Dysfunction of axonal transport in normal-tension glaucoma: a biomarker of disease progression and a potential therapeutic target

Citation metadata

Date: Mar. 2021
From: Neural Regeneration Research(Vol. 16, Issue 3)
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Report
Length: 2,483 words
Lexile Measure: 1480L

Document controls

Main content

Article Preview :

Byline: Kazuyuki. Hirooka, Tohru. Yamamoto, Yoshiaki. Kiuchi

Glaucoma and dysfunction of axonal transport: One of the leading causes of irreversible blindness worldwide is glaucoma, with increased intraocular pressure (IOP) being the most common risk factor. However, in some glaucoma patients it has been shown that the IOP does not differ from that of the normal population. In Japan, normal-tension glaucoma (NTG), which accounts for 92% of primary open-angle glaucoma, has been shown to be more frequent in the population. Primarily, open-angle glaucoma treatments are almost exclusively focused on lowering the IOP through the use of drugs, laser therapy or surgery. However, glaucomatous optic nerve changes are believed by many investigators to occur not only due to increases in the IOP, but also because of other factors that are unrelated to the IOP, and which can play significant roles in some of these NTG cases. Glaucoma is a disease that causes vision loss through the degeneration and eventual apoptotic death of retinal ganglion cells (RGCs). The complex and multifactorial diseases caused by glaucoma are likely the result of the convergence of several molecular pathways that then induce RGC loss. Human glaucoma studies have demonstrated the presence of impaired axonal transport along the RGCs (Knox et al., 2007). Furthermore, since axonal transport is known to have a critical role with regard to the survival of RGCs, glaucomatous optic neuropathy may be associated with a failure of this transport. It has been clearly demonstrated that impaired axonal transport is an early, reversible, sensitive change in injured RGCs that precedes cell death (Fahy et al., 2016). Brain-derived neurotrophic factor, nerve growth factor, ciliary neurotrophic factor, and glial cell line-derived neurotrophic factor all help to both mediate the activity and ensure the survival of the RGCs. Other neurotrophic factors, such as fibroblast growth factor-2, neurotrophin 3, neurotrophin 4, and interleukin-10 have all been found to be neuroprotective in RGCs (Nafissi and Foldvari, 2016). The initial pathological events that are normally observed in neurodegenerative disorders include impairment of axonal transport, as the transduction of trophic signals requires the presence of intact axonal transport. Therefore, one of the attractive treatment areas when attempting to stop the RGC loss in glaucoma is to address the changes associated with the neurotrophic factor deprivation or adjust the insufficient levels of other essential molecules in order to prevent any axonal transport blockade.

Glaucoma and Alzheimer's diseases (AD): AD is defined as a progressive neurodegenerative disorder. This disease is associated with changes in personality, cognitive and memory deteriorations, and an impaired ability to perform routine daily activities. The loss of neurons in the hippocampus and cerebral cortex that occurs in AD patients has been reported to be caused by plaque accumulation in the brain related to abnormally folded amyloid [sz] (A[sz]) and tau protein. Results from transgenic AD animal models have reported finding that there is synaptic dysfunction and axonal pathology that occurs before the deposition of the amyloid plaques and tau aggregation. Along with these findings, the brain areas affected in...

Source Citation

Source Citation   

Gale Document Number: GALE|A636783714