Use of blue-on-yellow perimetry for detection of sectoranopia.
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Biomedical subjects
Publications and source records attributed to E Adachi-Usami.
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The long-chain polyunsaturated omega-3 fatty acid docosahexaenoic (22:6n-3) acid (DHA) accumulates in rod outer segment disks and synaptic terminals. It has been thought to play an important role in disordering disk membranes and in providing an adequate environment for conformational rhodopsin changes and in modifying the activity of retinal enzymes. The decrease of DHA content in the retina has been shown to affect visual function in monkey. In rat retina, prolonged light exposure has produced reduction of DHA content in rod outer segments. The authors found that when DHA was administered before ischemia, it diminished pressure-induced retinal damage. The recovery of electroretinographic amplitudes in DHA-pretreated eyes was significantly greater than those in the control eyes after 4 hr of reperfusion. The histopathologic study of control eyes showed cell swelling and cell nuclei pyknosis in the inner nuclear layer after 4 hr of reperfusion and in TUNEL-positive cells in the inner and outer nuclear layers after 24-72 hr of reperfusion. The DHA pre-treated eyes had fewer pyknotic nuclei and vacuolated spaces in the inner nuclear layer and no TUNEL-positive cells for up to 72 hr of reperfusion. The precise role of the polyunsaturated n-3 fatty acid has not been identified in the retina and other tissues. Our findings showed that DHA probably prevented sensory retina from ischemic-reperfusion cell damage not only by inhibiting the formation of hydroxyl radicals, but also by reducing the non-NMDA responses or the inflammatory responses.
PURPOSE: To determine new criteria for early detection of temporal hemianopia in patients with asymptomatic pituitary tumor. METHODS: Fifteen patients without visual symptoms had pituitary tumor and subtle defects or normal visual fields by Goldmann perimetry. Twelve patients with visual symptoms had pituitary adenoma and visual field defects detected by Goldmann perimetry. All were examined by automated perimetry. The relationship between the tumor and the optic chiasm was graded by magnetic resonance imaging (MRI) on a scale of 0-4. Grade number increased with extent of compression. Temporal hemianopia observed by automated perimetry was estimated from normal data (52 normal fields). Vertical step was determined from the number of adjacent pairs along the midline; sensitivity was lower in the temporal field than in the nasal field. Temporal depression was calculated by the quadrant sum of sensitivity. RESULTS: All patients with symptomatic pituitary adenoma had vertical step and temporal depression in the upper field. Nine of 15 patients without visual symptoms had vertical step or temporal depression. Of nine patients with temporal hemianopia, two of four patients had grade 1 compression, three of five had grade 2, and four of four had grade 3. CONCLUSIONS: New criteria by automated perimetry could detect temporal hemianopia in patients with asymptomatic pituitary tumor.
We investigate whether an artificial graft made by cultured Schwann cell, extracellular matrix (ECM) and trophic factors can provide the environment for the regeneration of retinal ganglion cell (RGC) axons in adult rats. Six kinds of artificial grafts were used: ECM (control); ECM and Schwann cells; ECM, Schwann cells and either nerve growth factor, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4); ECM, Schwann cells, BDNF and NT-4, combined with intravitreal injection of BDNF. The grafts were transplanted onto the transected optic nerve. RGC regeneration was evaluated by dil retrograde labeling, immunohistochemistry, and electron microscopy at 3 weeks post-operation. The degree of dil labeled RGC was approximately 2% for ECM alone, and 10% for ECM and Schwann cells (p < 0.01). The labeling increased to approximately 20% by administration of neurotrophins. The addition of intravitreous BDNF injection resulted in highest labeling percentage of 30%. Immunohistochemical study showed that axons were association with GAP-43 and cell adhesion molecules. Neurotrophin receptors (Trk-A and Trk-B) were detected in nerve fibers both in the retina and in the graft. Remyelination was seen by electron microscopic observation. These results demonstrate that the regeneration of RGC axons is induced with the use of cultured Schwann cells and ECM as promoting factors for regrowth. The degree of regeneration was significantly increased by neurotrophins in the grafts and in the vitreous.
