Table 1.
Comparative features of Leber’s hereditary optic neuropathy and the animal model of rotenone-induced optic neuropathy
| Leber’s hereditary optic neuropathy | Rotenone-induced optic neuropathy | |
|---|---|---|
| Course | • Acute to subacute onset (weeks to months) • Permanent damage in the majority of cases |
• Rapid onset of neurodegeneration (hours to days) • Permanent damage |
| Etiology | • mDNA mutations | • Rotenone |
| Mechanism | • Abnormal expression of transmembrane (ND1, ND4 and ND6) complex I subunits | • Blocks entry of ubiquinone into ramp connecting the transmembrane (ND1, ND4 and ND6) and peripheral sectors of complex I |
| Oxidative stress | • Increased blood oxidative stress • Increased leukocyte DNA oxidative damage • Increase in oxidative stress-induced lymphocyte apoptosis |
• Increased superoxide production confined to ganglion cell layer (GCL) |
| Metabolic impairment and excitotoxicity | • Intracellular calcium inclusions • Swollen mitochondria and ganglion cells • Decreased complex I activity and oxidative phosphorylation • Decreased NADH/NAD ratio |
• Early increased metabolic capacity • Late decreased metabolic capacity • Neurodegenerative effects prevented by NMDA receptor blockade |
| Early structural effects | • RNFL edema | • IPL edema |
| Late structural effects | • Selective and massive degeneration of the RNFL and GCL • 95%–100% atrophy of papillomacular bundle • GCL pyknosis • Optic nerve atrophy, gliosis and demyelination • Mild IPL atrophy |
• Selective and massive degeneration of the RNFL and GCL • 50% atrophy of peripapillary fibers • GCL apoptosis • Optic nerve atrophy and gliosis • IPL atrophy |
| Functional deficits | • Decreased visual acuity, dyschromatopsia and contrast sensitivity • Preserved pupillary light reflex • Transynaptic structural evidence of retinal deafferentiation |
• Decreased contrast sensitivity • Preserved pupillary light reflex • Transynaptic metabolic evidence of retinal deafferentiation • Visual deficits highly correlate with structural damage |
Abbreviations: DNA, deoxyribonucleic acid; IPL, inner plexiform layer; GCL, ganglion cell layer; RNFL, retinal nerve fiber layer.