effect of long-term excessive narrow-band blue light in staurosporine-induced differentiated retinal ganglion cells-5 (SSRGC-5). METHODS: SSRGC-5 cells were divided into two groups, blue light group (BL group) and control group. Cell viability was assessed by using CCK-8 assay. Metabolic profile analysis was performed by using Seahorse extracellular flux analyzer. Mitochondria ultrastructure were studied via transmission electron microscope (TEM). Mitochondria contents and oxidative stress was evaluated by flow cytometry. Western blotting was performed to monitor the changes in mitogen-activated protein kinases (MAPK) pathway and PI3K/AKT pathway. RESULTS: Blue light caused morphological changes of SSRGC-5 cells. The cell viability was significantly decreased from 3h in BL group. Intercellular ROS and mitochondrial superoxide levels were increased following blue light exposure. Metabolic profiling identified blue light induced SSRGC-5 cells to have severely compromised mitochondrial function. This was accompanied by impaired mitochondrial ultrastructure and remodeling, increased expression of the mitochondrial related proteins, and increased glycolysis as compensation. Moreover, the results showed that blue light induced higher expression of p-p38, p38, p-JNK, p-ERK, p-c-Jun, c-Jun, and p-AKT. CONCLUSION: These findings indicate that excessive narrow-band blue light induces oxidative stress and mitochondrial metabolic remodeling dysregulate in SSRGC-5 cells. Activated MAPK and AKT signaling pathways are involved in this process.

scholarly journals MiR-124 Promotes the Growth of Retinal Ganglion Cells Derived from Müller Cells

2018 ◽  
Vol 45 (3) ◽  
pp. 973-983 ◽  
Author(s):  
Ye He ◽  
Hai-bo Li ◽  
Xin Li ◽  
Yi Zhou ◽  
Xiao-bo Xia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Axon Growth ◽  
Müller Cells ◽  
Luciferase Assay ◽  
Control Group ◽  
Retinal Ganglion ◽  
Muller Cells ◽  
Retinal Stem Cells

Background/Aims: Retinal Müller cells could be induced to differentiate into retinal ganglion cells (RGCs), but RGCs derived from Müller cells have defects in axon growth, leading to a defect in signal conduction. In this study we aimed to explore the role of miR-124 in axon growth of RGCs derived from Müller cells. Methods: Müller cells were isolated from rat retina and induced to dedifferentiate into retinal stem cells. The stem cells were infected by PGC-FU-Atoh7-GFP lentivirus and then transfected with miR-124 or anti-miR-124, and the length of axon was compared. Furthermore, the cells were injected into the eyes of rat chronic ocular hypertension glaucoma model and axon growth in vivo was examined. The targeting of CoREST by miR-124 was detected by luciferase assay. Results: In retinal stem cells, the length of axon was 1,792±64.54 µm in miR-124 group, 509±21.35 µm in control group, and only 87.9±9.24 µm in anti-miR-124 group. In rat model, miR-124 promoted axon growth of RGCs differentiated from retinal stem cells. Furthermore, we found that miR-124 negatively regulated CoREST via directly targeting the binding site in CoREST 3′ UTR. Conclusions: We provide the first evidence that miR-124 regulates axon growth of RGCs derived from Müller cells, and miR-124 has translational potential for gene therapy of glaucoma.

Function and spatial distribution in developing chick retina of the laminin receptor alpha 6 beta 1 and its isoforms

Development ◽  
1993 ◽  
Vol 118 (2) ◽  
pp. 377-388 ◽  
Author(s):  
I. de Curtis ◽  
L.F. Reichardt
Keyword(s):  
Retinal Ganglion Cells ◽  
Optic Tectum ◽  
Ganglion Cells ◽  
Laminin Receptor ◽  
Mrna Levels ◽  
Retinal Ganglion ◽  
Retinal Cells ◽  
Retina Development ◽  
Receptor Alpha ◽  
Chick Retina

We have recently shown that the laminin-binding integrin receptor, alpha 6 beta 1, is prominently expressed in the developing chick retina, and its expression and activity are regulated during development on both retinal ganglion cells and other neural retinal cells. In the present study, we show that antibodies specific for the extracellular portion of the chick alpha 6 subunit dramatically inhibit interactions in vitro between embryonic day 6 neural retinal cells and laminin, showing that alpha 6 beta 1 functions as an important laminin receptor on developing retinal neurons. In previous work, we showed that alpha 6 mRNA levels on retinal ganglion cells decrease dramatically after E6 during the period that RGC axons innervate the optic tectum. In the present study, we show decreases in alpha 6 mRNA are not prevented by ablation of the optic tectum, indicating that tectal contact is not the major cause of this decrease. Within the embryonic retina, the alpha 6 subunit is codistributed, in part, with laminin, suggesting that it functions as a laminin receptor during retina development in vivo. Furthermore, two isoforms of the alpha 6 protein with distinct cytoplasmic domains generated by differential splicing have quite different distribution patterns in the retina, suggesting that these two isoforms may have different functions during retinal development.

