Experimental Models of Glaucoma: A Powerful Translational Tool for the Future Development of New Therapies for Glaucoma in Humans—A Review of the Literature

Evangelho, Karine; Mastronardi, Claudio A.; de-la-Torre, Alejandra

doi:10.3390/medicina55060280

Cited by 42 publications

(49 citation statements)

References 90 publications

(159 reference statements)

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“…In contrast, in clinical trials investigators are able to control a part of participants’ behaviour. Additionally, metabolism and aging of animals and supplemented doses of antioxidants differ from the human being context [ 10 , 11 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

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Glaucoma and Antioxidants: Review and Update

et al. 2020

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Glaucoma is a neurodegenerative disease characterised by the progressive degeneration of retinal ganglion cells. Oxidative stress has been related to the cell death in this disease. Theoretically, this deleterious consequence can be reduced by antioxidants substances. The aim of this review is to assemble the studies published in relation to antioxidant supplementation and its effects on glaucoma and to offer the reader an update on this field. With this purpose, we have included studies in animal models of glaucoma and clinical trials. Although there are variable results, supplementation with antioxidants in glaucoma may be a promising therapy in glaucoma.

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Section: Discussionmentioning

confidence: 99%

“…However, in this context other animal models have also been considered. Animal model of glaucoma have been extensively described elsewhere [10,11].…”

Section: Introductionmentioning

confidence: 99%

Glaucoma and Antioxidants: Review and Update

et al. 2020

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“…Several animal models of glaucoma have been used to characterise the expression of NADPH oxidase in the pathogenesis of glaucoma. The animal models utilise different techniques to mimic various pathological processes in glaucoma, such as retinal ischemia and reperfusion, ocular hypertension, and optic nerve crush injury, to mimic pathological features of glaucoma [ 96 ]. Some features, including microglial activation and neuronal injury in the retina, and neuronal cell death due to apoptosis of RGC in glaucoma, can lead to vision impairment [ 97 ].…”

Section: Expression Of Nadph Oxidase and Glaucoma Pathologymentioning

confidence: 99%

“…Ocular hypertension in animals is induced by either applying laser photocoagulation to the trabecular meshwork or cauterizing the episcleral vein [ 96 ]. NOX2 has been found to co-localise with activated microglia in the ONHs from mice after laser photocoagulation of the trabecular meshwork [ 73 ].…”

Section: Expression Of Nadph Oxidase and Glaucoma Pathologymentioning

confidence: 99%

Oxidative Stress and the Role of NADPH Oxidase in Glaucoma

2021

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Glaucoma is characterised by loss of retinal ganglion cells, and their axons and many pathophysiological processes are postulated to be involved. It is increasingly understood that not one pathway underlies glaucoma aetiology, but rather they occur as a continuum that ultimately results in the apoptosis of retinal ganglion cells. Oxidative stress is recognised as an important mechanism of cell death in many neurodegenerative diseases, including glaucoma. NADPH oxidase (NOX) are enzymes that are widely expressed in vascular and non-vascular cells, and they are unique in that they primarily produce reactive oxygen species (ROS). There is mounting evidence that NOX are an important source of ROS and oxidative stress in glaucoma and other retinal diseases. This review aims to provide a perspective on the complex role of oxidative stress in glaucoma, in particular how NOX expression may influence glaucoma pathogenesis as illustrated by different experimental models of glaucoma and highlights potential therapeutic targets that may offer a novel treatment option to glaucoma patients.

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“…The proper measures to use animals of different ages as experimental models include a careful use of anesthetic agents as well as the attention for both physical decay and stress conditions ( 31 ).…”

Section: Introductionmentioning

confidence: 99%

A 3D Model of Human Trabecular Meshwork for the Research Study of Glaucoma

et al. 2020

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Glaucoma is a multifactorial syndrome in which the development of pro-apoptotic signals are the causes for retinal ganglion cell (RGC) loss. Most of the research progress in the glaucoma field have been based on experimentally inducible glaucoma animal models, which provided results about RGC loss after either the crash of the optic nerve or IOP elevation. In addition, there are genetically modified mouse models (DBA/2J), which make the study of hereditary forms of glaucoma possible. However, these approaches have not been able to identify all the molecular mechanisms characterizing glaucoma, possibly due to the disadvantages and limits related to the use of animals. In fact, the results obtained with small animals (i.e., rodents), which are the most commonly used, are often not aligned with human conditions due to their low degree of similarity with the human eye anatomy. Although the results obtained from non-human primates are in line with human conditions, they are little used for the study of glaucoma and its outcomes at cellular level due to their costs and their poor ease of handling. In this regard, according to at least two of the 3Rs principles, there is a need for reliable human-based in vitro models to better clarify the mechanisms involved in disease progression, and possibly to broaden the scope of the results so far obtained with animal models. The proper selection of an in vitro model with a “closer to in vivo” microenvironment and structure, for instance, allows for the identification of the biomarkers involved in the early stages of glaucoma and contributes to the development of new therapeutic approaches. This review summarizes the most recent findings in the glaucoma field through the use of human two- and three-dimensional cultures. In particular, it focuses on the role of the scaffold and the use of bioreactors in preserving the physiological relevance of in vivo conditions of the human trabecular meshwork cells in three-dimensional cultures. Moreover, data from these studies also highlight the pivotal role of oxidative stress in promoting the production of trabecular meshwork-derived pro-apoptotic signals, which are one of the first marks of trabecular meshwork damage. The resulting loss of barrier function, increase of intraocular pressure, as well the promotion of neuroinflammation and neurodegeneration are listed as the main features of glaucoma. Therefore, a better understanding of the first molecular events, which trigger the glaucoma cascade, allows the identification of new targets for an early neuroprotective therapeutic approach.

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Experimental Models of Glaucoma: A Powerful Translational Tool for the Future Development of New Therapies for Glaucoma in Humans—A Review of the Literature

Cited by 42 publications

References 90 publications

Glaucoma and Antioxidants: Review and Update

Glaucoma and Antioxidants: Review and Update

Oxidative Stress and the Role of NADPH Oxidase in Glaucoma

A 3D Model of Human Trabecular Meshwork for the Research Study of Glaucoma

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