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Muneeb A Faiq, Vishnu Adi, Jingyuan Zhu, Sophia Khoja, Anoop Sainulabdeen, Carlos Parra, Giles Hamilton-Fletcher, Choong H Lee, Jiangyang Zhang, Christopher Kai-Shun Leung, Gadi Wollstein, Joel S Schuman, Kevin Chan; Effects of chronic intraocular pressure elevation on cerebrospinal fluid dynamics in the optic nerve. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1861.
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© ARVO (1962-2015); The Authors (2016-present)
Though chronic intraocular pressure (IOP) elevation and glymphatic disturbances have been implicated in various optic neuropathies, the relation between IOP and optic nerve (ON) cerebrospinal fluid (CSF) dynamics has not been sufficiently investigated. We employed contrast-enhanced MRI (CE-MRI) for in vivo investigation of CSF dynamics in the ON with and without chronic IOP elevation.
IOP was elevated unilaterally in adult C57BL/6J mice (n=15, Group 1) by intracameral injection of in situ cross-linking hydrogel. Chronic IOP elevation in the injected eye (Group 1a) was confirmed at 4 weeks post-injection, at 19.37±3.41 mmHg (mean±SEM) relative to the fellow, untreated eye (Group 1b) at 11.39±3.74 mmHg. Another 20 healthy naive mice received no intervention to either eye (Group 2). A polyethylene tubing was inserted intrathecally at the lumbar region (L4-L5) followed by CE-MRI using a 7-Tesla Bruker BioSpec scanner. Contrast dynamics was monitored using 3D T1-weighted FLASH sequence with an isotropic resolution of 78x78x78 μm3. Twelve 10-min continuous scans were acquired, beginning with 3 baseline acquisitions followed by 30 min of Gd-DTPA contrast infusion while the scanning continued till the 12 timepoint. Change in contrast intensity (CI) over time was quantified in 6 anatomical regions of interest (ROIs) viz. posterior ON subarachnoid space (ONSAS-P), anterior ON SAS (ONSAS-A), posterior ON parenchyma (ONP-P), anterior ON parenchyma (ONP-A), olfactory bulb (OB, positive control), and muscle tissue (MT, negative control).
Between group ANOVAs were significant for each ROI in the ON (all p’s<.001), and not significant for control regions. Post-hocs revealed that for ONSAS-A, Group 1a had lower CI than Group 1b (p<.001) and Group 2 (p<.001), while Groups 1b and 2 also differed (p=.011). For ONP-A, Group 1a had lower CI than Group 1b (p=.003) and Group 2 (p<.001), with no difference between Groups 1b and 2. For ONSAS-P, Groups 1b and 2 CI differed significantly (p=.011), and for ONP-P, Group 1a had lower CI than Group 1b (p<.001) and Group 2 (p=.003), while Groups 1b and 2 CI also differed (p=.004).
Chronic IOP elevation is associated with significant decrease in the CSF flow into the ON SAS and ON parenchyma. CSF dynamics is also altered in the contralateral ON projected from the fellow eye with normal IOP.
This is a 2021 ARVO Annual Meeting abstract.
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