[New insights into the study of optic nerve diseases]

Optical coherence tomography (OCT) provides a new dimenstion in ophthalmology because it allows evaluation of the pathology in vivo, and provides information to assist the management of macular disease and glaucoma. It is necessary to differentiate the diagnosis of glaucoma from diseases of the optic nerve and of the visual pathway. This study evaluates the usefulness of OCT in detecting disorders of the optic nerve and visual pathway. In addition, the pathogenesis of glaucomatous optic neuropathy (GON), the most common optic neuropathy, was investigated by focusing on the dynamics of aquaporin. I. Evaluation of optic nerve and visual pathway disorders by optical coherence tomography. The swinging flashlight test is an easy, sensitive, objective test to detect relative afferent pupillary defects (RAPD). The number of RAPD detected by the swinging flashlight test was closely correlated with the ratio of retinal nerve fiber layer thickness (RNFLT) between the two eyes of 20 cases of unilateral optic atrophy. OCT could assess the amount of RAPD that reflected an asymmetrical functional disturbance of the optic nerves, as a structural difference. The time courses of RNFLT and ganglion cell complex (GCC) changes' were observed immediately following the time of injury in 4 cases of traumatic optic neuropathy. OCT revealed that both the RNFLT and GCC decreased rapidly from 2 weeks after the injury until 20 weeks later. The RNFLT decreased significantly in the horizontal direction in comparison to the perpendicular direction in 34 eyes from the cases of optic chiasm syndrome. This means that OCT could quantitatively detect the band atrophy of the optic disc in optic chiasm syndrome. Measuring the RNFLT showed a thinning of RNFLT in the perpendicular direction in comparison to the horizontal direction in ipsilateral eyes and thinning in the horizontal direction in comparison to the perpendicular direction in the contralateral eyes in optic tract syndrome. Measuring the GCC showed a thinning of the GCC in the temporal hemifield to the central fovea of the ipsilateral eyes, and thinning of the GCC in the nasal hemifield of the contralateral eyes. This means that OCT could detect the structural changes of hourglass atrophy in the ipsilateral eye and band atrophy in the contralateral eye at the optic disc as well as the homonymous hemianopia in the visual field. OCT was useful in evaluating the optic nerve and visual pathway disorders, but there were also some limitations. The thinning area of RNFLT measured by OPTVue and Cirrus were in entirely opposite directions in cases of optic chasm syndrome. The reason was attributed to the better performance of RTVue in measuring a thin RNFLT on the nasal side of the optic disc in comparison to Cirrus. The specific characteristics of the instruments should be considered when the results of OCT are evaluated. II. Dynamics of aquaporin in the optic nerve Aquaporin (AQP) is a membrane protein that forms a water channel to facilitate water crossing the plasma membrane. AQP-4 was originally thought to be expressed in the optic nerve, but it is expressed only in the retrobulbar medullated region of the optic nerve and the expression of AQPs in the optic disc has not been detected. This study investigated the expressions of AQPs in the optic nerve in rat, monkey and human. The results demonstrate that only AQP-9 was expressed at the unmedullated pre-lamina cribrosa and lamina cribrosa regions, and both AQP-4 and AQP-9 were expressed at the medullated retrobulbar region. Astrocytes were observed to express AQP-9, because AQP-9 immunoreactivity was identical to that of glial fibrillary acidic protein. Elevated intraocular pressure substantially reduced AQP-9 expression in the optic nerve, whereas expression of AQP-4 was not changed in rat eyes. The same phenomena were also observed in the monkey eye with ocular hypertension as well as human eye with glaucoma. AQP-9 is an aquaglyceroporin that allows solutes such as lactate rather than water to cross the cell membrane. The astrocyte-to-neuron lactate shuttle hypothesis has been proposed, in which lactate transported from astrocytes is used by neurons as an energy substrate. Reduction of AQP-9 expression in the optic nerve head under elevated intraocular pressures might be closely related to the pathogenesis of GON.