Tafluprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo

Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory) effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retinain vitroand/orin vivo.In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2) exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin–reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus) by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation), as also did trolox (water-soluble vitamin E). In micein vivo, propolis (100 mg kg−1; intraperitoneally administered four times) reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer) induced by intravitrealin vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage bothin vitroandin vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects.

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Latanoprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo

Experimental Eye Research ◽

10.1016/j.exer.2008.11.012 ◽

2009 ◽

Vol 88 (3) ◽

pp. 535-541 ◽

Cited By ~ 26

Author(s):

Akiyasu Kanamori ◽

Maiko Naka ◽

Masahide Fukuda ◽

Makoto Nakamura ◽

Akira Negi

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Retinal Ganglion

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Dexamethasone Provides Effective Immunosuppression for Improved Survival of Retinal Organoids after Epiretinal Transplantation

Stem Cells International ◽

10.1155/2019/7148032 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 2

Author(s):

Bikun Xian ◽

Ziming Luo ◽

Kaijing Li ◽

Kang Li ◽

Mingjun Tang ◽

...

Keyword(s):

Rhesus Monkey ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Immunosuppressive Treatment ◽

Retinal Ganglion ◽

Chain Reaction ◽

Immunological Rejection ◽

Polymerase Chain

We investigated the efficacy of the immunosuppressants rapamycin (RAP) and dexamethasone (DEX) in improving the survival of retinal organoids after epiretinal transplantation. We first compared the immunosuppressive abilities of DEX and RAP in activated microglia in an in vitro setting. Following this, we used immunofluorescence, real-time polymerase chain reaction, and flow cytometry to investigate the effects of DEX and RAP on cells in the retinal organoids. Retinal organoids were then seeded onto poly(lactic-co-glycolic) acid (PLGA) scaffolds and implanted into rhesus monkey eyes (including a healthy individual and three monkeys with chronic ocular hypertension (OHT) induction) and subjected to different post-operative immunosuppressant treatments; 8 weeks after the experiment, histological examinations were carried out to assess the success of the different treatments. Our in vitro experiments indicated that both DEX and RAP treatments were equally effective in suppressing microglial activity. Although both immunosuppressants altered the morphologies of cells in the retinal organoids and caused a slight decrease in the differentiation of cells into retinal ganglion cells, the organoid cells retained their capacity to grow and differentiate into retinal tissues. Our in vivo experiments indicate that the retinal organoid can survive and differentiate into retinal tissues in a healthy rhesus monkey eye without immunosuppressive treatment. However, the survival and differentiation of these organoids in OHT eyes was successful only with the DEX treatment. RAP treatment was ineffective in preventing immunological rejection, and the retinal organoid failed to survive until the end of 8 weeks. DEX is likely a promising immunosuppressant to enhance the survival of epiretinal implants.

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Pharmacological Inhibition of PTEN, using BpV (Phen), Promotes Survival of Retinal Ganglion Cells In Vitro and In Vivo

10.22215/etd/2019-13794 ◽

2019 ◽

Author(s):

Dennis Chan

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Retinal Ganglion ◽

Pharmacological Inhibition

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Dual SMAD inhibition and Wnt inhibition enable efficient and reproducible differentiations of induced pluripotent stem cells into retinal ganglion cells

10.1101/682666 ◽

2019 ◽

Author(s):

Venkata R. M. Chavali ◽

Naqi Haider ◽

Sonika Rathi ◽

Vrathasha Vrathasha ◽

Teja Alapati ◽

...

Keyword(s):

Stem Cells ◽

Optic Nerve ◽

Visual Field ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Visual Field Loss ◽

Nerve Degeneration ◽

Retinal Ganglion

AbstractGlaucoma is a group of progressive optic neuropathies that share common biological and clinical characteristics including irreversible changes to the optic nerve and visual field loss caused by death of retinal ganglion cells (RGCs). The loss of RGCs manifests as characteristic cupping or optic nerve degeneration, resulting in visual field loss in patients with Glaucoma. Published studies on in vitro RGC differentiation from stem cells utilized classical RGC signaling pathways mimicking retinal development in vivo. Although many strategies allowed for the generation of RGCs, increased variability between experiments and lower yield hampered the cross comparison between individual lines and between experiments. To address this critical need, we developed a reproducible chemically defined in vitro methodology for generating retinal progenitor cell (RPC) populations from iPSCs, that are efficiently directed towards RGC lineage. Using this method, we reproducibly differentiated iPSCs into RGCs with greater than 80% purity, without any genetic modifications. We used small molecules and peptide modulators to inhibit BMP, TGF-β (SMAD), and canonical Wnt pathways that reduced variability between iPSC lines and yielded functional and mature iPSC-RGCs. Using CD90.2 antibody and Magnetic Activated Cell Sorter (MACS) technique, we successfully purified Thy-1 positive RGCs with nearly 95% purity.

