. 2010 Mar 10;2:21–37. doi: 10.2147/eb.s9363

Table 2.

Animal models of mitochondrial optic neuropathy

Model and reference	Eells et al¹⁰⁷	Zhang et al⁴⁹ (mice), Hayworth et al⁵⁰ (transgenic mice) Rojas et al⁵² (rats)	Qi et al⁸³	Qi et al⁸⁴	Qi et al²⁷	Ellouze et al¹⁰⁸
Mechanism	Chemical inhibition of cytochrome oxidase	Chemical inhibition of complex I	Translational suppression of SOD	Translational suppression of nuclear-encoded complex I subunit	Allotropic expression of mutant complex I subunit	Allotropic expression of mutant complex I subunit
Method	Systemic methanol intoxication and nitrous oxide exposure	Intravitreal rotenone	Intravitreal rAAV-delivered SOD2 ribozyme	Intravitreal rAAV-delivered NDUFA1 ribozyme	Intravitreal rAAV-delivered nuclear 11778 ND4 mutant	Intravitreal injection of optimized mutant 11778 ND4 fusion gene with electroporation
Species	Rats	Rats and mice	Mice	Mice	Mice	Rats
Earliest change reported	ERG abnormalities (24 hr)	IPL edema (30 min)	Optic disc edema (6 weeks)	Optic disc edema (4 months)	Optic disc edema (1 month)	GCL degeneration (25 days)
Late structural effects	Major photoreceptor + optic nerve degeneration	GCL + RNFL + axonal + optic nerve degeneration	GCL + optic nerve degeneration; demyelination	GCL degeneration; demyelination	GCL + optic nerve degeneration	GCL and axonal degeneration
Late functional effects	Prolonged latency and attenuation of FEPs and ERG elimination	Decreased illuminance sensitivity threshold	N/A	N/A	N/A	Decreased spatial contrast sensitivity
Reported neurochemical changes	Decreased mitochondrial metabolites and glutathione	Decreased retinal metabolic capacity; increased superoxide and apoptosis	N/A	N/A	GCL + optic nerve oxidative stress	N/A
Highlights	Resemblance to methanol intoxication in humans; modeling of reversible damage is possible	Efficient as a drug-screening tool; allows behavioral assessment; features specific ganglion cell markers in transgenic mice	Allows the study of oxidative stress independent of ETC dysfunction	Allows to study the role of nuclear-encoded mitochondrial proteins in neurodegeneration	Mechanistic resemblance to LHON	Mechanistic resemblance to LHON, features specific ganglion cell markers
Disadvantages	Systemic methanol and nitrous oxide interfere with behavioral assessment of visual function	Causal role of environmental toxins in neurodegeneration not demonstrated	Damage not severe enough to explain visual deficits; difficult behavioral assessment of visual function	Damage not severe enough to explain visual deficits; difficult behavioral assessment of visual function; no human counterpart	Uncertain integration of mutant nuclear protein to complex I; difficult behavioral assessment of visual function	Technically demanding

Abbreviations: ERG, electroretinogram; ETC, electron transport chain; FEP, flash-evoked potentials; IPL, inner plexiform layer; LHON, Leber’s hereditary optic neuropathy; NDUFA1, NADH dehydrogenase 1 alpha subcomplex; GCL, ganglion cell layer; RNFL, retinal nerve fiber layer; rAAV, adenovirus-associated vector; SOD, superoxide dismutase.