Involvement of Upregulated P53-Induced Death Domain Protein in Retinal Ganglion Cells Apoptosis After Optic Nerve Crush

2019 ◽  
Vol 20 (1) ◽  
pp. 51-59
Author(s):  
Mingyuan Zhang ◽  
Lifei Chen ◽  
Fan Xu ◽  
Li Jiang ◽  
Wenya Yan ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Control Group ◽  
Optic Nerve Crush ◽  
Retinal Ganglion ◽  
Death Domain ◽  
Nerve Crush ◽  
Caspase 2 ◽  
Sirna Group

Purpose: Retinal ganglion cells (RGCs) apoptosis is a common characteristic of optic neuropathies. p53-induced protein with a death domain (PIDD) is a well-known regulator of genotoxic stress-induced apoptosis, which is constitutively cleaved into three main fragments: PIDD-N, PIDD-C and PIDD-CC. Thus, we aim to determine the physiological relevance of PIDD in RGCs apoptosis in an optic nerve crush (ONC) model. Methods: All animals were evenly randomized into four groups: sham-control group, con-siRNA group, ONC group, and PIDD-siRNA group (ONC +PIDD-siRNA). Expressions of PIDD, caspase-2, Brn3a and tBid in ONC model were analyzed by Western blot and immunofluorescence. Mean densities of RGCs/mm2 were calculated with Fluoro-Gold (FG). Moreover, we tested the effect of PIDD-siRNA on ONC-induced RGCs apoptosis using TUNEL staining. Results: The level of full-length PIDD was weakly present and showed no significant differences at any time points. PIDD-CC and PIDD-C were significantly up-regulated in the retina at 3 days after ONC. Meanwhile, the expression of PIDD was significantly increased in Brn3a (a marker of RGCs) positive cells, indicating that the localization of PIDD appeared to be confined to RGCs. Furthermore, inhibition of PIDD prevented RGCs apoptosis by inhibiting caspase-2 and tBid activation. Conclusions: Taken together, PIDD may play a crucial role in RGCs apoptosis after ONC, and this process may be relevant to caspase-2 and tBid.

scholarly journals 1α,25-dihydroxyvitamin D3 protects retinal ganglion cells in glaucomatous mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Francesca Lazzara ◽  
Rosario Amato ◽  
Chiara Bianca Maria Platania ◽  
Federica Conti ◽  
Tsung-Han Chou ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Inflammatory Cytokines ◽  
Genetic Model ◽  
Ganglion Cells ◽  
Statistical Tests ◽  
Pattern Electroretinogram ◽  
Mrna Levels ◽  
Retinal Ganglion ◽  
Astrocyte Activation ◽  
Age Related

Abstract Background Glaucoma is an optic neuropathy characterized by loss of function and death of retinal ganglion cells (RGCs), leading to irreversible vision loss. Neuroinflammation is recognized as one of the causes of glaucoma, and currently no treatment is addressing this mechanism. We aimed to investigate the anti-inflammatory and neuroprotective effects of 1,25(OH)2D3 (1α,25-dihydroxyvitamin D3, calcitriol), in a genetic model of age-related glaucomatous neurodegeneration (DBA/2J mice). Methods DBA/2J mice were randomized to 1,25(OH)2D3 or vehicle treatment groups. Pattern electroretinogram, flash electroretinogram, and intraocular pressure were recorded weekly. Immunostaining for RBPMS, Iba-1, and GFAP was carried out on retinal flat mounts to assess retinal ganglion cell density and quantify microglial and astrocyte activation, respectively. Molecular biology analyses were carried out to evaluate retinal expression of pro-inflammatory cytokines, pNFκB-p65, and neuroprotective factors. Investigators that analysed the data were blind to experimental groups, which were unveiled after graph design and statistical analysis, that were carried out with GraphPad Prism. Several statistical tests and approaches were used: the generalized estimated equations (GEE) analysis, t-test, and one-way ANOVA. Results DBA/2J mice treated with 1,25(OH)2D3 for 5 weeks showed improved PERG and FERG amplitudes and reduced RGCs death, compared to vehicle-treated age-matched controls. 1,25(OH)2D3 treatment decreased microglial and astrocyte activation, as well as expression of inflammatory cytokines and pNF-κB-p65 (p < 0.05). Moreover, 1,25(OH)2D3-treated DBA/2J mice displayed increased mRNA levels of neuroprotective factors (p < 0.05), such as BDNF. Conclusions 1,25(OH)2D3 protected RGCs preserving retinal function, reducing inflammatory cytokines, and increasing expression of neuroprotective factors. Therefore, 1,25(OH)2D3 could attenuate the retinal damage in glaucomatous patients and warrants further clinical evaluation for the treatment of optic neuropathies.

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