Exploring the current use of animal models in glaucoma drug discovery: where are we in 2023?

ABSTRACT

Introduction

Animal models are widely used in glaucoma-related research. Since the elevated intraocular pressure (IOP) is a major risk factor underlying the disease pathogenesis, animal models with high IOP are commonly used. However, models are also used to represent the clinical context of glaucomatous changes developing despite a normal IOP.

Areas Covered

Herein, the authors discuss the various factors that contribute to the quality of studies using animal models based on the evaluation of studies published in 2022. The factors affecting the quality of studies using animal models, such as the animal species, age, and sex, are discussed, along with various methods and outcomes of studies involving different animal models of glaucoma.

Expert opinion

Translating animal research data to clinical applications remains challenging. Our observations in this review clearly indicate that many studies lack scientific robustness not only in their experiment conduct but also in data analysis, interpretation, and presentation. In this context, ensuring the internal validity of animal studies is the first step in quality assurance. External validity, however, is more challenging, and steps should be taken to satisfy external validity at least to some extent.

KEYWORDS:

• Glaucoma
• animal models
• intraocular pressure
• retinal ganglion cells
• optic neuropathy

Article highlights

• The majority of glaucoma research utilizes animal models with high IOP, and the most commonly used method involves intracameral injection of microbeads.

• Optic neuropathy models involving optic nerve crush in animals are commonly utilized to mimic glaucomatous changes developing despite normal IOP.

• Both types of animal models represent clinically relevant endophenotypes of glaucoma.

• The multifactorial pathogenesis of glaucoma, however, makes it difficult to precisely replicate the disease in animals.

• More human-relevant approaches such as the generation of human induced pluripotent stem cells, micro-physiological systems and human organoids may have an advantage over use of a variety of animal studies.

• Undertaking enhanced measures to ensure the internal and external validity of animal studies will increase their translational value for glaucoma drug discovery.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors acknowledge financial support by the International Medical University, Kuala Lumpur, Malaysia under grant no. MMHS I-2023(01) and the Ministry of Higher Education of the Government of Malaysia, under grant no. [FRGS/1/2020/SKK0/IMU/01/1].