Cell-Based Neuroprotection of Retinal Ganglion Cells in Animal Models of Optic Neuropathies

Hu, Yue; Grodzki, Lynn Michelle; Bartsch, Susanne; Bartsch, Udo

doi:10.3390/biology10111181

Cited by 3 publications

(3 citation statements)

References 185 publications

(271 reference statements)

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“…The pathophysiology of glaucoma is complex, multifaceted, and not fully understood. [1][2][3] It has been hypothesized that elevated intraocular pressure (IOP) and impaired retinal blood flow are initiating factors in glaucomatous optic nerve damage. 3 The onset of retinal neurodegeneration in glaucoma may also be influenced by cumulative oxidative stress in conjunction with chronic mechanical and vascular stress.…”

Section: Introductionmentioning

confidence: 99%

Association between Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists Exposure and Intraocular Pressure Change

Hallaj,

Halfpenny,

Chuter

et al. 2024

Preprint

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Objective This study aims to provide data on the effects of glucagon-like peptide 1 receptor (GLP-1R) agonists on intraocular pressure (IOP). Design Retrospective cohort study. Subjects, Participants, and/or Controls 1247 glaucoma surgery and treatment-naive eyes of 626 patients who were initiated on GLP-1R agonists compared to 1083 glaucoma surgery and treatment-naive eyes of 547 patients who were initiated on other oral antidiabetics. Methods, Intervention, or Testing The University of California Health Data Warehouse was queried for patients exposed to GLP-1R agonists or other oral antidiabetics. Index date was defined as the date of first exposure to the medication. Eyes with at least one pre-exposure and one post-exposure tonometry record within 365 days of the index date were included in the analysis. Clinical and laboratory data elements were extracted from the database. Eyes were censored from the analysis upon exposure to glaucoma hypotensive medication or glaucoma surgery. ∆IOP was analyzed using a paired t-test. Regression analysis was conducted using generalized estimating equations (GEE) accounting for inter-eye correlation. Sensitivity analyses were performed to assess the robustness of the findings. Main Outcome Measures Primary outcome measure was ∆IOP after exposure to the medication. Results The median age of all included subjects was 66.2 years [IQR=18.3]; 607 (51.7%) were female, and 667 (56.9%) were Caucasian. Median pre-exposure IOP, HbA1c, and BMI were 15.2 mmHg [IQR=3.8], 7.5 [IQR=2.4], and 29.8 [IQR=9.4], respectively. 776 individuals (66.1%) had diabetes, with the median number of active oral antidiabetics being 1.0 [IQR=1.0], and 441 (37.5%) being insulin users. Several pre-exposure characteristics significantly differed between the GLP-1R agonist and the control group. The mean ∆IOP was -0.4 mmHg (SD=2.8) (paired t-test p<0.001) and -0.2 mmHg (SD=3.3) (paired t-test p = 0.297) in the GLP-1R agonist and other antidiabetics groups, respectively. Pre-exposure IOP was the only independent predictor of ΔIOP in multivariable GEE. Sensitivity analyses yielded similar results. Conclusions Although GLP-1R agonists were significantly associated with a decrease in IOP in the paired analysis, they were not associated with ΔIOP in multivariable GEE. Moreover, the difference between the ΔIOP in the two groups was small. Future prospective studies following a standardized dose and delivery method may provide further insights.

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Section: Introductionmentioning

confidence: 99%

Association between Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists Exposure and Intraocular Pressure Change

Hallaj,

Halfpenny,

Chuter

et al. 2024

Preprint

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“…Interestingly, multiple studies have shown that electrical stimulation is also known to be effective in protecting a degenerating retina. A variety of approaches, such as subretinal-, transcorneal- or whole eye electrical stimulation, showed a partial recovery of visual function [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Electric Field Stimulation in Blue Light Stressed 661W Cells

