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Muneeb A Faiq, Vishnu Adi, Sophia Khoja, Anoop Sainulabdeen, Russell W Chan, Carlos Parra, Giles Hamilton-Fletcher, Choong H Lee, Jiangyang Zhang, Gadi Wollstein, Joel Schuman, Kevin C Chan; Entry of cerebrospinal fluid components into the anterior chamber of the eye. Invest. Ophthalmol. Vis. Sci. 2021;62(11):37.
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Recent evidence suggested the close interplay between intraocular pressure and intracranial pressure in health and disease, yet whether and how cerebrospinal fluid (CSF) communicates with the eye remains unclear. Here, we used in vivo contrast-enhanced MRI (CE-MRI) to investigate the entry of CSF components into the eye.
A polyethylene tubing was placed intrathecally at the lumbar region (L4-L5) of 34 healthy adult C57BL/6J mice followed by CE-MRI using a 7-Tesla Bruker scanner. Group 1 (n=20) received Gd-DTPA (molecular weight=0.9kDa) as contrast agent and Group 2 (n=14) received GadoSpin (molecular weight=200kDa). During MRI, animals were maintained under 1.0%-1.5% isoflurane at 37±1 oC rectal temperature. Contrast dynamics was monitored using a 3D T1-weighted sequence with 78x78x78 µm3 isotropic resolution. Twelve continuous scans (each lasting 10 min) were performed with 3 baseline acquisitions followed by 30 min of contrast infusion into the CSF space via the catheter while scanning continued until the 12th timepoint. T1-weighted contrast intensity (CI) changes over time were quantified in 7 regions of interest (ROIs) and compared within and between groups. These ROIs included posterior optic nerve subarachnoid space (ONSAS-P) distal to the eye, anterior ONSAS (ONSAS-A) proximal to the eye, olfactory bulb (OB), muscle tissue (MT), vitreous, lens, and anterior chamber (AC) (Fig. 1).
Between-group ANOVAs were significant for ONSAS-P, ONSAS-A, OB, and AC (all p’s<.001), and NS for other ROIs. Bonferroni-corrected independent t-tests comparing each ROI between groups revealed that Group 1 had significantly higher CI than Group 2 for ONSAS-P [t(27.72)=13.05, p<.001, Mean difference (Mdiff)=474.27, d=4.27], ONSAS-A [t(32)=6.12, p<.001, Mdiff=146.15, d=2.11], OB [t(32)=5.96, p<.001, Mdiff=194.98, d=2.17] and AC [t(24.25)=4.02, p=.004, Mdiff=217.25, d=1.30] respectively. Time-to-peak was significantly different between groups for ONSAS-P [p<.001, Mdiff=29.71], ONSAS-A [p<.001, Mdiff=29.43], and AC [p=0.004, Mdiff=-8.21] (Fig. 2).
CSF components can enter the AC and possibly affect the composition of aqueous humor in a molecular size-dependent manner. Further studies are required to probe the pathways of this CSF-aqueous communication and its role in central and ocular physiology and diseases.
This is a 2021 Imaging in the Eye Conference abstract.
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