Glaucoma as a Tauopathy—Is It the Missing Piece in the Glaucoma Puzzle?

Abstract

Glaucoma is a chronic neurodegenerative disorder affecting the visual system which can result in vision loss and blindness. The pathogenetic mechanisms underlying glaucomatous optic neuropathy are ultimately enigmatic, prompting ongoing investigations into its potential shared pathogenesis with other neurodegenerative neurological disorders. Tauopathies represent a subclass of neurodegenerative diseases characterized by the abnormal deposition of tau protein within the brain and consequent microtubule destabilization. The extended spectrum of tauopathies includes conditions such as frontotemporal dementias, progressive supranuclear palsy, chronic traumatic encephalopathy, and Alzheimer’s disease. Notably, recent decades have witnessed emerging documentation of tau inclusion among glaucoma patients, providing substantiation that this ocular disease may similarly manifest features of tauopathies. These studies found that: (i) aggregated tau inclusions are present in the somatodendritic compartment of RGCs in glaucoma patients; (ii) the etiology of the disease may affect tau splicing, phosphorylation, oligomerization, and subcellular localization; and (iii) short interfering RNA against tau, administered intraocularly, significantly decreased retinal tau accumulation and enhanced RGC somas and axon survival, demonstrating a crucial role for tau modifications in ocular hypertension-induced neuronal injury. Here, we examine the most recent evidence surrounding the interplay between tau protein dysregulation and glaucomatous neurodegeneration. We explore the novel perspective of glaucoma as a tau-associated disorder and open avenues for cross-disciplinary collaboration and new treatment strategies.

Targeting shared pathways in tauopathies and age-related macular degeneration: implications for novel therapies

“…We believe that this observation will aid many other degenerative eye disorders (such as ocular scarring pemphigoid, OCP, or glaucoma) (Passaro et al, 2023) by elucidating the shared pathophysiology (DNA damage and inflammation associated with senescence).…”

“…Overall, the resemblance in physiological characteristics between the brain and the retina underscores their shared evolutionary origins and interconnected roles in processing sensory information to support various nervous system functions ( Mahabadi and Al Khalili, 2023 ). As neuropathological changes in retinal neurons might mirror brain pathology, a growing hypothesis has suggested its potential role as a “window to the brain” in recent years ( Chiquita et al, 2019 ; Passaro et al, 2023 ). It engages in intricate processing of visual stimuli before their transmission to the brain.…”

Targeting the Cerebrospinal Fluid Compartment in Glaucoma: Still the Dark Side of the Moon? Comment on Passaro et al. Glaucoma as a Tauopathy—Is It the Missing Piece in the Glaucoma Puzzle? J. Clin. Med. 2023, 12, 6900

“…I read with great interest the article by Passaro et al [1] exploring the novel perspective of glaucoma as a tau-associated disorder and shedding light on potential new therapeutic avenues for this disease through targeting various pathogenic pathways involved in tauopathies. I would like to congratulate the authors for establishing this informative review and would appreciate the opportunity to make a comment.…”

Reply to Wostyn, P. Targeting the Cerebrospinal Fluid Compartment in Glaucoma: Still the Dark Side of the Moon? Comment on “Passaro et al. Glaucoma as a Tauopathy—Is It the Missing Piece in the Glaucoma Puzzle? J. Clin. Med. 2023, 12, 6900”

“…We are grateful to the author of the comment [ 1 ] who has kindly taken the time to comment on our review article [ 2 ]. The insightful commentary provided offers profound illumination for our paper, provoking thoughtful reflections on its content.…”