ArticleJournal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics2017
A Novel Neuroprotective Small Molecule for Glial Cell Derived Neurotrophic Factor Induction and Photoreceptor Rescue.
Article in Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Proteomic profiling reveals treatment-dependent inflammatory signatures and identifies biomarkers of refractory age-related macular degeneration.Frontiers in pharmacology · 2026Article
- AI-organoid integrated systems for biomedical studies and applications.Bioengineering & translational medicine · 2024Review
- Human Neural Progenitors Expressing GDNF Enhance Retinal Protection in a Rodent Model of Retinal Degeneration.Stem cells translational medicine · 2023Article
- Potential therapeutic strategies for photoreceptor degeneration: the path to restore vision.Journal of translational medicine · 2022Review
- Early onset monocular hydroxychloroquine maculopathy in a systemic lupus erythematosus patient with history of central retinal artery occlusion: a case report.BMC ophthalmology · 2022Article
- Glial cell line-derived neurotrophic factor (GDNF) in patients with primary open-angle glaucoma and age-related cataract.Molecular vision · 2022Article
- Co-delivery of glial cell-derived neurotrophic factor (GDNF) and tauroursodeoxycholic acid (TUDCA) from PLGA microspheres: potential combination therapy for retinal diseases.Drug delivery and translational research · 2021Article
- Small-molecule agonists of the RET receptor tyrosine kinase activate biased trophic signals that are influenced by the presence of GFRa1 co-receptors.The Journal of biological chemistry · 2020Article
- Convolutional Neural Networks Can Predict Retinal Differentiation in Retinal Organoids.Frontiers in cellular neuroscience · 2020Article
- Article
- Regenerative medicine in the retina: from stem cells to cell replacement therapy.Therapeutic advances in ophthalmologyReview
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeDegenerative diseases of the retina, such as retinitis pigmentosa and age-related macular degeneration, are characterized by the irreversible loss of photoreceptors. Several growth factors, including glial cell derived neurotrophic factor (GDNF), have been shown to rescue retinal neurons. An alternative strategy to direct GDNF administration is its induction in host retina by small molecules. Here we studied the ability of a novel small molecule GSK812 to induce GDNF in vitro/in vivo and rescue photoreceptors.
methodsGDNF induction in vitro was assessed in human ARPE-19, human retinal progenitor cells (RPCs) and mouse pluripotent cell-derived eyecups. For time course pharmacokinetic and GDNF induction studies in C57Bl/6 mice, GSK812 sustained release formulation was injected intravitreally. The same delivery approach was used in the rhodopsin knockout mice and Royal College of Surgeon (RCS) rats to assess long-term GDNF induction and photoreceptor rescue.
resultsThe suspension provided sustained GSK812 delivery with 28 μg of drug remaining in the eye 2 weeks after a single injection. GSK812 suspension injection in C57Bl/6 mice resulted in significant upregulation of GDNF mRNA (>1.8-fold) and protein levels (>2.8-fold). Importantly, GSK812 treatment resulted in outer nuclear layer preservation in rho
conclusionsGSK812 is a potent neuroprotectant that can induce GDNF in normal and diseased retina. This induction results in photoreceptor rescue in 2 models of retinal degeneration.
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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.