Increased ER Stress After Experimental Ischemic Optic Neuropathy and Improved RGC and Oligodendrocyte Survival After Treatment With Chemical Chaperon
| Autor: | Louise A. Mesentier-Louro, Varun Kumar, Kathleen Heng, Mohammad Ali Shariati, Yaping Joyce Liao, Haoliang Huang, Angela Oh, Yang Hu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Retinal Ganglion Cells genetic structures CHOP Optic neuropathy Mice 0302 clinical medicine Medicine retinal ganglion cell Endoplasmic Reticulum Chaperone BiP Heat-Shock Proteins unfolded protein response Endoplasmic Reticulum Stress Phenylbutyrates endoplasmic reticulum 4-phenylbutyric acid Oligodendroglia medicine.anatomical_structure Optic nerve Female ER stress medicine.medical_specialty chaperon Optic Disk Retinal ganglion 03 medical and health sciences Internal medicine Animals Optic Neuropathy Ischemic AION Retina Eye Movements Strabismus Amblyopia and Neuro-Ophthalmology business.industry Ischemic optic neuropathy medicine.disease eye diseases optic neuropathy Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology OCT Gene Expression Regulation Unfolded protein response Anterior ischemic optic neuropathy metabolic stress sense organs business 030217 neurology & neurosurgery Transcription Factor CHOP Molecular Chaperones |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 0146-0404 |
| Popis: | Purpose Increased endoplasmic reticulum (ER) stress is one of the earliest subcellular changes in neuro-ophthalmic diseases. In this study, we investigated the expression of key molecules in the ER stress pathways following nonarteritic anterior ischemic optic neuropathy (AION), the most common acute optic neuropathy in adults over 50, and assessed the impact of chemical chaperon 4-phenylbutyric acid (4-PBA) in vivo. Methods We induced AION using photochemical thrombosis in adult mice and performed histologic analyses of key molecules in the ER stress pathway in the retina and optic nerve. We also assessed the effects of daily intraperitoneal injections of 4-PBA after AION. Results In the retina at baseline, there was low proapoptotic transcriptional regulator C/EBP homologous protein (CHOP) and high prosurvival chaperon glucose-regulated protein 78 (GRP78) expression in retinal ganglion cells (RGCs). One day after AION, there was significantly increased CHOP and reduced GRP78 expressions in the ganglion cell layer. In the optic nerve at baseline, there was little CHOP and high GRP78 expression. One day after AION, there was significantly increased CHOP and no change in GRP78 expression. Treatment immediately after AION using daily intraperitoneal injection of chemical chaperone 4-PBA for 19 days significantly rescued Brn3A+ RGCs and Olig2+ optic nerve oligodendrocytes. Conclusions We showed for the first time that acute AION resulted in increased ER stress and differential expression of ER stress markers CHOP and GRP78 in the retina and optic nerve. Rescue of RGCs and oligodendrocytes with 4-PBA provides support for ER stress reduction as possible treatment for AION. |
| Databáze: | OpenAIRE |
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