PURPOSE: To investigate how central retinal function contributes to pattern visual evoked cortical potentials (PVECPs), we recorded transient and steady-state PVECPs in patients with macular disease and compared the results with those of patients with optic neuritis. The results were also evaluated for correlation with visual acuity and kinetic perimetric measurements. METHODS: PVECPs to 3 rev/s stimulation (transient) and 12 rev/s stimulation (steady-state) for check sizes 15' and 30' were obtained from all patients and age-matched healthy controls. The peak latency and amplitude of the P100 component of the transient VECP and the amplitudes of the steady-state VECP were measured and evaluated. RESULTS: Patients with macular disease produced significant delay of P100 latency and amplitude attenuation of the steady-state VECP, as compared with healthy subjects. P100 latency delay was less in patients with macular disease than in those with optic neuritis, while the attenuation rate of the steady-state VECP amplitude was similar between groups. Visual acuity was correlated with P100 latency and steady-state VECP amplitude reduction. CONCLUSIONS: Although the delay of latency was less in patients with macular disease than in those with optic neuritis, the electrophysiologic alterations that occur in macular disease demonstrate a potential for diagnostic value at the level of the retina.
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PURPOSE: To investigate the role played by docosahexaenoic acid (DHA) in the retina, and more specifically, its ability to protect the retina from kainic acid (KA)-induced retinal damage. METHODS: Three-week-old female Wistar rats were used. DHA (1000 mg/kg per day) was fed to the rats for 7, 14, and 28 days, and the concentrations of DHA and arachidonic acid (AA) in the retina and serum were measured. In another group of rats, the right eyes were injected intravitreally with 3.12 nanomoles KA after DHA supplementation for 14 days. Electroretinograms (ERGs) elicited by different stimulus intensities were recorded before and on days 1, 7, and 14 after the KA injection. The amplitudes and implicit times of the a- and b-waves were compared. The number of cells in the ganglion cell layer (GCL) and inner nuclear layer (INL) were compared by histopathologic examination. RESULTS: The concentration of DHA in the serum and retina increased after DHA supplementation. The concentration of AA in serum decreased with DHA supplementation, but the concentration of AA in retina did not show any significant change. The b-waves of the ERGs recorded after KA injection were significantly attenuated in both groups of rats. However, the attenuation was significantly less in the DHA-supplemented rats than in gum arabic-supplemented control rats. The numbers of cells in the INL and GCL were significantly higher in DHA-supplemented rats. CONCLUSIONS: These results indicate that DHA supplementation can partially counteract KA neurotoxicity in the rat retina. DHA may play a role in modulating neuronal excitability by reducing KA-induced responses in the retina.
PURPOSE: To examine the effect of myopia, occasionally associated with glaucomatous eyes, on the results obtained by frequency-doubling perimetry (FDP). METHODS: Sixty emmetropic or myopic normal volunteers (mean age, 26.2 +/- 0.35 years, mean +/- SEM; range, 19-34) with good visual acuity and without glaucoma were divided into three groups. The groups were emmetropia to low-myopia (mean refractive error, -1.16 +/- 0.23 D), intermediate-myopia (-4.95 +/- 0.17 D), and high-myopia (-8.12 +/- 0.36 D; n = 20 each). All subjects were tested on the FDP full-threshold C-20 program and the Humphrey Field Analyzer (HFA; Humphrey, Dublin, CA) full-threshold program on one randomly selected eye. FDP and the HFA test were conducted with the subjects wearing their full distance correction and with their distance correction with appropriate additional correction for near, respectively. The calculated mean sensitivity (MS), mean deviation (MD), pattern standard deviation (PSD), and test durations for FDP and the HFA test for the three groups were compared using one-way analysis of variance. The relationship between the refractive error and MS, MD, or PSD was also analyzed by simple regression analysis. RESULTS: The MS and MD for the fields determined by the HFA decreased significantly as the refractive errors increased, but there were no significant differences in the MS, MD, and PSD for FDP between the three groups. There were no significant differences in the test durations between the three groups for both FDP and HFA testing. The refractive error was correlated with both MS and MD only for the fields determined by the HFA. CONCLUSIONS: The results showed that lens-corrected myopia does not alter the visual fields obtained by FDP, and FDP can therefore be used regardless of the presence of myopia.
PURPOSE: To determine whether the Hsp27 protein can rescue retinal ganglion cells (RGCs) of rats from ischemia-reperfusion injury. METHODS: Retinal ischemia was induced in rats by clamping the ophthalmic artery within the dural sheath of the optic nerve. Immediately after removing the clamp and beginning the reperfusion, Hsp27 protein solution was injected into the vitreous, and electroporation was applied. To determine whether Hsp27 entered the RGCs, anti-Hsp27 immunohistochemistry was performed. The retinal damage was evaluated by counting the number of RGCs retrogradely labeled by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine percholorate (diI) injected into the superior colliculus, and also by comparing the ratio of TUNEL-positive to all RGCs in the RGC layer. RESULTS: Electroporation successfully delivered Hsp27 protein into RGCs. In the Hsp27 electroinjected group, the number of RGCs 7 days after ischemia-reperfusion was significantly higher than in the control groups. The ratio of TUNEL-positive cells to all RGCs was lower in the group electroinjected with Hsp27 protein. CONCLUSIONS: Electroporation of Hsp27 protein into RGCs increased the resistance of the RGCs to the apoptosis induced by ischemia-reperfusion injury.
