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Browsing Abstracts by Author "Acharya, Suchismita"
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Item Neuroprotection of Rodent Retinal Ganglion Cells using Hybrid Molecule SA-10(2023) Pham, Jennifer H.; Kodati, Bindu; Johnson, Gretchen A.; Acharya, Suchismita; Stankowska, Dorota L.Purpose: Oxidative stress is the imbalance between the activity of antioxidants and free radical production, which has been shown to be associated with glaucomatous retinal ganglion cell (RGC) degeneration. In this study, we aimed to promote RGC survival by treatment with SA-10, a second-generation hybrid molecule with nitric oxide donating and sulfone reactive oxygen species (ROS) scavenging moieties in vitro and ex vivo following oxidative stress-induced injury. Methods: Endothelin-3, a vasoactive peptide, was used to induce oxidative stress in vitro in rat primary RGCs (n=3 biological replicates) and ex vivo in C57BL/6J mice retinal explants (n=8-9 explants/group). Primary RGCs were isolated from Sprague Dawley rat pups (post-natal days 4-7) and cultured for seven days with neurotrophic factors to allow for neurite outgrowth. The RGCs and retinal explants were pretreated with vehicle (DPBS) or SA-10 [10 µM] for 30 minutes, following which ET-3 treatment [100 nM or 400 nM] was carried out for 1 hour. CellROX™ Green was then used to stain for ROS produced by the cells, and the integrated density was analyzed. Analysis of Variance (ANOVA) or nonparametric Kruskal-Wallis was performed for all experiments. Results: In primary RGCs, ET-3-mediated ROS production decreased by 25.9% (p<0.01) following SA-10 treatment compared to the vehicle. In mice, retinal explants, 400 nM ET-3 induced a 24.4% increase in ROS production compared to the vehicle [0 nM ET-3]. With the SA-10 treatment, the ROS production was decreased by 14.74% (p<0.001) in the ET-3 and SA-10 treated group compared to the ET-3-only treated group. Conclusion: SA-10 effectively protects rodent RGCs in vitro and ex vivo from ET-3-mediated oxidative stress.Item The Neuroprotective Effects of Hybrid SA-10 Nanoparticles in a Glaucoma Mouse Model of Retinal Ischemia/Reperfusion Injury(2023) Le, Kim-Tuyen T.; Zhang, Wei; Pham, Jennifer H.; Kodati, Bindu; Amankwa, Charles E.; Engelland, Rachel E.; Hatfield, Brendon R.; Acharya, Suchismita; Stankowska, Dorota L.Purpose: The progression of glaucoma is largely dependent on the gross functionality of retinal ganglion cells (RGCs), which transmit visual signals to the brain. Current treatments for glaucoma focus on lowering intraocular pressure (IOP), yet other risk factors such as oxidative stress and poor blood perfusion also contribute to RGC damage. Furthermore, no treatments exist which revitalize dysfunctional RGCs. One promising neuroprotective agent is SA-10, a hybrid compound with reactive oxygen species (ROS) scavenging sulfone moiety and perfusion-enhancing nitric oxide (NO) donor moiety. This study aims to investigate the in vivoneuroprotective effects of the nanoparticle (NP) formulation of SA-10 (SA-10-NPs) on RGCs in an acute rodent model of ischemia/reperfusion (I/R). Methods: C57BL/6J mice were separated into 3 groups (n= 5-8 per group): Sham control, 1% Blank NPs-treated, and 1% SA-10-NPs. Aside from sham, all groups received 4 μL of different blinded topical pre-treatments: poly(lactic-co-glycolic-acid) (PLGA) nanoparticles suspended PBS for the Blank-NPs group, and 1% SA-10 loaded in PLGA for the SA-10-NPs group. Besides the sham, all groups had their anterior chambers cannulated with normal saline to achieve an elevated IOP of 120 mmHg for 60 minutes. After I/R all groups received 4 μL of their respective treatments 3 times a week over 14 days. Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) tests were independently performed both prior to I/R insult (baseline) and after completing the treatment regimen. Mouse eyes were then enucleated. Their retinas were stained with an RNA binding protein with multiple splicing (RBPMS) RGC-specific marker for quantification of cell survival. Parametric Analysis of Variance (ANOVA) and its non-parametric equivalent, the Kruskal-Wallis test, were performed for statistical analysis. Results: I/R injury (Blank-NPs-treated) produced a 52.1% decline (p<0.01) in PERG and a 17.9% decreasing trend in PVEP amplitudes as compared to sham. SA-10-NPs prevented this decline by a trend of 33.5% and 14%, respectively. I/R injury (Blank NPs-treated) caused a 33% decrease (p<0.01) in RGC survival in the inner retina in comparison with sham control, which was alleviated with the SA-10-NPs treatment by 33.4% (p<0.001). Conclusions: SA-10-NPs enhanced RGC survival and function following ischemia-induced damage in the mice I/R model and have the potential to be used as a neuroprotective therapy for glaucoma.