Evaluation of Neuroprotective Effect of hybrid compound SA-2 Nanosuspension in Optic Nerve Crush Mouse Model.

Date

2021

Authors

Amankwa, Charles E.
Gondi, Sudershan
Funk, Arlene
Debnath, Biddut
Zhang, Wei
Li, Linya
Ferguson, Jonathan
Johnson, Gretchen
Ellis, Dorette
Stankowska, Dorota

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0000-0002-1120-7053 (Amankwa, Charles E.)

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Abstract

This 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.

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Research Appreciation Day Award Winner - 2021 Graduate School of Biomedical Sciences, North Texas Eye Research Institute Graduate Student - 2nd Place

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