The Neuroprotective Effects of Hybrid SA-10 Nanoparticles in a Glaucoma Mouse Model of Retinal Ischemia/Reperfusion Injury




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.


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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).


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.


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).


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.


Research Appreciation Day Award Winner - School of Biomedical Sciences, 2023 North Texas Eye Research Institute Graduate Student Award - 1st Place