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Peer-reviewedCC BYNeurotherapeutics

Targeting prostaglandin catabolism via topical nanotherapy rescues vision in ischemic optic neuropathy

  • Shweta Modgil1
  • RuSiou Hsu2
  • Mohammad Ali Shariati1
  • Juan A. Oses-Prieto3
  • Al Burlingame3
  • Yaping Joyce Liao4
4 affiliations
  1. 1Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA
  2. 2Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA; Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan
  3. 3Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA
  4. 4Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA; Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA; Corresponding author.
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Abstract

Ischemic optic neuropathy is a leading cause of acute vision loss and currently lacks effective therapy. Here, we identify 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme responsible for prostaglandin degradation, as a metabolic checkpoint in ischemic optic neurodegeneration. Analysis of human ischemic optic nerve tissue and a murine model of optic nerve ischemia reveals marked upregulation of retinal 15-PGDH, suggesting dysregulated prostaglandin homeostasis after ischemic injury. To therapeutically target this pathway, we develop a nano-micellar formulation of the hydrophobic 15-PGDH inhibitor SW033291 (SW@NM) that enables efficient topical ocular delivery and retinal penetration. Topical administration of SW@NM suppresses retinal 15-PGDH activity, restores PGE 2 levels, preserves retinal ganglion cells and optic nerve axons, and significantly improves visual function after ischemic injury. Mechanistically, 15-PGDH inhibition suppresses ferroptosis-associated lipid peroxidation and preserves mitochondrial integrity, thereby mitigating ischemia-induced neurodegeneration. Collectively, these findings establish 15-PGDH–mediated prostaglandin catabolism as a therapeutic target in ischemic optic neuropathy and demonstrate a clinically translatable nanotherapeutic strategy for protecting the central nervous system from ischemic neurodegeneration.

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Cite

BibTeXRIS
BibTeX
@article{modgil2026targeting,
  title = {{Targeting prostaglandin catabolism via topical nanotherapy rescues vision in ischemic optic neuropathy}},
  author = {Shweta Modgil and RuSiou Hsu and Mohammad Ali Shariati and Juan A. Oses-Prieto and Al Burlingame and Yaping Joyce Liao},
  journal = {Neurotherapeutics},
  year = {2026},
  month = oct,
  doi = {10.1016/j.neurot.2026.e01065},
  url = {https://doi.org/10.1016/j.neurot.2026.e01065},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Targeting prostaglandin catabolism via topical nanotherapy rescues vision in ischemic optic neuropathy
AU  - Shweta Modgil
AU  - RuSiou Hsu
AU  - Mohammad Ali Shariati
AU  - Juan A. Oses-Prieto
AU  - Al Burlingame
AU  - Yaping Joyce Liao
PY  - 2026
DA  - 2026/10/24
JO  - Neurotherapeutics
DO  - 10.1016/j.neurot.2026.e01065
UR  - https://doi.org/10.1016/j.neurot.2026.e01065
AB  - Ischemic optic neuropathy is a leading cause of acute vision loss and currently lacks effective therapy. Here, we identify 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme responsible for prostaglandin degradation, as a metabolic checkpoint in ischemic optic neurodegeneration. Analysis of human ischemic optic nerve tissue and a murine model of optic nerve ischemia reveals marked upregulation of retinal 15-PGDH, suggesting dysregulated prostaglandin homeostasis after ischemic injury. To therapeutically target this pathway, we develop a nano-micellar formulation of the hydrophobic 15-PGDH inhibitor SW033291 (SW@NM) that enables efficient topical ocular delivery and retinal penetration. Topical administration of SW@NM suppresses retinal 15-PGDH activity, restores PGE 2 levels, preserves retinal ganglion cells and optic nerve axons, and significantly improves visual function after ischemic injury. Mechanistically, 15-PGDH inhibition suppresses ferroptosis-associated lipid peroxidation and preserves mitochondrial integrity, thereby mitigating ischemia-induced neurodegeneration. Collectively, these findings establish 15-PGDH–mediated prostaglandin catabolism as a therapeutic target in ischemic optic neuropathy and demonstrate a clinically translatable nanotherapeutic strategy for protecting the central nervous system from ischemic neurodegeneration.
SN  - 1878-7479
SN  - 1933-7213
ER  -