ArticleInvestigative ophthalmology & visual science2012
Silencing of Fem1cR3 gene expression in the DBA/2J mouse precedes retinal ganglion cell death and is associated with histone deacetylase activity.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 58 citations in OpenAlex.
- Transcending genome-wide association studies to create useful multi-omic views of glaucoma.Progress in retinal and eye research · 2026Review
- Cytokine Gene Polymorphisms in Primary Glaucoma: Insights into Inflammatory Pathways and Future Directions.Molecular neurobiology · 2026Review
- Epigenetics of glaucoma in the trabecular meshwork.Clinical epigenetics · 2025Review
- Intravitreal AAV2 gene delivery to feline retinal ganglion cells.Vision research · 2025Article
- Preservation of Murine Whole Eyes With Supplemented UW Cold Storage Solution: Anatomical Considerations.Translational vision science & technology · 2024Article
- Epigenetics in Glaucoma.Medicina (Kaunas, Lithuania) · 2024Review
- Roles of Histone Acetyltransferases and Deacetylases in the Retinal Development and Diseases.Molecular neurobiology · 2023Review
- Molecular regulation of neuroinflammation in glaucoma: Current knowledge and the ongoing search for new treatment targets.Progress in retinal and eye research · 2022Review
- Increased Susceptibility and Intrinsic Apoptotic Signaling in Neurons by Induced HDAC3 Expression.Investigative ophthalmology & visual science · 2021Article
- Review
- Changes in Class I and IIb HDACs by δ-Opioid in Chronic Rat Glaucoma Model.Investigative ophthalmology & visual science · 2020Article
- Targeting HDAC3 in the DBA/2J spontaneous mouse model of glaucoma.Experimental eye research · 2020Article
- BAX-Depleted Retinal Ganglion Cells Survive and Become Quiescent Following Optic Nerve Damage.Molecular neurobiology · 2020Article
- A broad perspective on the molecular regulation of retinal ganglion cell degeneration in glaucoma.Progress in brain research · 2020Review
- Histone Deacetylases Contribute to Excitotoxicity-Triggered Degeneration of Retinal Ganglion Cells In Vivo.Molecular neurobiology · 2019Article
- Targeting HDAC3 Activity with RGFP966 Protects Against Retinal Ganglion Cell Nuclear Atrophy and Apoptosis After Optic Nerve Injury.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2018Article
- Novel Therapeutics in Glaucoma Management.Current neuropharmacology · 2018Review
- Ezh2 does not mediate retinal ganglion cell homeostasis or their susceptibility to injury.PloS one · 2018Article
- Curcumin Modulates DNA Methyltransferase Functions in a Cellular Model of Diabetic Retinopathy.Oxidative medicine and cellular longevity · 2018Article
- AAV2-Mediated Transduction of the Mouse Retina After Optic Nerve Injury.Investigative ophthalmology & visual science · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
purposeDownregulation of normal gene expression in dying retinal ganglion cells has been documented in both acute and chronic models of optic nerve disease. The authors examined the mechanism and timing of this phenomenon in DBA/2J mice, using genetically modified substrains of this inbred line.
methodsDBA/2J mice, doubly congenic for the Bax mutant allele and the ganglion cell reporter gene Fem1c(Rosa3) (R3), were evaluated to elucidate the timing of loss of normal gene expression during the apoptotic process. The localization of histone deacetylase 3 (HDAC3) and nuclear histone H4 acetylation were examined by immunofluorescence in dying cells. The role of HDACs in gene silencing during glaucoma was interrogated using the global HDAC inhibitor trichostatin A (TSA).
resultsSilencing of the R3 allele occurred in Bax(-/-) ganglion cells, indicating that this process preceded the committed step of the intrinsic apoptotic pathway. Weekly TSA treatment, between the ages of 6 and 10 months, was able to attenuate the loss of R3 expression in the retina, but had no effect on optic nerve degeneration. Dying cells in aging DBA/2J mice exhibited nuclear localization of HDAC3 and a decrease in the level of H4 acetylation.
conclusionsRetinal ganglion cells exhibit a loss of normal gene expression as an early (pre-BAX involvement) part of their apoptotic program during glaucomatous degeneration. This process can be ameliorated, but not completely blocked, using HDAC inhibitors. Epigenetic changes to active chromatin, such as deacetylation, may be mediated by HDAC3 in dying neurons.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.