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Review
. 2024 Jan 11;25(2):906.
doi: 10.3390/ijms25020906.

Glaucoma Animal Models beyond Chronic IOP Increase

Teresa Tsai  1 , Sabrina Reinehr  1 , Leonie Deppe  1 , Alexandra Strubbe  1 , Nils Kluge  1 , H Burkhard Dick  1 , Stephanie C Joachim  1
Affiliations
Review

Glaucoma Animal Models beyond Chronic IOP Increase

Teresa Tsai et al. Int J Mol Sci. .

Abstract

Glaucoma is a complex and multifactorial disease defined as the loss of retinal ganglion cells (RGCs) and their axons. Besides an elevated intraocular pressure (IOP), other mechanisms play a pivotal role in glaucoma onset and progression. For example, it is known that excitotoxicity, immunological alterations, ischemia, and oxidative stress contribute to the neurodegeneration in glaucoma disease. To study these effects and to discover novel therapeutic approaches, appropriate animal models are needed. In this review, we focus on various glaucoma animal models beyond an elevated IOP. We introduce genetically modified mice, e.g., the optineurin E50K knock-in or the glutamate aspartate transporter (GLAST)-deficient mouse. Excitotoxicity can be mimicked by injecting the glutamate analogue N-methyl-D-aspartate intravitreally, which leads to rapid RGC degeneration. To explore the contribution of the immune system, the experimental autoimmune glaucoma model can serve as a useful tool. Here, immunization with antigens led to glaucoma-like damage. The ischemic mechanism can be mimicked by inducing a high IOP for a certain amount of time in rodents, followed by reperfusion. Thereby, damage to the retina and the optic nerve occurs rapidly after ischemia/reperfusion. Lastly, we discuss the importance of optic nerve crush models as model systems for normal-tension glaucoma. In summary, various glaucoma models beyond IOP increase can be utilized.

Keywords: animal model; autoimmune glaucoma; excitotoxicity; glaucoma; ischemia–reperfusion; nerve crush; normal-tension glaucoma.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Model systems and induction methods to create glaucoma animal models without chronic IOP elevation. Zebrafish, rodents such as mice and rats, and porcine organ cultures can be used to simulate glaucoma-like damage. To induce glaucoma-like damage in porcine organ cultures of the eye (red box), different excitotoxicity-based substances can be used. In zebrafish, in addition to the excitotoxicity-based substances, genetic modulations can also be carried out to create an NTG model. In rodents, the opportunities range from excitotoxicity-based substances, genetic and immunomodulatory modifications, as well as ischemia/reperfusion induction to optic nerve crush.
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