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

Agarwal, Renu; Agarwal, Puneet; Iezhitsa, Igor

doi:10.1080/17460441.2023.2246892

Cited by 4 publications

(3 citation statements)

References 101 publications

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“…Various animal species have been employed to simulate disease-like conditions and study their effects. To understand the complex glaucoma pathology and to analyze novel treatments, different glaucoma models are currently employed [25,26]. As in other fields of medical research, rodents are mainly used for in vivo studies.…”

Section: Glaucoma Animal Modelsmentioning

confidence: 99%

Glaucoma Animal Models beyond Chronic IOP Increase

Tsai,

Reinehr,

Deppe

et al. 2024

IJMS

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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.

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Section: Glaucoma Animal Modelsmentioning

confidence: 99%

Glaucoma Animal Models beyond Chronic IOP Increase

Tsai,

Reinehr,

Deppe

et al. 2024

IJMS

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“…Many animal models have been developed, characterized, and utilized to study the pathogenic elements of OHT and glaucoma [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ] ( Table 2 ). We chose to use the mouse in the present study.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, ≥30% of patients do not respond well to drug therapy, especially FP receptor agonists [1,16,17]. Uncontrolled elevated IOP and IOP spikes may even re- Many animal models have been developed, characterized, and utilized to study the pathogenic elements of OHT and glaucoma [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] (Table 2). We chose to use the mouse in the present study.…”

Section: Introductionmentioning

confidence: 99%

Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists

Sharif,

Millar,

Zode

et al. 2024

IJMS

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We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all compounds significantly (p < 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 µg/dose) over three weeks, the time course and magnitude of the responses varied. The onset of action of NS-304 (IP-PG receptor agonist) and rivenprost (EP4-PG receptor agonist) was slower than that of misoprostol (mixed EP2/EP3/EP4-PG receptor agonist), PF-04217329 (EP2-PG receptor agonist), and butaprost (EP2-PG receptor agonist). The rank order of IOP-lowering efficacies aligned with the onset of actions of these compounds. Peak IOP reductions relative to vehicle controls were as follows: misoprostol (74.52%) = PF-04217329 (74.32%) > butaprost (65.2%) > rivenprost (58.4%) > NS-304 (55.3%). A literature survey indicated that few previously evaluated compounds (e.g., latanoprost, timolol, pilocarpine, brimonidine, dorzolamide, cromakalim analog (CKLP1), losartan, tissue plasminogen activator, trans-resveratrol, sodium 4-phenyl acetic acid, etc.) in various animal models of steroid-induced OHT were able to match the effectiveness of misoprostol, PF-04217329 or butaprost. Since a common feature of the latter compounds is their relatively high affinity and potency at the EP2-PG receptor sub-type, which activates the production of intracellular cAMP in target cells, our studies suggest that drugs selective for the EP2-PG receptor may be suited to treat corticosteroid-induced OHT.

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