Editors Selection IGR 20-2

Basic Science: Neuroprotection

Ningli Wang

Comment by Ningli Wang on:

79745 Reduced Cerebrospinal Fluid Inflow to the Optic Nerve in Glaucoma, Mathieu E; Gupta N; Paczka-Giorgi LA et al., Investigative Ophthalmology and Visual Science, 2018; 59: 5876-5884

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There is significant evidence suggesting that the trans-lamina cribrosa pressure gradient (TLCPG) contributes to the glaucomatous optic neuropathy in primary open-angle glaucoma.1 Moreover, many studies have confirmed that the circulation of cerebrospinal fluid (CSF) can be affected by the increase of the TLCPG, such as compartment syndrome,2 which may play crucial roles in nutrient delivery and clearance of metabolic waste of the optic nerve.

In this study, Prof. Yücel and colleagues demonstrated that the CSF circulating around the optic nerve is not just in the subarachnoid space, but also enters the optic nerve itself via spaces surrounding blood vessels. Using a mouse model, they also found that CSF entry into the optic nerve is impaired in glaucoma. What makes this study particularly important is that it is the first to confirm that circulation of CSF around the axons of the optic nerve can be affected due to an increase of the TLCPG.

This research has made a significant contribution in the way we understand TLCPG from the perspective of toxic damage. On the basis of this research, we can speculate that there is an accumulation of toxins in the impaired CSF which may induce optic nerve damage in glaucoma. More importantly, this study has identified a potential new CSF-related mechanism in the pathogenesis of glaucoma. However, further study is still needed to elucidate the relationship between reduced CSF flow in the optic nerve and the accumulation of toxic metabolites in the optic nerve in glaucoma. If validated, it represents an important new target in the treatment of glaucoma.


  1. Jonas JB, Wang N, Yang D, et al. Facts and myths of cerebrospinal fluid pressure for the physiology of the eye. Prog Retin Eye Res. 2015;46:67-83.
  2. Killer HE, Miller NR, Flammer J, et al. Cerebrospinal fluid exchange in the optic nerve in normal-tension glaucoma. Br J Ophthalmol. 2012;96(4):544-548.

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