Approaches to Potentiated Neuroprotective Treatment in the Rodent Model of Ischemic Optic Neuropathy
| Autor: | Zara Mehrabian, Yan Guo, Steven L. Bernstein, Neil R. Miller, Amanda D. Henderson, Steven Roth |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Retinal Ganglion Cells genetic structures Pharmacology Meloxicam Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine Piperidines Biology (General) retinal ganglion cell rodent General Medicine Neuroprotective Agents medicine.anatomical_structure Retinal ganglion cell Optic nerve lipids (amino acids peptides and proteins) neuroprotection nonarteritic anterior ischemic optic neuropathy (NAION) prostaglandin medicine.drug Prostaglandin Antagonists QH301-705.5 PGJ2 Ischemia Prostaglandin ischemia Neuroprotection Article optic nerve 03 medical and health sciences medicine Animals Optic Neuropathy Ischemic Benzodioxoles business.industry animal model Ischemic optic neuropathy medicine.disease eye diseases Rats Disease Models Animal chemistry inflammation 030221 ophthalmology & optometry gene expression Anterior ischemic optic neuropathy sense organs business 030217 neurology & neurosurgery |
| Zdroj: | Cells Volume 10 Issue 6 Cells, Vol 10, Iss 1440, p 1440 (2021) |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells10061440 |
| Popis: | Nonarteritic anterior ischemic optic neuropathy (NAION) commonly causes sudden optic nerve (ON)-related vision loss. The rodent NAION model (rAION) closely resembles NAION in presentation and physiological responses. We identified early rAION-associated optic nerve head (ONH) inflammatory gene expression responses and the anti-inflammatory prostaglandin PGJ2’s effects on those responses. We hypothesized that blocking pro-inflammatory prostaglandin (PGE2) production by inhibiting monoacylglycerol lipase or cyclooxygenase activity and co-administering PGJ2 would potentiate RGC survival following ischemic neuropathy. Deep sequencing was performed on vehicle- and PGJ2-treated ONHs 3d post-rAION induction. Results were compared against responses from a retinal ischemia model. Animals were treated with PGJ2 and MAGL inhibitor KML29, or PGJ2 + COX inhibitor meloxicam. RGC survival was quantified by stereology. Tissue PG levels were quantified by ELISA. Gene expression was confirmed by qPCR. PGJ2 treatment nonselectively reduced inflammatory gene expression post-rAION. KML29 did not reduce PGE2 1d post-induction and KML29 alone increased RGC loss after rAION. Combined treatments did not improve ONH edema and RGC survival better than reported with PGJ2 alone. KML29′s failure to suppress PGE2 ocular synthesis, despite its purported effects in other CNS tissues may result from alternative PG synthesis pathways. Neither KML29 nor meloxicam treatment significantly improved RGC survival compared with vehicle. While exogenous PGJ2 has been shown to be neuroprotective, treatments combining PGJ2 with these PG synthesis inhibitors do not enhance PGJ2’s neuroprotection. |
| Databáze: | OpenAIRE |
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