Early Optic Nerve Head Glial Proliferation and Jak-Stat Pathway Activation in Chronic Experimental Glaucoma
| Autor: | John C. Morrison, Tiffany E. Choe, William O. Cepurna, Elaine C. Johnson, Diana C Lozano |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male STAT3 Transcription Factor Intraocular pressure Pathology medicine.medical_specialty genetic structures Optic Disk Optic disk Glaucoma optic nerve 03 medical and health sciences Tonometry Ocular 0302 clinical medicine Rats Inbred BN Glial Fibrillary Acidic Protein medicine Animals Intraocular Pressure Janus Kinases Microglia business.industry SOXB1 Transcription Factors PAX2 Transcription Factor JAK-STAT signaling pathway medicine.disease Immunohistochemistry eye diseases animal models Rats 030104 developmental biology medicine.anatomical_structure cell proliferation nervous system Astrocytes Optic Nerve Injuries Chronic Disease Models Animal Optic nerve sense organs business Neuroglia 030217 neurology & neurosurgery Biomarkers Astrocyte Signal Transduction |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 0146-0404 |
| Popis: | Purpose We previously reported increased expression of cell proliferation and Jak-Stat pathway-related genes in chronic experimental glaucoma model optic nerve heads (ONH) with early, mild injury. Here, we confirm these observations by localizing, identifying, and quantifying ONH cellular proliferation and Jak-Stat pathway activation in this model. Methods Chronic intraocular pressure (IOP) elevation was achieved via outflow pathway sclerosis. After 5 weeks, ONH longitudinal sections were immunolabeled with proliferation and cell-type markers to determine nuclear densities in the anterior (unmyelinated) and transition (partially myelinated) ONH. Nuclear pStat3 labeling was used to detect Jak-Stat pathway activation. Nuclear density differences between control ONH (uninjected) and ONH with either early or advanced injury (determined by optic nerve injury grading) were identified by ANOVA. Results Advanced injury ONH had twice the nuclear density (P < 0.0001) of controls and significantly greater astrocyte density in anterior (P = 0.0001) and transition (P = 0.006) ONH regions. An increased optic nerve injury grade positively correlated with increased microglia/macrophage density in anterior and transition ONH (P < 0.0001, both). Oligodendroglial density was unaffected. In glaucoma model ONH, 80% of anterior and 66% of transition region proliferating cells were astrocytes. Nuclear pStat3 labeling significantly increased in early injury anterior ONH, and 95% colocalized with astrocytes. Conclusions Astrocytes account for the majority of proliferating cells, contributing to a doubled nuclear density in advanced injury ONH. Jak-Stat pathway activation is apparent in the early injury glaucoma model ONH. These data confirm dramatic astrocyte cell proliferation and early Jak-Stat pathway activation in ONH injured by elevated IOP. |
| Databáze: | OpenAIRE |
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