Bola

Subramanian

Calzia

et al. 2023

IJMS

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Though electrical stimulation is used as a therapeutic approach to treat retinal and spinal injuries, many protective mechanisms at cellular level have not been elucidated. We performed a detailed analysis of cellular events in blue light (Li) stressed 661W cells, which were subjected to direct current electric field (EF) stimulation. Our findings revealed that EF stimulation induced protective effects in 661W cells from Li-induced stress by multiple defense mechanisms, such as increase in mitochondrial activity, gain in mitochondrial potential, increase in superoxide levels, and the activation of unfolded protein response (UPR) pathways, all leading to an enhanced cell viability and decreased DNA damage. Here, our genetic screen results revealed the UPR pathway to be a promising target to ameliorate Li-induced stress by EF stimulation. Thus, our study is important for a knowledgeable transfer of EF stimulation into clinical application.

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“…Photoreceptor dystrophies and degenerative diseases of the retina are major causes of blindness worldwide, ranging till 5-14% in age-related macular degeneration [1]. In recent studies, electric fields (EF, e.g., via transcorneal electric stimulation -TCES) have been successfully applied to treat such retinal diseases [2][3][4][5][6] as well of degenerative diseases of the optic nerve [7,8].…”

Section: Introductionmentioning

confidence: 99%

Effect of Direct Current Electric Fields on Cone Like Retinal Photoreceptor Cells

Guerra-Hühne¹,

Bola²,

Calzia³

et al. 2022

Front. Biosci. (Landmark Ed)

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Introduction: Studies show that electric fields are used as therapy during nerve and tissue injuries along with trans-retinal stimulation. However, cellular and molecular changes induced by such treatments remain largely unknown especially in retinal photoreceptor cells.In vitro studies show that direct current electric fields (dcEF) were known to influence cell division, polarity, shape, and motility. Here we could characterize for the first time the reactions of 661W, a retinal cone photoreceptor especially regarding organelle polarization, membrane polarization of mitochondria, O2 consumption, ATP/ADP ratio and gene expression. Methods: The 661W cells were stimulated with a constant dcEF of field strength 5 V/cm during 30 min or 5 h depending on the parameters studied. Results: In response to dcEF, the cells aligned perpendicular to the field by forming a leading edge with extended membrane protrusions towards the cathode. Using immunofluorescence and live cell imaging, we show that the cell membrane depolarized at the cathodal side. The microtubules spread into the direction of migration. Also, the microtubule organization center re-oriented into this direction. Concomitantly with the microtubules, actin filaments reorganized in an asymmetrical fashion mainly at the cathodal side. The Golgi apparatus, which is involved in many steps of actin synthesis, moved to the cathodal side. In the last 2 h of the 5 h experiment, microtubules positioned themselves at the rear (anodal side), like the nucleus. The averaged displacement of the whole cells under dcEF was 155% of control for 3 V/cm and 235% for 5 V/cm. The average speed increased by 142% and 243% respectively. Inside the cells mitochondria moved to the cathodal side, where the energy consuming producing processes take place. In this line, we measured an increase in ATP production and O2 consumption. Mitochondrial calcium was found more on the anodal side, at the site of the nucleus with its calcium delivering endoplasmic reticulum. In addition, oxymetry studies reveal an increased ATP synthesis by 115.2% and oxygen consumption by 113.3% 3 h after dcEF stimulation. An analysis of differentially expressed genes by RNA sequencing revealed an upregulation of genes involved in cellular movement, cell to cell and intracellular signaling, molecular transport, assembly and organization. Conclusions: The mechanisms found can enhance our understanding regarding the beneficial effects of EF treatment in retinal diseases.

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Cell-Based Neuroprotection of Retinal Ganglion Cells in Animal Models of Optic Neuropathies

Cited by 3 publications

References 185 publications

Association between Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists Exposure and Intraocular Pressure Change

Association between Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists Exposure and Intraocular Pressure Change

Analysis of Electric Field Stimulation in Blue Light Stressed 661W Cells

Effect of Direct Current Electric Fields on Cone Like Retinal Photoreceptor Cells

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