Do normal-tension and high-tension glaucoma result from brain and ocular glymphatic system disturbances, respectively?

Wostyn, Peter

doi:10.1038/s41433-020-01219-w

Cited by 9 publications

(7 citation statements)

References 7 publications

(10 reference statements)

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“…It has been proposed that normal tension glaucoma could result from disturbance in the glymphatic pathway in the brain and high-tension glaucoma could result from disturbance in the ocular glymphatic system 33 .…”

Section: Discussionmentioning

confidence: 99%

A novel maxillofacial technique to deliver drugs to the visual pathway, the optic nerve and the retina using the glymphatic system

Rajendran

Chidambaram

Srikanth

et al. 2022

Preprint

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The blood neural barriers are formidable barriers that prevent delivery of drugs into the eye and the brain. Currently, large biologics are used for treating many diseases of the eye and the brain. But the blood retinal barrier and the blood brain barrier prevent entry of these useful drugs into the eye and the brain respectively. Hence, there is a need for a drug delivery technique to bypass these natural barriers. Bevacizumab (Avastin) is a full length humanized monoclonal antibody with a molecular weight of 149kda. It binds to circulating vascular endothelial growth factor A and prevents interaction with vascular endothelial growth receptors. This results in blocking endothelial response and tumor vascularization. Bevacizumab is used to prevent choroidal neovascularization in age related macular degeneration and to prevent retinal neovascularization in diabetic retinopathy. It is also used for treating certain types of brain cancer. But it crosses neither the blood retinal barrier nor the blood brain barrier. This in vivo mouse study assessed the delivery of a commercial formulation of bevacizumab into the retina of mice using different ocular techniques like topical drops, subconjunctival injection, intravitreal injection and a novel maxillofacial technique. The objective was to assess whether the novel maxillofacial drug delivery technique could deliver drugs into the retina and to compare the efficacy of the maxillofacial technique with the mentioned ocular techniques. The distribution of bevacizumab was further compared with retinoschisin which is a small protein with a molecular weight of 24kda. Intravitreal injection and maxillofacial technique were effective in delivering drugs into the retina. In addition, the maxillofacial technique could target the brain including regions involved in the visual pathway and the optic nerve. The glymphatic pathway could also be targeted for drug delivery. Drug was also detected in the contralateral optic nerve and retina. Based on our study findings, we propose a new concept to explain the presence of the drug in the contralateral eye. We propose that after maxillofacial drug delivery, early distribution of the drug can occur in the CSF at the optic chiasma from the brain via the glymphatic system. In the case of the intravitreal injection, the drug from the experimental eye may be cleared through the glymphatic pathway of the ipsilateral optic nerve into the CSF surrounding the nerve. The crossover of the ipsilateral optic nerve fibers at the optic chiasma can result in further distribution of the drug in the CSF at the optic chiasma. From the region of the optic chiasma, the drug can distribute into the CSF surrounding the contralateral optic nerve. The drug can be then distributed into the contralateral optic nerve through the glymphatic pathway and be delivered into the contralateral eye. The drug can be further cleared into the aqueous of the contralateral eye through the anterior clearance pathway.

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Section: Discussionmentioning

confidence: 99%

A novel maxillofacial technique to deliver drugs to the visual pathway, the optic nerve and the retina using the glymphatic system

Rajendran

Chidambaram

Srikanth

et al. 2022

Preprint

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“…Other less studied pathological mechanisms likely to be involved in the optic neuropathy or secondary glaucoma after vitreoretinal surgery could be related to newly discovered glymphatic system (Wostyn et al. 2015; Wostyn 2021). Post‐vitrectomy, the rapid changes of IOP and composition of the vitreous substitute (whether gas or SO) as well as changes in cerebrospinal fluid surrounding the optic nerve could have impact on the pathogenesis of glaucoma.…”

Section: Discussionmentioning

confidence: 99%

Risk of glaucoma after vitreoretinal surgery – Findings from a population‐based cohort study

Loukovaara

Gucciardo

Korhonen

et al. 2022

Acta Ophthalmologica

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Purpose To investigate the association between different types of vitrectomy and risk of different types of glaucoma and to determine the effect of systemic medication and diabetes status on this risk. Methods A population‐based nested case–control study included individuals of age ≥ 18 years who had undergone single vitrectomy, vitrectomy with retinal procedure, or combined phaco‐vitrectomy between 2001 and 2010. End of follow‐up was 2017. Odds ratio (OR) for the development of glaucoma after different types of vitrectomy and 95% confidence interval (CI) were based on conditional logistic regression models. For every glaucoma case, five controls were matched by age, sex, start of follow‐up year, and hospital district. Results The cohort (n = 37 687), of which 52.8% was female, consisted of 6552 individuals diagnosed with glaucoma and 31 135 controls matched by age, sex, and hospital district. Vitrectomy was performed on 103 eyes in the glaucoma group and 158 eyes in the control group. As regards the risk of any glaucoma, the risk was lowest in eyes that underwent combined phaco‐vitrectomy (OR: 2.7, 95% CI: 1.8–4.1), followed by single vitrectomy (OR: 3.15, 95% CI: 2.1–4.8), and highest in eyes that underwent vitrectomy with retinal procedure (OR: 4.5, 95% CI: 2.7–7.4). Diabetes had no effect (OR: 0.96, 95% CI: 0.92–1.01), but 5‐year systemic statin use slightly decreased glaucoma risk (OR: 0.86, 95% CI: 0.77–0.97). Conclusions Vitreoretinal surgery was associated with an increased glaucoma risk; the risk being related to the complexity of vitrectomy. Long‐term systemic statin therapy may decrease glaucoma risk, while diabetes had no association.

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“…Of note, the resulting astrogliosis is a process associated with abnormalities of Aquaporin-4, also known as AQP-4, which is an encoded water channel protein, leading to disturbances of the glymphatic flow [122,123] which plays a crucial role in the removal of debris (including amyloid β (Aβ) and tau aggregates) across the neuronal interstitial space [124]. Interestingly, AQP4 abnormalities have been observed in tau-induced neurodegeneration [124], including glaucoma [125].…”

Section: Oxidative Damage Is a Common Feature In Both Glaucoma And Ta...mentioning

confidence: 99%

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

Passaro,

Matarazzo,

Abbadessa

et al. 2023

JCM

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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.

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Do normal-tension and high-tension glaucoma result from brain and ocular glymphatic system disturbances, respectively?

Cited by 9 publications

References 7 publications

A novel maxillofacial technique to deliver drugs to the visual pathway, the optic nerve and the retina using the glymphatic system

A novel maxillofacial technique to deliver drugs to the visual pathway, the optic nerve and the retina using the glymphatic system

Risk of glaucoma after vitreoretinal surgery – Findings from a population‐based cohort study

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

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