Use of Animal Models and Techniques in Glaucoma Research: Introduction

Quigley, Harry A.

doi:10.1007/978-1-4939-7407-8_1

Cited by 18 publications

(11 citation statements)

References 39 publications

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“…However, it is possible to select animals with limited anterior damage. Finally, as mentioned in a recent review of glaucoma animal models 38 , rodents have only a glial lamina rather than a structured lamina cribrosa. Thus, humans or primates may exhibit a different pathology of axon damage and pattern of progression.…”

Section: Discussionmentioning

confidence: 97%

Development and characterization of a new rat ocular hypertension model induced by intracameral injection of conjunctival fibroblasts

Nakagawa

Sakai

Tokushige

et al. 2019

Sci Rep

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Glaucoma is a chronic optic neuropathy that leads to visual field loss. Elucidating the mechanisms underlying glaucoma is essential for developing new treatments, such as neuroprotective drugs. Various glaucoma models based on the induction of intraocular pressure (IOP) elevation have been established for use in glaucoma studies. However, the time-dependent pathological changes accompanying IOP elevation have not been fully elucidated. In this study, rat conjunctival fibroblasts were injected into the anterior chamber of rat eyes, and IOP elevation was induced for 28 days. Glaucomatous signs such as optic nerve head cupping, retinal thinning, glial activation and apoptotic signaling in the retina were obvious in the cell-injected eyes on the 14th day after injection. The pattern of retinal ganglion cell (RGC) loss differed by the magnitude of IOP elevation. The number of RGCs decreased by 37.5% in eyes with IOP lower than 50 mmHg (Under-50) and by 88.0% in those with IOP higher than 50 mmHg (Over-50) 28 days after cell injection. The RGC counts were correlated with IOP in the Under-50 group but not in the Over-50 group. Our model may contribute to the investigation of pathogenic mechanisms of glaucoma and the development of new glaucoma treatments.

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Section: Discussionmentioning

confidence: 97%

Development and characterization of a new rat ocular hypertension model induced by intracameral injection of conjunctival fibroblasts

Nakagawa

Sakai

Tokushige

et al. 2019

Sci Rep

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“…Glaucoma is a progressive optic neuropathy that is accompanied by the excavation of the optic nerve head and a loss of visual sensitivity in the sequence beginning in the mid-peripheral visual field. Types of glaucoma are classified as open-angle, angle-closure, glaucoma due to another disease, and childhood onset glaucoma [55,56]. It is worth noting that the leading cause of irreversible blindness worldwide is glaucoma.…”

Section: Ocular Conditionsmentioning

confidence: 99%

Penetration Enhancers in Ocular Drug Delivery

Moiseev

Morrison

Steele³

et al. 2019

Pharmaceutics

152

124

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There are more than 100 recognized disorders of the eye. This makes the development of advanced ocular formulations an important topic in pharmaceutical science. One of the ways to improve drug delivery to the eye is the use of penetration enhancers. These are defined as compounds capable of enhancing drug permeability across ocular membranes. This review paper provides an overview of anatomical and physiological features of the eye and discusses some common ophthalmological conditions and permeability of ocular membranes. The review also presents the analysis of literature on the use of penetration-enhancing compounds (cyclodextrins, chelating agents, crown ethers, bile acids and bile salts, cell-penetrating peptides, and other amphiphilic compounds) in ocular drug delivery, describing their properties and modes of action.

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“…Currently, the lack of experimental standardization for glaucoma study neither for in vitro nor for animal models (e.g., design, sample size, analytical techniques, statistics, reproducibility, lack of specific species, and so on) has partly compromised the proper identification of glaucoma biomarkers. Previous in vitro studies on TM have undoubtedly helped to understand the molecular changes in TM following OS treatment; however, most of the clinical trial results based on small animal models (i.e., rodents) revealed their translational failure mainly due to the different degree of similarity between human disease and the animal model used ( 21 , 26 , 92 – 94 ).…”

Section: Conclusion and Future Prospectsmentioning

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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Use of Animal Models and Techniques in Glaucoma Research: Introduction

Cited by 18 publications

References 39 publications

Development and characterization of a new rat ocular hypertension model induced by intracameral injection of conjunctival fibroblasts

Development and characterization of a new rat ocular hypertension model induced by intracameral injection of conjunctival fibroblasts

Penetration Enhancers in Ocular Drug Delivery

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

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