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Lauren Davis, William O Cepurna, Diana C Lozano, Tiffany E Choe, Elaine C. Johnson, John C Morrison, Shandiz Tehrani; Optic Nerve Head Astrocyte Response to Elevated Intraocular Pressure does not Require Viable Retinal Ganglion Cell Axons. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2023. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Optic nerve head (ONH) astrocytes respond to elevated intraocular pressure (IOP) by structural rearrangement of astrocytic extensions. However, it is unclear whether astrocyte extensions rearrange in response to elevated IOP or to signals from injured retinal ganglion cell axons. This study explored the response of ONH astrocytes to 8 hours of IOP elevation in the presence or absence of optic nerve transection (ONT).
Brown Norway rats (n = 33) were assigned to one of two groups. In the first group, animals underwent unilateral ONT under systemic anesthesia via retrobulbar axotomy of the optic nerve. Two weeks post ONT, 11 of these eyes underwent controlled elevation of IOP (CEI), consisting of anterior chamber cannulation and IOP elevation to 60 mmHg for 8 hours via a saline reservoir. Animals were sacrificed either immediately (day 0) or 1 day post CEI. The remaining ONT animals were sacrificed without CEI (n = 8). In the second group, 14 eyes underwent CEI only with sacrifice at day 0 and day 1. Contralateral eyes served as controls. All eyes were perfusion fixed and longitudinal vertical ONH cryo-sections were co-labeled with fluorescent-tagged phalloidin and tubulin βIII antibody to delineate astrocyte extensions and axons, respectively. Following confocal microscopy, astrocyte extension orientation was determined and quantified relative to the anterior-posterior (AP) axis using FIJI software and ANOVA statistical analysis.
ONT resulted in a loss of observable axon-specific tubulin labeling within the ONH. In control and ONT-only eyes, astrocyte extensions were oriented nearly perpendicular to the AP axis (84.1° ± 1.3 [n=7] and 72.8° ± 4.7 [n=7], respectively, no significant difference). Immediately following CEI (day 0), astrocyte extensions rearranged to lie more parallel to the AP axis relative to controls in both CEI-only and ONT+CEI eyes (43.18° ± 13.3 [n=7, p ≤ 0.01] and 54.43° ± 16.0 [n=7, p <0.05], respectively). Astrocyte extensions reoriented back to control levels 1 day post CEI in both CEI-only and ONT+CEI eyes.
These results suggest that astrocyte structural arrangements within the ONH primarily respond to IOP elevation rather than through a secondary response triggered by axonal injury. As such, the relatively early structural response of ONH astrocytes to elevated IOP may play a primary role in influencing axonal injury.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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