It is a well known fact that the injured PNS can successfully regenerate, on the other hand, the CNS such as retinal ganglion cell (RGC) axons of adult mammals is incapable of regeneration. After injury, RGC axons rapidly degenerate and most cell bodies go through the process of cell death, while glial cells at the site of injury undergo a series of responses which underlie the so-called glial scar formation. However, it has become apparent that RGCs do have an intrinsic capacity to regenerate which can be elicited by experimental replacement of the inhibitory glial environment with a permissive peripheral nerve milieu. Schwann cells are a major component of the PNS and play a role in regeneration, by producing various kinds of functional substances such as diffusible neurotrophic factors, extracellular matrix and cell adhesion molecules. RGC regeneration can be induced by cooperation of these substances. The contact of RGC axons to Schwann cells based upon the structural and molecular linkages seems to be indispensable for the stable and successful regeneration. In addition to cell adhesion molecules such as NCAM and L1, data from our laboratory show that Schwann cells utilize short focal tight junctions to provide morphological stabilization of the contact with the elongating axon, as well as a small scale of gap junctions to facilitate traffic of substances between them. Moreover, our results show that modifications of functional properties in neighboring glial cells of optic nerve are induced by transplantation of Schwann cells. Astrocytes usually considered to form a glial scar guide the regenerating axons in cooperation with Schwann cells. A decrease of the oligodendrocyte marker O4 and migration of ED-1 positive macrophages is observed within the optic nerve stump. Accordingly, RGC regeneration is not a simple phenomenon of axonal elongation on the Schwann cell membrane, but is based on direct and dynamic communication between the axon and the Schwann cell, and is also accompanied by changes and responses among the glial cell populations, which may be partly associated with the mechanisms of optic nerve regeneration.
PURPOSE: To evaluate whether and how VECPs are useful in differentiating ION from ON. METHODS: We retrospectively studied 27 patients with non-arteritic ION and 69 patients with ON using pattern visually evoked cortical potentials (PVECPs) to 3 rev/sec stimulation (transient) and 12 rev/sec stimulation (steady-state). RESULTS: In patients with ION, non-recordable responses were found in 25% of those with transient VECP and in 74% of those with steady-state VECP. In ON patients, non-recordable responses were found in 34% of those with transient VECP and in 64% of those with steady-state VECP. The average peak latency of P100 component in those with ION was significantly shorter than in those with ON. The amplitude ratio (affected eye/fellow eye) of steady-state VECP was significantly higher in those with ION than in those with ON. The amplitude ratio of P100 showed no significant differences between groups. CONCLUSION: The P100 peak latency of transient VECPs and the amplitude of steady-state VECPs have the potential to differentiate between ION and ON.
PURPOSE: To study the visual field with frequency doubling technology (FDT) in patients with recovered optic neuritis and to detect loss of magnocellular projecting cells (M cells) in the extrafovea. METHODS: Fourteen patients who had undergone one attack of optic neuritis and recovered normal vision (1.0 or better) and critical fusion frequency were examined with conventional Humphrey automated perimetry central 30-2 and FDT c-20 threshold tests. After 1 year, 12 patients were reexamined with central 30-2 and FDT c-20 tests. The visual fields examined by both perimeters were divided into three zones. The mean sensitivity in each zone in involved eyes, uninvolved eyes, and involved eyes after 1 year was compared with that in healthy eyes. RESULTS: Conventional automated perimetry showed depression toward the fovea. However, FDT demonstrated general depression, especially midperipheral deficits. After 1 year, the midperipheral deficits with frequency doubling perimetry (FDP) improved, as did central depression, as observed with central 30-2 tests. CONCLUSIONS: FDT was developed to detect early glaucomatous damage, which was thought to be caused by a loss of M cells. Our study suggested that patients with resolved optic neuritis also had a loss of M-cell function in the extrafoveal area, as observed by field damage and its recovery.
