ArticleNeurobiology of disease2014
Combinatorial targeting of early pathways profoundly inhibits neurodegeneration in a mouse model of glaucoma.
Article in Neurobiology of disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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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
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Who cites it
69 citing papers in PubMed, 114 citations in OpenAlex.
- Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Dual role of microglia in glaucoma: Regulation of neuroinflammation and neuroregeneration.Neural regeneration research · 2026Article
- Intraocular pressure induced blood retinal barrier compromise in mouse models and human glaucoma.Nature communications · 2026Article
- IL1A enhances TNF-induced retinal ganglion cell death.Frontiers in aging neuroscience · 2026Article
- Rodent Models of Glaucoma: How Mice and Rats Can Help Human Vision Move Out of the Woods and Into the Light.Cells · 2025Review
- Associations Between Cerebral Perfusion Pressure, Hemodynamic Parameters, and Cognitive Test Values in Normal-Tension Glaucoma Patients, Alzheimer's Disease Patients, and Healthy Controls.Medicina (Kaunas, Lithuania) · 2025Article
- The Identification of New Pharmacological Targets for the Treatment of Glaucoma: A Network Pharmacology Approach.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Lycium barbarum glycopeptide promotes neuroprotection in ET-1 mediated retinal ganglion cell degeneration.Journal of translational medicine · 2024Article
- The Role of Complement Dysregulation in Glaucoma.International journal of molecular sciences · 2024Review
- Nicotinamide Prevents Retinal Vascular Dropout in a Rat Model of Ocular Hypertension and Supports Ocular Blood Supply in Glaucoma Patients.Investigative ophthalmology & visual science · 2023Article
- Immunomodulatory and Antioxidant Drugs in Glaucoma Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Recently Approved Drugs for Lowering and Controlling Intraocular Pressure to Reduce Vision Loss in Ocular Hypertensive and Glaucoma Patients.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The endothelin receptor antagonist macitentan ameliorates endothelin-mediated vasoconstriction and promotes the survival of retinal ganglion cells in rats.Frontiers in ophthalmology · 2023Article
- Involvement of endothelins in neuroprotection of valosin-containing protein modulators against retinal ganglion cell damage.Scientific reports · 2022Article
- The characteristics of fundus microvascular alterations in the course of glaucoma: a narrative review.Annals of translational medicine · 2022Review
- Vascular derived endothelin receptor A controls endothelin-induced retinal ganglion cell death.Cell death discovery · 2022Article
- Myeloid cells in retinal and brain degeneration.The FEBS journal · 2022Review
- Solving neurodegeneration: common mechanisms and strategies for new treatments.Molecular neurodegeneration · 2022Review
- Transcriptional control of retinal ganglion cell death after axonal injury.Cell death & disease · 2022Article
- Molecular regulation of neuroinflammation in glaucoma: Current knowledge and the ongoing search for new treatment targets.Progress in retinal and eye research · 2022Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The endothelin system is implicated in various human and animal glaucomas. Targeting the endothelin system has great promise as a treatment for human glaucoma, but the cell types involved and the exact mechanisms of action are not clearly elucidated. Here, we report a detailed characterization of the endothelin system in specific cell types of the optic nerve head (ONH) during glaucoma in DBA/2J mice. First, we show that key components of the endothelin system are expressed in multiple cell types. We discover that endothelin 2 (EDN2) is expressed in astrocytes as well as microglia/monocytes in the ONH. The endothelin receptor type A (Ednra) is expressed in vascular endothelial cells, while the endothelin receptor type B (Ednrb) receptor is expressed in ONH astrocytes. Second, we show that Macitentan treatment protects from glaucoma. Macitentan is a novel, orally administered, dual endothelin receptor antagonist with greater affinity, efficacy and safety than previous antagonists. Finally, we test the combinatorial effect of targeting both the endothelin and complement systems as a treatment for glaucoma. Similar to endothelin, the complement system is implicated in a variety of human and animal glaucomas, and has great promise as a treatment target. We discovered that combined targeting of the endothelin (Bosentan) and complement (C1qa mutation) systems is profoundly protective. Remarkably, 80% of DBA/2J eyes subjected to this combined inhibition developed no detectable glaucoma. This opens an exciting new avenue for neuroprotection in glaucoma.
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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.