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Volume 11
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10.3390/cells11233741
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Article

Neuroprotection of Rodent and Human Retinal Ganglion Cells In Vitro/Ex Vivo by the Hybrid Small Molecule SA-2

by
Jennifer H. Pham
1,2,
Gretchen A. Johnson
1,2,
Rajiv S. Rangan
1,2,
Charles E. Amankwa
1,2,
Suchismita Acharya
1,2,* and
Dorota L. Stankowska
1,2,*
1
Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
2
The North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
*
Authors to whom correspondence should be addressed.
Cells 2022, 11(23), 3741; https://doi.org/10.3390/cells11233741
Submission received: 17 October 2022 / Revised: 19 November 2022 / Accepted: 21 November 2022 / Published: 23 November 2022
(This article belongs to the Special Issue Understanding Retinopathy at the Neuro-Glial-Vascular Intersection: Mechanisms, and Potential Therapeutic Targets)
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Abstract

The mechanisms underlying the neuroprotective effects of the hybrid antioxidant-nitric oxide donating compound SA-2 in retinal ganglion cell (RGC) degeneration models were evaluated. The in vitro trophic factor (TF) deprivation model in primary rat RGCs and ex vivo human retinal explants were used to mimic glaucomatous neurodegeneration. Cell survival was assessed after treatment with vehicle or SA-2. In separate experiments, tert-Butyl hydroperoxide (TBHP) and endothelin-3 (ET-3) were used in ex vivo rat retinal explants and primary rat RGCs, respectively, to induce oxidative damage. Mitochondrial and intracellular reactive oxygen species (ROS) were assessed following treatments. In the TF deprivation model, SA-2 treatment produced a significant decrease in apoptotic and dead cell counts in primary RGCs and a significant increase in RGC survival in ex vivo human retinal explants. In the oxidative stress-induced models, a significant decrease in the production of ROS was observed in the SA-2-treated group compared to the vehicle-treated group. Compound SA-2 was neuroprotective against various glaucomatous insults in the rat and human RGCs by reducing apoptosis and decreasing ROS levels. Amelioration of mitochondrial and cellular oxidative stress by SA-2 may be a potential therapeutic strategy for preventing neurodegeneration in glaucomatous RGCs.
Keywords: neuroprotection; glaucoma; retinal ganglion cells; oxidative stress; neurotrophic factor; apoptosis; reactive oxygen species; mitochondria; endothelin neuroprotection; glaucoma; retinal ganglion cells; oxidative stress; neurotrophic factor; apoptosis; reactive oxygen species; mitochondria; endothelin
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MDPI and ACS Style

Pham, J.H.; Johnson, G.A.; Rangan, R.S.; Amankwa, C.E.; Acharya, S.; Stankowska, D.L. Neuroprotection of Rodent and Human Retinal Ganglion Cells In Vitro/Ex Vivo by the Hybrid Small Molecule SA-2. Cells 2022, 11, 3741. https://doi.org/10.3390/cells11233741

AMA Style

Pham JH, Johnson GA, Rangan RS, Amankwa CE, Acharya S, Stankowska DL. Neuroprotection of Rodent and Human Retinal Ganglion Cells In Vitro/Ex Vivo by the Hybrid Small Molecule SA-2. Cells. 2022; 11(23):3741. https://doi.org/10.3390/cells11233741

Chicago/Turabian Style

Pham, Jennifer H., Gretchen A. Johnson, Rajiv S. Rangan, Charles E. Amankwa, Suchismita Acharya, and Dorota L. Stankowska. 2022. "Neuroprotection of Rodent and Human Retinal Ganglion Cells In Vitro/Ex Vivo by the Hybrid Small Molecule SA-2" Cells 11, no. 23: 3741. https://doi.org/10.3390/cells11233741

APA Style

Pham, J. H., Johnson, G. A., Rangan, R. S., Amankwa, C. E., Acharya, S., & Stankowska, D. L. (2022). Neuroprotection of Rodent and Human Retinal Ganglion Cells In Vitro/Ex Vivo by the Hybrid Small Molecule SA-2. Cells, 11(23), 3741. https://doi.org/10.3390/cells11233741

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