Table 1.

Overview of glaucoma animal models without chronic IOP elevation. Outcomes, advantages, and challenges for these models are listed.

Models		Outcomes	Advantages	Challenges	References
Genetic normal-tension glaucoma models	E50K	Increased apoptosis rate RGC loss Reduction of the retinal thickness	No further intervention necessary	Patients represent approximately 10% of cases worldwide Unclear how this specific degeneration is caused	[50,53,54]
	GLAST, EAAC1	Cupping of the optic nerve head Degeneration of axons GLAST: 8 months EAAC1: 8 weeks	No further interventions necessary	GLAST: long time frame Degeneration is not only focused on a specific area	[69,73,75]
Excitotoxicity-based glaucoma models	NMDA	Rapid degeneration of RGCs after one day Optic nerve degeneration	Usable in ex vivo models	Intravitreal injections	[87,97,101]
Immune-based glaucoma models	EAGs (HSPs, S100B, ONA)	RGC loss Caspase-mediated apoptosis Degeneration of optic nerve Microglia activation	To analyze immune system as an important risk factor	Immunization of animals	[115,118,121]
Ischemia models	Increased IOP, chronic carotid occlusion, transient obstruction of retinal/cerebral artery, vasoconstriction of retinal vessels	Oxidative stress (ROS) Severe neuronal damage (retina and optic nerve) Impaired retinal function Gliosis	Reproducibility Possibility of longitudinal follow-up (OCT, ERG)	Surgical intervention Surgical skills Long anesthesia time	[21,138,147]
Optic nerve crush or transection models		Retrograde degeneration of RGCs Comparable death of RGCs and axons Majority of RGCs die by apoptosis	Reproducibility Labeling of regenerating axons	Surgical intervention Surgical skills	[160,163,168]