ArticleCell death & disease2020
Rac1 conditional deletion attenuates retinal ganglion cell apoptosis by accelerating autophagic flux in a mouse model of chronic ocular hypertension.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Stage- and compartment-specific remodeling of autophagy and selective mitophagy in glaucoma: from aqueous outflow dysfunction to retinal ganglion cell neurodegeneration.Frontiers in cell and developmental biology · 2026Review
- Tumor Necrosis Factor Alpha-Mediated Interaction Between Microglia and Müller Cells Exacerbates Retinal Ganglion Cell Damage in Experimental Glaucoma.Neuroscience bulletin · 2026Article
- A High-Fidelity RNA-Targeting Cas13X Downregulates Connexin43 in Macroglia: A Novel Neuroprotective Strategy for Glaucoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Leveraging AAV1-Rac1T17N to prevent experimental proliferative vitreoretinopathy.Journal of translational medicine · 2025Article
- Mettl3-Mediated N6-Methyladenosine Modification Mitigates Ganglion Cell Loss and Retinal Dysfunction in Retinal Ischemia-Reperfusion Injury by Inhibiting FoxO1-Mediated Autophagy.Investigative ophthalmology & visual science · 2025Article
- The role of microglia in glaucoma - trigger and potential target.Frontiers in immunology · 2025Review
- Selective deletion of zinc transporter 3 in amacrine cells promotes retinal ganglion cell survival and optic nerve regeneration after injury.Neural regeneration research · 2023Article
- Autophagy deficiency protects against ocular hypertension and neurodegeneration in experimental and spontanous glaucoma mouse models.Cell death & disease · 2023Article
- GGT1 Suppresses the Development of Ferroptosis and Autophagy in Mouse Retinal Ganglion Cell Through Targeting GCLC.Eye and brain · 2023Article
- P2X7/P2X4 Receptors Mediate Proliferation and Migration of Retinal Microglia in Experimental Glaucoma in Mice.Neuroscience bulletin · 2022Article
- mTOR Signalling Pathway: A Potential Therapeutic Target for Ocular Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2022Review
- Antiviral Effects of ABMA and DABMA against Influenza Virus In Vitro and In Vivo via Regulating the Endolysosomal Pathway and Autophagy.International journal of molecular sciences · 2022Article
- Loss of JNK-Associated Leucine Zipper Protein Promotes Peritoneal Dialysis-Related Peritoneal Fibrosis.Kidney diseases (Basel, Switzerland) · 2022Article
- The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases.Cell & bioscience · 2022Review
- Rapamycin and Resveratrol Modulate the Gliotic and Pro-Angiogenic Response in Müller Glial Cells Under Hypoxia.Frontiers in cell and developmental biology · 2022Article
- Recruitment of LC3 byFrontiers in cellular and infection microbiology · 2022Article
- Autophagy in glaucoma pathogenesis: Therapeutic potential and future perspectives.Frontiers in cell and developmental biology · 2022Review
- Interplay between Müller cells and microglia aggravates retinal inflammatory response in experimental glaucoma.Journal of neuroinflammation · 2021Article
- Ligustrazine protects against chronic hypertensive glaucoma in rats by inhibiting autophagy via the PI3K-Akt/mTOR pathway.Molecular vision · 2021Article
- Berberine ameliorates vascular dysfunction by a global modulation of lncRNA and mRNA expression profiles in hypertensive mouse aortae.PloS one · 2021Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy has a fundamental role in maintaining cell homeostasis. Although autophagy has been implicated in glaucomatous pathology, how it regulates retinal ganglion cell (RGC) injury is largely unknown. In the present work, we found that biphasic autophagy in RGCs occurred in a mouse model of chronic ocular hypertension (COH), accompanied by activation of Rac1, a member of the Rho family. Rac1 conditional knockout (Rac1 cKO) in RGCs attenuated RGC apoptosis, in addition to blocking the increase in the number of autophagosomes and the expression of autophagy-related proteins (Beclin1, LC3-II/I, and p62) in COH retinas. Electron micrograph and double immunostaining of LAMP1 and LC3B showed that Rac1 cKO accelerated autolysosome fusion in RGC axons of COH mice. Inhibiting the first autophagic peak with 3-methyladenine or Atg13 siRNA reduced RGC apoptosis, whereas inhibiting the second autophagic peak with 3-MA or blocking autophagic flux by chloroquine increased RGC apoptosis. Furthermore, Rac1 cKO reduced the number of autophagosomes and apoptotic RGCs induced by rapamycin injected intravitreally, which suggests that Rac1 negatively regulates mTOR activity. Moreover, Rac1 deletion decreased Bak expression and did not interfere with the interaction of Beclin1 and Bcl-2 or Bak in COH retinas. In conclusion, autophagy promotes RGC apoptosis in the early stages of glaucoma and results in autophagic cell death in later stages. Rac1 deletion alleviates RGC damage by regulating the cross talk between autophagy and apoptosis through mTOR/Beclin1-Bak. Interfering with the Rac1/mTOR signaling pathway may provide a new strategy for treating glaucoma.
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