Previous research has reported that nerve regeneration and visual function recovery are impossible following retinal ganglion cells and optic nerve injury. However, recent studies have described many factors that can promote or inhibit axon regeneration. Currently, several factors are shown to contribute to optic nerve regeneration under specific conditions: for example, blockade of regeneration inhibitory factors is reported to act synergistically with overexpression of regeneration stimulating factors. These findings may facilitate the establishment of novel therapeutic strategies for treatment of optic nerve injury and glaucoma

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　Leber hereditary optic neuropathy（LHON）is a maternally inherited optic neuropathy caused by point mutations in the mitochondrial gene. It is speculated that genetically mutated retinal ganglion cells are central to the pathogenesis of LHON; but some external factors may also be in volved in the onset of this disease. Clinical studies have shown that LHON is caused by a wide range of factors, including smoking or heavy alcohol consumption. However, the behavior of reti nal ganglion cells post exposure to external factors remains unknown.

　Although animal models are commonly used for basic research on retinal tissue, it is difficult to accurately reflect cellular behavior in pathological studies owing to the differences between ani

mal and human tissues. Induced pluripotent stem（iPS）cells can be used to differentiate retinal ganglion cells from human iPS cells to obtain human tissue, increasing the possibility of observ ing cell behavior similar to actual pathological conditions.

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　We generated retinal ganglion cells from human/murine induced pluripotent stem cells（iPSCs）and embryonic stem cells（ESCs）, which allowed us to investigate optic nerve diseases in vitro. While hereditary diseases are investigated with human disease-specific iPSCs-RGC generated from patient cells, non-hereditary diseases, including ischemic optic neuropathy, glaucoma and trauma, are investigated with human iPSCs/ESCs-RGC upon the application of stress, hypoxia, high pressure, and extensional force. An in vitro evaluation system for chemical agents is used for drug discovery that includes neuro-protective and neuro-regenerative drugs. RGC and axon development are also investigated using molecular biology techniques. RGCs survive in the retina when injected into the vitreous cavity of mice, which suggests the possibility of RGC transplantation. Thus, RGCs generated from iPSCs/ESCs contribute translational research for optic nerve diseases.

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　We examined the pupillary light reflex in 19 individuals to determine the role of intrinsically photosensitive retinal ganglion cells（ipRGCs）in light-induced discomfort associated with migraine. This was performed using blue light（470 nm）and red light（635 nm）. The study participants included eight patients with migraine（migraine group: three with aura, and five without aura）and 11 healthy volunteers（control group）. The participants underwent 10 minutes of dark adaptation, after which they were exposed to both red and blue lights emitted at an illuminance of 100 cd/m². This was performed randomly at 1second intervals. The light reflex was recorded for a total of 10 seconds until mydriasis was observed. The average constriction rates（CRs）to blue light were 46.3 ± 6.2％, and 40.0 ± 4.6% for migraine and control groups, respectively（p=0.03）. The migraine group had significantly higher CRs than the control group. No significant differences in CRs were noted between the groups with respect to red light. A+2 is the time required to change half of the changing pupil diameter. The t2 in the migraine group was 316.7 ± 58.3 msec for red light and 304.2 ± 43.1 msec for blue light. The t2 in the control group was 378.8 ± 31.9 msec for red light and 353.0 ± 38.8 msec for blue light. The migraine group had a significantly shorter t2 compared with that in the control group for both red and blue light. Significant constriction was observed in patients when subjected to blue light, which is the optimal wavelength range for ipRGCs. These findings suggest that exposure to blue light, but not red light, may cause light-induced discomfort associated with migraines.

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　We herein describe the clinical outcome of a patient with bilateral optic neuropathy and positive anti-retinal antibodies. A 48-year-old man suffering from visual impairment in both eyes was referred to our hospital. His best-corrected visual acuity was light perception for OD and 0.07 for OS, and the critical flicker fusion frequency was untestable for OD and 15 Hz for OS. Fundoscopy revealed pallor in the right optic disc and swelling in the left optic disc. Electroretinogram amplitude was slightly decreased in both eyes, whereas enhanced orbital MRI showed no abnormalities in bilateral optic nerves. Furthermore, systemic examination indicated no malignancy. Although the cause of his bilateral optic neuropathy was unknown, western blotting using patient serum and rat retinal extract revealed 100 kD and 150 kD bands, respectively. In addition, immunostaining of rat retina with patient serum displayed staining of the retinal ganglion cell layer. The patient was ultimately diagnosed to have autoimmune retinopathy due to the presence of retinal autoimmune antibodies. Generally, autoimmune retinopathy is characterized by photoreceptor dysfunction. However, this patient showed optic atrophy and immunostaining of the retinal ganglion cell layer, suggesting a different pathogenesis from that typical noted.

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Introduction and Objective: This study aimed to compare the characteristics and treatment outcomes of neuromyelitis optica spectrum disorder（NMOSD）with those of typical and atypical optic neuritis（ON）at JEC Eye Hospitals in Kedoya and Menteng from 2017 to 2021.

Methods: This retrospective, descriptive study used the medical record date of patients treated with high-dose intravenous methylprednisolone at JEC Eye Hospitals. The diagnosis was made based on the Optic Neuritis Treatment Trial and International Consensus NMOSD diagnostic criteria（2015）and categorized as typical or atypical ON and NMOSD, respectively. Demographic, clinical, and radiological features and optical coherence tomography features were evaluated. The best-corrected visual acuity（BCVA）, Humphrey visual field examination, optic nerve head retinal nerve fiber layer（RNFL）thickness and macular ganglion cell complex（GCC）thickness were analyzed before and after treatment.

Result: In total, 64 patients（78 eyes）were included—43 patients（43 eyes）with typical ON, 14 patients（24 eyes）with atypical ON, and seven patients（11 eyes）with NMOSD. Most patients were women with a sudden onset of blurred vision and retrobulbar features. Older age, bilaterality, and recurrence were significantly associated with NMOSD compared to other conditions. The NMOSD and typical ON groups were more likely to present with retrobulbar ON than other groups. Long-segment optic nerve enhancement on neuroimaging was observed in all patients with NMOSD. Eyes with NMOSD had significantly lower nadir BCVA than those typical and atypical ON, with 81.78% showing nadir BCVA＜0.1. After treatment, all groups showed significant improvement in BCVA; however, the difference among the groups was not significant. Initially, the NMOSD group showed significantly lower inferior RNFL thickness than the other groups. However, the NMOSD group showed lesser thinning of the mean RNFL and GCC thickness than the other groups.

Conclusion: Bilateral involvement and recurrence of attack combined with distinctive neuroimaging features should raise awareness for NMOSD diagnosis. ON in NMOSD tended to have lower BCVA and lower inferior RNFL thickness than typical and atypical ON at initial presentation. There was no follow-up differences among the three groups in terms of BCVA and visual field improvement. The thinning of the RNFL and GCC at follow-up in the typical and atypical ON groups was more significant than that in the NMOSD group.

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