Eye / Vision
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/30436
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Browsing Eye / Vision by Author "Li, Linya"
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Item Evaluation of Neuroprotective Effect of hybrid compound SA-2 Nanosuspension in Optic Nerve Crush Mouse Model.(2021) Amankwa, Charles E.; Gondi, Sudershan; Funk, Arlene; Debnath, Biddut; Zhang, Wei; Li, Linya; Ferguson, Jonathan; Johnson, Gretchen; Ellis, Dorette; Stankowska, Dorota; Acharya, SuchismitaThis study examines the cytoprotective effects of hybrid antioxidant-nitric oxide (NO) donating compound SA-2 nanosuspension in normal trabecular meshwork-5 cells (NTM-5) and optic nerve crush (ONC) induced-mouse retinal ganglion cell (RGC) death model. SA-2 was encapsulated in poly-lactic-co-glycolic acid (PLGA) nanoparticles and reported earlier. Total nitrite concentrations of SA-2-NPs was determined using Griess assay in both buffer and NTM-5 cell supernatants. NTM-5 cells were treated with tert-butyl hydrogen peroxide (TBHP, EC50 = 5.5mM) at varying concentrations of SA-2 NPs (1, 0.5, 0.25, 0.125 % w/v) and cell viability was measured. 12-week-old C57BL/6J mice were subjected to ONC injury in the left eye and were administered with either vehicle or 1% SA-2-NPs via intravitreal injections (2uL) or eye drops (5uL). Pattern ERG (PERG) was used to assess retinal function and RGC survival was determined using RBPMS-positive RGCs. Data were presented as mean ± SEM, n=3-8. 1% SA-2-NPs dose dependently increased NTM-5 cell viability and total nitrite concentrations (~50%) lasting over 4 days. There was significant improvement in PERG amplitudes (1.7-1.9 times) following SA-2-NP administration as well as increased RGC numbers (by ~20%) relative to ONC-ed eyes. SA-2 nanosuspension shows strong positive trend in protecting RGC's from oxidative stress-induced apoptosis in ONC rodent model. Further investigation is being done for improved dosing and signaling changes in response to SA-2 NPs therapy.Item Novel Compound SA-21 with Antioxidant Capability - The Prospect for Neuroprotection in Glaucoma.(2021) Ferguson, Jonathan; Johnson, Gretchen; Amankwa, Charles E.; Zhang, Wei; Li, Linya; Gondi, Sudershan; Funk, Arlene; Ellis, Dorette; Acharya, Suchismita; Stankowska, DorotaPurpose: Current treatments for glaucoma do not fully address neurodegeneration of retinal ganglion cells (RGCs). Our objective was to determine if compound SA-21, a hybrid superoxide dismutase and glutathione mimetic, could inhibit death of trabecular meshwork cells (NTM5), RGCs and rescue the functional decline of RGCs in an optic nerve crush (ONC) model. Methods: The structure of SA-21 was confirmed by magnetic resonance (NMR) spectroscopy and mass spectrometry. Reactive oxygen species (ROS) release was performed using pyrogallol assay. NTM5 cells were oxidatively stressed with TBHP (5.5mM) or vehicle in the presence of SA-21 (1mM, 100µM, 10µM, 1µM) for 24h. Cell survival was assessed by MTT assay. C57BL6 male mice (12-weeks old, n=4-5) were anesthetized, underwent ONC surgery, and at day 0 and 3 were intravitreally injected with 1% SA-21 (2µl) or vehicle. On day 7, pattern electroretinogram (PERG) was performed, animals were euthanized, and the number of surviving RBPMS-positive RGCs were counted. Results: SA-21 (1mM) treatment significantly decreased ROS production (~50%) measured by pyrogallol assay and increased NTM5 cell viability (~20%, p< 0.0094) following TBHP treatment compared to cells treated with the vehicle. ONC produced a 48% loss of RGCs, which was decreased in SA-21 treated mice (by ~10%) and demonstrated a trend in increase in PERG amplitude. Conclusions: SA-21 compound has antioxidant capability and protects NTM5 cells from oxidative stress. Intravitreally injected SA-21 at the selected dose in mice demonstrated trend in neuroprotection but further investigation is required.