This website uses cookies to help us give you the best browsing experience. By continuing to use this portal, you agree to our use of this tool.
To learn more about how we use cookies and how to manage them please read our notice here.
Journal Club
Experimental Paper of the Month - Reduced Cerebrospinal Fluid Inflow to the Optic Nerve in Glaucoma
Reduced Cerebrospinal Fluid Inflow to the Optic Nerve in Glaucoma

Publishing date: January 2019

Author(s): Mathieu E (1,2,3), Gupta N (1,2,3,4,5), Paczka-Giorgi LA (1,2), Zhou X (1,2), Ahari A (1,2), Lani R (1), Hanna J (1,2,3), YĆ¼cel YH (1,2,3,6,7,8)

1 Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
2 Department of Ophthalmology and Vision Sciences, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
3 Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
4 Glaucoma Unit, St. Michael's Hospital, Toronto, Ontario, Canada.
5 Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
6 Department of Physics, Faculty of Science, Ryerson University, Toronto, Ontario, Canada.
7 Faculty of Engineering and Architectural Science, Ryerson University, Toronto, Ontario, Canada.
8 Institute of Biomedical Engineering, Science and Technology (iBEST), St. Michael's Hospital, Ryerson University, Toronto, Ontario, Canada.

Purpose: To determine whether cerebrospinal fluid (CSF) entry into the optic nerve is altered in glaucoma.

Methods: Fluorescent 10-kDa dextran tracer was injected into the CSF of 2-month-old (n = 9) and 10-month-old DBA/2J glaucoma mice (n = 8) and age-matched controls (C57Bl/6; n = 8 each group). Intraocular pressure (IOP) was measured in all mice before tracer injection into CSF. Tracer distribution was assessed using confocal microscopy of optic nerve cross-sections of mice killed 1 hour after injection. Paravascular tracer distribution in the optic nerve was studied in relation to isolectin-stained blood vessels. Tracer intensity and cross-sectional area in the laminar optic nerve were quantitatively assessed in all four groups and statistically compared. Aquaporin 4 (AQP4) and retinal ganglion cell axonal phosphorylated neurofilament (pNF) were evaluated using immunofluorescence and confocal microscopy.

Results: IOP was elevated in 10-month-old glaucoma mice compared with age-matched controls. One hour after tracer injection, controls showed abundant CSF tracer in the optic nerve subarachnoid space and within the nerve in paravascular spaces surrounding isolectin-labeled blood vessels. CSF tracer intensity and signal distribution in the optic nerve were significantly decreased in 10-month-old glaucoma mice compared with age-matched controls (P = 0.0008 and P = 0.0033, respectively). AQP4 immunoreactivity was similar in 10-month-old DBA and age-matched control mice. Half of the 10-month-old DBA mice (n = 4/8) showed a decrease in pNF immunoreactivity compared to controls. Altered pNF staining was seen only in DBA mice lacking CSF tracer at the laminar optic nerve (n = 4/5).

Conclusions: This study provides the first evidence that CSF entry into the optic nerve is impaired in glaucoma. This finding points to a novel CSF-related mechanism that may help to understand optic nerve damage in glaucoma.

Invest Ophthalmol Vis Sci. 2018 Dec 3;59(15):5876-5884. doi: 10.1167/iovs.18-24521.

http://www.ncbi.nlm.nih.gov/pubmed/30543343



Experimental Paper of the Month manager: Andreas Boehm




back to top

X