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In recent years, chromatic pupillometry is used in humans to evaluate the activity of melanopsin expressing intrinsic photosensitive retinal ganglion cells (ipRGCs). Blue light is used to stimulate the ipRGCs and red light activates the rod/cone photoreceptors. The late re-dilation phase of pupillary light reflex is primarily driven by the ipRGCs. Optic neuropathies i.e. Leber hereditary optic neuropathy (LHON), autosomal dominant optic atrophy (ADOA), nonarteritic anterior ischemic optic neuropathy (NAION), glaucoma, optic neuritis and idiopathic intracranial hypertension (IIH) are among the diseases, which have been subject to pupillometric studies. The ipRGCs are differentially affected in these various optic neuropathies. In mitochondrial optic neuropathies, the ipRGCs are protected against degeneration, whereas in glaucoma, NAION, optic neuritis and IIH the ipRGCs are damaged. Here, we will review the results of pupillometric, histopathological and animal studies evaluating the ipRGCs in mitochondrial and non-mitochondrial optic neuropathies.

Mitochondrial impairment in ocular disease pathogenesis has been well recognised since the first disease-linked mitochondrial DNA mutation was described for Leber’s Hereditary Optic Neuropathy in 1988. Our increased understanding of mitochondrial function and dynamics since then has suggested that mitochondrial dysfunction may be a key underlying factor contributing to retinal ganglion cell loss in a range of optic neuropathies. Mitochondrial dysfunction is traditionally attributed to heritable nuclear and mitochondrial DNA mutations but may be exacerbated by aging, oxidative stress and environmental factors. Mitochondrial impairment limits endogenous energy production and sensitises cells to stress and injury. Understanding how impairment of this key organelle can lead to loss of specific neuronal populations provides possibilities for neuroprotective intervention to prevent retinal ganglion cell degeneration. To address mechanisms of disease pathogenesis associated with vision loss we performed a detailed analysis of mitochondrial function using human cell lines from Autosomal Dominant Optic Atrophy family pedigrees bearing an identical mutation of the OPA1 gene. These patients may suffer specific loss of retinal ganglion cells, but the disease phenotype varies dramatically within family pedigrees. We compared patients with severe vision loss and patients with relatively preserved vision and found a clear defect in mitochondrial energy production and respiration in patients with poor vision. In Autosomal Dominant Optic Atrophy patients with normal vision numerous components of oxidative phosphorylation were increased. These data suggest that OPA1 deficiency impairs oxidative phosphorylation efficiency, but compensation through increases in the distal complexes of the respiratory chain may preserve mitochondrial energy production in patients who maintain normal vision. Evaluation of in vivo retinal mitochondrial function provides insight into early events occurring