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Long-term in vivo and in vitro AAV-2-mediated RNA interference in rat retinal ganglion cells and cultured primary neurons

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2004.11.029 ◽

2005 ◽

Vol 326 (2) ◽

pp. 307-312 ◽

Cited By ~ 34

Author(s):

Uwe Michel ◽

Ibrahim Malik ◽

Sandra Ebert ◽

Mathias Bähr ◽

Sebastian Kügler

Keyword(s):

Rna Interference ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Primary Neurons ◽

Retinal Ganglion

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P3HT:Bebq2-Based Photovoltaic Device Enhances Differentiation of hiPSC-Derived Retinal Ganglion Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20112661 ◽

2019 ◽

Vol 20 (11) ◽

pp. 2661

Author(s):

Chih-Chen Hsu ◽

Yi-Ying Lin ◽

Tien-Chun Yang ◽

Aliaksandr A. Yarmishyn ◽

Tzu-Wei Lin ◽

...

Keyword(s):

Cell Fate ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Bulk Heterojunction ◽

Visible Spectrum ◽

Photovoltaic Device ◽

Visual Signals ◽

Retinal Ganglion

Electric field stimulation is known to affect various cellular processes, including cell fate specification and differentiation, particularly towards neuronal lineages. This makes it a promising therapeutic strategy to stimulate regeneration of neuronal tissues. Retinal ganglion cells (RGCs) is a type of neural cells of the retina responsible for transduction of visual signals from the retina to the brain cortex, and is often degenerated in various blindness-causing retinal diseases. The organic photovoltaic materials such as poly-3-hexylthiophene (P3HT) can generate electric current upon illumination with light of the visible spectrum, and possesses several advantageous properties, including light weight, flexibility and high biocompatibility, which makes them a highly promising tool for electric stimulation of cells in vitro and in vivo. In this study, we tested the ability to generate photocurrent by several formulations of blend (bulk heterojunction) of P3HT (which is electron donor material) with several electron acceptor materials, including Alq3 and bis(10-hydroxybenzo[h]quinolinato)beryllium (Bebq2). We found that the photovoltaic device based on bulk heterojunction of P3HT with Bebq2 could generate photocurrent when illuminated by both green laser and visible spectrum light. We tested the growth and differentiation capacity of human induced pluripotent stem cells (hiPSC)-derived RGCs when grown in interface with such photostimulated device, and found that they were significantly increased. The application of P3HT:Bebq2-formulation of photovoltaic device has a great potential for developments in retinal transplantation, nerve repair and tissue engineering approaches of treatment of retinal degeneration.

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The mito-QC Reporter for Quantitative Mitophagy Assessment in Primary Retinal Ganglion Cells and Experimental Glaucoma Models

International Journal of Molecular Sciences ◽

10.3390/ijms21051882 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1882

Author(s):

Ines Rosignol ◽

Beatriz Villarejo-Zori ◽

Petra Teresak ◽

Elena Sierra-Filardi ◽

Xandra Pereiro ◽

...

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Ex Vivo ◽

Iron Chelator ◽

Stress Factors ◽

Retinal Ganglion ◽

Nerve Crush ◽

Experimental Glaucoma

Mitochondrial damage plays a prominent role in glaucoma. The only way cells can degrade whole mitochondria is via autophagy, in a process called mitophagy. Thus, studying mitophagy in the context of glaucoma is essential to understand the disease. Up to date limited tools are available for analyzing mitophagy in vivo. We have taken advantage of the mito-QC reporter, a recently generated mouse model that allows an accurate mitophagy assessment to fill this gap. We used primary RGCs and retinal explants derived from mito-QC mice to quantify mitophagy activation in vitro and ex vivo. We also analyzed mitophagy in retinal ganglion cells (RGCs), in vivo, using different mitophagy inducers, as well as after optic nerve crush (ONC) in mice, a commonly used surgical procedure to model glaucoma. Using mito-QC reporter we quantified mitophagy induced by several known inducers in primary RGCs in vitro, ex vivo and in vivo. We also found that RGCs were rescued from some glaucoma relevant stress factors by incubation with the iron chelator deferiprone (DFP). Thus, the mito-QC reporter-based model is a valuable tool for accurately analyzing mitophagy in the context of glaucoma.

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