scholarly journals Neuroprotective Role of GLP-1 Analog for Retinal Ganglion Cells via PINK1/Parkin-Mediated Mitophagy in Diabetic Retinopathy

2021 ◽  
Vol 11 ◽  
Author(s):  
Huan-ran Zhou ◽  
Xue-fei Ma ◽  
Wen-jian Lin ◽  
Ming Hao ◽  
Xin-yang Yu ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Ganglion Cells ◽  
Neuroprotective Effect ◽  
Diabetic Rat ◽  
Retinal Ganglion

GLP-1 analogs have been widely used to treat patients with type 2 diabetes in recent years and studies have found that GLP-1 analogs have multiple organ benefits. However, the role of GLP-1 analogs in diabetic retinopathy (DR), a common complication of diabetes mellitus (DM), remains controversial. Retinal ganglion cells (RGCs) are the only afferent neurons responsible for transmitting visual information to the visual center and are vulnerable in the early stage of DR. Protection of RGC is vital for visual function. The incretin glucagon-like peptide-1 (GLP-1), which is secreted by L-cells after food ingestion, could lower blood glucose level through stimulating the release of insulin. In the present study, we evaluated the effects of GLP-1 analog on RGCs both in vitro and in vivo. We established diabetic rat models in vivo and applied an RGC-5 cell line in vitro. The results showed that in high glucose conditions, GLP-1 analog alleviated the damage of RGCs. In addition, GLP-1 analog prevented mitophagy through the PINK1/Parkin pathway. Here we demonstrated the neuroprotective effect of GLP-1 analog, which may be beneficial for retinal function, and we further elucidated a novel mechanism in GLP-1 analog-regulated protection of the retina. These findings may expand the multi-organ benefits of GLP-1 analogs and provide new insights for the prevention of DR.

scholarly journals MicroRNA-93/STAT3 signalling pathway mediates retinal microglial activation and protects retinal ganglion cells in an acute ocular hypertension model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yayi Wang ◽  
Shida Chen ◽  
Jiawei Wang ◽  
Yaoming Liu ◽  
Yang Chen ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Retinal Ganglion Cells ◽  
Microglial Activation ◽  
Ganglion Cells ◽  
Neuroprotective Effect ◽  
Retinal Ganglion ◽  
Neuroprotective Therapy ◽  
Retinal Microglia

AbstractGlaucoma is a common neurodegenerative disease and a leading cause of irreversible blindness worldwide. Retinal microglia-mediated neuroinflammation is involved in the process of optic nerve damage, but the mechanisms driving this microglial activation remain mostly elusive. Previous investigations reported that microRNAs are associated with the retinal microglial reaction and neural apoptosis. In the present study, we found that microRNA-93-5p (miR-93) played a key role in the reaction of retinal microglial cells in vivo and in vitro. The miR-93 level was significantly reduced in the retinae of rat acute ocular hypertension (AOH) models, which were accompanied by retinal microglial activation, overproduction of inflammatory cytokines, and subsequent retinal ganglion cells (RGCs) death, versus the retinae of controls. The induction of miR-93 overexpression significantly reduced microglial proliferation, migration and cytokine release, inhibited the expression of the target gene signal transducer and activator of transcription 3 (STAT3) and p-STAT3, and was associated with a reduced loss of RGCs. Treatment with a STAT3 inhibitor also decreased retinal microglial activation after AOH injury. Taken together, these results suggest that the miR-93/STAT3 pathway is directly related to the downregulation of retinal microglia-mediated neuro-inflammation and showed a neuroprotective effect. Regulating microglial activation through miR-93 may serve as a target for neuroprotective therapy in pathological ocular hypertension.

scholarly journals A method for single-neuron chronic recording from the retina in awake mice

Science ◽  
2018 ◽  
Vol 360 (6396) ◽  
pp. 1447-1451 ◽  
Author(s):  
Guosong Hong ◽  
Tian-Ming Fu ◽  
Mu Qiao ◽  
Robert D. Viveros ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Single Neuron ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Neural Circuitry ◽  
Retinal Ganglion ◽  
Chronic Recording ◽  
The Brain

The retina, which processes visual information and sends it to the brain, is an excellent model for studying neural circuitry. It has been probed extensively ex vivo but has been refractory to chronic in vivo electrophysiology. We report a nonsurgical method to achieve chronically stable in vivo recordings from single retinal ganglion cells (RGCs) in awake mice. We developed a noncoaxial intravitreal injection scheme in which injected mesh electronics unrolls inside the eye and conformally coats the highly curved retina without compromising normal eye functions. The method allows 16-channel recordings from multiple types of RGCs with stable responses to visual stimuli for at least 2 weeks, and reveals circadian rhythms in RGC responses over multiple day/night cycles.

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

2009 ◽  
Vol 247 (10) ◽  
pp. 1353-1360 ◽  
Author(s):  
Akiyasu Kanamori ◽  
Maiko Naka ◽  
Masahide Fukuda ◽  
Makoto Nakamura ◽  
Akira Negi
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion

miR-223 induces retinal ganglion cells apoptosis and inflammation via decreasing HSP-70 in vitro and in vivo

2020 ◽  
Vol 104 ◽  
pp. 101747 ◽  
Author(s):  
Yun Ou-Yang ◽  
Zheng-Li Liu ◽  
Chun-Long Xu ◽  
Jia-Liang Wu ◽  
Jun Peng ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Hsp 70 ◽  
Apoptosis And Inflammation

scholarly journals Brazilian Green Propolis Protects against Retinal Damage In Vitro and In Vivo

2006 ◽  
Vol 3 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Yuta Inokuchi ◽  
Masamitsu Shimazawa ◽  
Yoshimi Nakajima ◽  
Shinsuke Suemori ◽  
Satoshi Mishima ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Water Soluble ◽  
Retinal Damage ◽  
Retinal Ganglion ◽  
Neuroprotective Effects ◽  
Brazilian Green Propolis

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.

Neuroprotective effect of alpha-lipoic acid on hydrostatic pressure-induced damage of retinal ganglion cells in vitro

2012 ◽  
Vol 526 (1) ◽  
pp. 24-28 ◽  
Author(s):  
Bing Liu ◽  
Xiaohua Ma ◽  
Dadong Guo ◽  
Yuanyuan Guo ◽  
Ninghong Chen ◽  
...  
Keyword(s):  
Hydrostatic Pressure ◽  
Retinal Ganglion Cells ◽  
Lipoic Acid ◽  
Ganglion Cells ◽  
Neuroprotective Effect ◽  
Retinal Ganglion ◽  
Alpha Lipoic Acid

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

2009 ◽  
Vol 88 (3) ◽  
pp. 535-541 ◽  
Author(s):  
Akiyasu Kanamori ◽  
Maiko Naka ◽  
Masahide Fukuda ◽  
Makoto Nakamura ◽  
Akira Negi
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion

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

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
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.

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

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.

Sign in / Sign up

Export Citation Format

Share Document