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• W2610247597 abstract "Purpose: Degenerative 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. Methods: GDNF 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. Results: The 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−/− mice with a 2-fold difference in photoreceptor number. In the RCS rat, the GSK812 injection provided long-term rescue of photoreceptors and outer segments, accompanied by function preservation as well. Conclusions: GSK812 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." @default.
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• W2610247597 date "2017-06-01" @default.
• W2610247597 modified "2023-10-16" @default.
• W2610247597 title "A Novel Neuroprotective Small Molecule for Glial Cell Derived Neurotrophic Factor Induction and Photoreceptor Rescue" @default.
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• W2610247597 doi "https://doi.org/10.1089/jop.2016.0121" @default.
• W2610247597 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5911694" @default.
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