Author's Reply.

Dear Editor,

We appreciate Dr. Wostyn, et al's interest in our manuscript titled, “Senile Dementia and Glaucoma: Evidence for a Common Link”.[1] Dr. Wostyn et al's work in this area is indeed intriguing. Dr. Wostyn et al's hypothesis states that deficient exchange between cerebrospinal fluid and brain interstitial fluid compartments along the optic nerve may allow the accumulation of neurotoxins, including amyloid-β, and subsequently predispose to glaucomatous optic neuropathy.[2] Specifically, this deficiency in waste exchange could occur within a network of diseased paravenous drainage pathways. The glymphatic pathway, as described by Iliff et al, may become dysfunctional due to genetic insult to the Aqp4 gene, which regulates generation of the water channel aquaporin-4 in astrocytes.[3] Animals with deletion of the Aqp4 gene exhibit decreased clearance of amyloid-β via the glymphatic pathway.

Given the potential link between Alzheimer's disease and glaucomatous optic neuropathy, we agree that the aforementioned findings may have important implications regarding the pathophysiology and possible therapy for certain forms of glaucomatous optic neuropathy. It would be interesting to investigate the effects of suppression of the Aqp4 gene on optic nerve health. Possible subsequent glaucomatous optic neuropathy, presumably due to accumulation of amyloid-β via a dysfunctional glymphatic pathway, would strongly support the link between Alzheimer's disease and “normal tension” types of glaucoma. Furthermore, this would offer a potential therapeutic target for both diseases.

Financial Support and Sponsorship

The authors are supported by NIH Core Grant EY001792 and an Unrestricted Grant from Research to Prevent Blindness.

Conflicts of Interest

There are no conflicts of interest.