Optic neuritis is a clinical syndrome resulting from inflammation, demyelination, or infection of the optic nerve. Its diagnosis and treatment are complicated. In 1884, Nettleship first reported 28 cases of optic neuritis whose clinical symptoms have been accepted up to the present without any change. On the other hand, the development of diagnostic procedures and steroid therapy have also altered the clinical features of optic neuritis. Among several developed diagnostic procedures, the visually evoked cortical potential (VECP) has become a good tool to prove the impairment of the optic nerve. In 1971, we reported a decrease of threshold intensity required to evoke VECPs in optic neuritis patients whose visual acuity was relatively well preserved. In the same year, Halliday et al. reported that pattern VECP (PVECP) was delayed in 93% of patients with multiple sclerosis (MS) without optic neuritis. Stimulated by this report, a great number of studies appeared to show the usefulness of PVECP in the diagnosis of MS. However, few of these studies gave descriptions of ophthalmic findings. PVECP later become known to be closely related with ophthalmic conditions. In the ophthalmological field, we reported the influence of pupillary size, accommodation power, refractive powers, eccentricity of stimulated retinal area, retinal luminance, contrast, wavelengths, spatial and temporal frequencies, stimulus field etc. On the basis of our results, we developed a television display system in 1975 and applied it clinically. In the present study, we reviewed the medical records of a total of 272 cases of optic neuritis who presented in our clinic between 1978 and 1999. In the diagnostic, therapeutic point of view in relation with the data of other countries, the study was important regarding the racial differences and recent conceptions of optic neuritis. The results showed that there were no racial difference in optic neuritis as had been thought. The development from optic neuritis to multiple sclerosis was not less than in Caucasian patients. Regarding steroid therapy, we found that the most effective method was sub-Tenon injection. For cases which recur and progress to optic atrophy, optic nerve transplantation will be needed. Therefore, we have been studying the reconstruction of the optic nerve in Wister rats. We experimentally damaged the ganglion cells by causing ischemic retina with ligation of the ophthalmic artery and cutting the optic nerve just behind the eyeball. To prevent the apoptosis of ganglion cells, we injected various neurotrophic factors such as BDNF, GDNF, and HSP 27 into the vitreous. For effective injection of DNA, electropolation was applied and the best condition for avoiding apoptosis was chosen. Further, in Mx-c-fos transgenic mice, we found that regeneration of ganglion cells was inhibited. Based on the rescue study of the ganglion cells, optic nerve transplantation was performed using an artificial graft in which cultured Schwann cells from the ischiatic nerve, BDNF, CNTF, insulin, and forscolin were compound and bridged to the superior colliculus. The results showed a regeneration rate of the optic nerve axon of 15%. This rate was much higher than in other reports. Keratoplasty and intraocular lens implantation had a relatively long history of research before achieving clinical success. We believe that optic nerve transplantation will one day be successful in clinical treatment in the same way.
The authors report a patient with an axonal Guillain-Barré syndrome (acute motor axonal neuropathy) associated with anti-GM1 antibody after Haemophilus influenzae infection. The result of ELISA inhibition studies and cytochemical staining with cholera toxin suggest the presence of a GM1-like structure on the surface of H. influenzae isolated from the patient. A particular strain of H. influenzae may have a GM1-like structure and may elicit an axonal Guillain-Barré syndrome.
34 patients with indirect traumatic optic neuropathy were studied to identify factors affecting outcome and surgical indications. 12 cases (13 eyes = group A) underwent surgery and 24 patients (24 eyes = group B) were managed without surgery. Age, optic canal fracture, visual acuity before treatment (initial visual acuity) and days until surgery (only group A) were employed as variables. Visual acuity improved significantly more in patients with initial visual acuity, hand movement (HM) or better than in those with initial visual acuity for light perception (LP) only or worse. When initial visual acuity was HM or better, vision improved significantly more in patients with surgery than in those without surgery (p = 0.0003 by Mann-Whitney U test). Days until surgery were correlated with visual improvement in patients with visual acuity HM or better. Age and optic canal fracture did not affect visual improvement or influence the decision for or against surgery.
Gorlin syndrome (GS) is an autosomal dominant disorder in which patients are abnormally susceptible to ionizing radiation with radiotherapeutic doses. Radiogenic basal cell carcinomas may develop with a short latent period in patients. The mechanisms underlying the abnormal radiosusceptibility of cells in patients with GS has not been well characterized. In this study we report an increase in the number of nucleoli in fibroblast cells from 3 patients with GS after x-radiation. In GS fibroblasts, the increase in nucleolus number concomitant with the increase of ribonucleoprotein immunoreactive aggregates within the nucleus was observed after x-radiation, whereas significant change was not found in normal fibroblasts derived from healthy donors. This increase disappeared when cells were cultured with the RNA synthesis inhibitor actinomycin D after x-radiation but not when they were cultured with cycloheximide or aphydicolin, which are protein and DNA synthesis inhibitors, respectively. Ultraviolet exposure did not induce remarkable changes in the GS nucleoli. Thus the increase in nucleoli was induced after x-radiation of GS fibroblasts, and this increase seemed to be related to RNA synthesis metabolism.