Yuichi Tagami

Axonal regeneration induced by repetitive electrical stimulation of crushed optic nerve in adult rats

PurposeTo investigate whether electrical stimulation promoted axonal regeneration of retinal ganglion cells (RGCs) after optic nerve (ON) crush in adult rats.MethodsTranscorneal electrical stimulation (TES), which stimulates the retina with current from a corneal contact lens electrode, was used to stimulate the eye. TES was applied for 1 h immediately after ON crush. Axonal regeneration was determined by anterograde labeling of RGC axons. To examine whether the axonal regeneration was mediated by insulin-like growth factor 1 (IGF-1) receptors, an IGF-1 receptor antagonist, JB3, was injected intraperitoneally before each TES application. Immunostaining for IGF-1 was performed to examine the effects of TES. To test the survival-promoting effects of TES applied daily, the mean density of retrogradely labeled RGCs was determined on day 12 after ON crush.ResultsCompared with sham stimulation, the mean number of regenerating axons significantly increased at 250 μm distal from the lesion and increased IGF-1 immunoreactivity was observed in retinas treated daily with TES. Preinjection of an IGF-1 receptor antagonist significantly blocked axonal regeneration by TES applied daily. TES applied daily also markedly enhanced the survival of RGCs 12 days after ON crush.ConclusionTES applied daily promotes both axonal regeneration and survival of RGCs after ON crush.

Transcorneal electrical stimulation improves visual function in eyes with branch retinal artery occlusion.

Purpose: To investigate the effects of transcorneal electrical stimulation (TES) on eyes that have a branch retinal artery occlusion (BRAO). Subjects and method: We studied two eyes having a BRAO, with an interval between the onset of symptoms and the beginning of treatment of >16 weeks (longstanding cases), and in three eyes with an interval of <16 weeks (fresh cases). The visual functions of the eyes were assessed by the best-corrected visual acuity (BCVA), multifocal electroretinograms (mfERGs), and automated static perimetry with the Humphrey field analyzer (HFA). The mfERGs were recorded before and 1 month after the TES, and perimetry with the HFA was done before and at 1 and 3 months after the TES. The amplitudes and implicit times of the N1, P1, and N2 components of the mfERGs were analyzed. Results: TES did not alter the BCVA significantly in all eyes, but it led to a significant increase in the amplitude of the N2 wave of the mfERGs (P < 0.01). The amplitude of the N1–P1 was also increased but not significantly. The implicit times of N1 (P < 0.01) and P1 (P < 0.05) were significantly shorter than that before the TES. The mean deviation of the HFA was increased after the TES but only in the longstanding cases. Conclusion: Our results indicate that TES improves the visual function in eyes with BRAO, mainly in longstanding cases.

Transcorneal electrical stimulation increases chorioretinal blood flow in normal human subjects.

Purpose The aim of this article is to investigate the effect of transcorneal electrical stimulation (TES) on chorioretinal blood flow in healthy human subjects. Methods The chorioretinal blood flow of 10 healthy subjects was measured before and after TES by laser speckle flowgraphy and expressed as the square blur rate (SBR). The chorioretinal blood flow was determined before and immediately after TES and 0.5, 1, 1.5, 2, 2.5, 3, 24, and 40 h after TES in three different areas: the margin of the optic disc, a point located midway between the optic disc and macula, and the macula area. The SBR of the stimulated eye is expressed relative to the value of the fellow eye. The mean standardized blur ratio was calculated as the ratio of the standardized SBR to the baseline SBR. The changes of intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were determined after each measurement of the SBR. The ocular perfusion pressure (OPP) was calculated from BP and IOP. Results The mean standardized blur ratio at the optic disc did not change significantly throughout the course of the experiment. However, the mean standardized blur ratio midway between the optic disc and macula and at the macula area were significantly higher after TES than that after sham stimulation at 3 and 24 h (P < 0.05, P < 0.01, respectively). At all times, the mean BP, PR, IOP, and OPP were not significantly different from the prestimulation values. Conclusions TES increases the chorioretinal blood flow in normal subjects with minimal effects on the systemic blood circulation and the IOP. The increase in chorioretinal blood flow may be one of the beneficial effects that TES has on ischemic retinal diseases.

Cilostazol promotes survival of axotomized retinal ganglion cells in adult rats

Cilostazol (CLZ), a selective inhibitor of cyclic nucleotide phosphodiesterase 3, has been shown to reduce neuronal cell death after a transient cerebral infarction. The mechanism for this reduction was suggested to be an elevation of intracellular cAMP or an inhibition of tumor necrosis factor alpha. Optic nerve injury leads to retinal ganglion cell (RGC) death possibly from a deprivation of neurotrophic factors and/or the down-regulation of intracellular cAMP. The purpose of this study was to determine if CLZ can rescue RGCs after optic nerve transection by inhibiting cyclic nucleotide phosphodiesterase 3. To examine this, the mean densities of surviving RGCs after optic nerve transection were determined in retinas that received an intravitreal injection of CLZ and in retinas that received vehicle. Our results showed that the density of surviving RGCs in the retina with intravitreal CLZ were significantly higher than that with vehicle injection on day 7. The CLZ was effective in promoting the survival at more than 0.05% concentration. The neuroprotective effects induced by 0.05% CLZ could be observed even 14 days after optic nerve transection. Furthermore, combined application of protein kinase A (PKA) inhibitor, KT5720 (10 microM) and 0.05% CLZ significantly decreased the density of surviving RGCs compared to that with only 0.05% CLZ. Based on these data, we concluded that CLZ enhances the survival of axotomized RGC in vivo, possibly depending on the activation of PKA pathway.

Pyroglutamic acid promotes survival of retinal ganglion cells after optic nerve injury.

Purpose: To determine whether pyroglutamic acid (PGA) enhances the survival of retinal ganglion cells (RGCs) after optic nerve (ON) transection in vivo and RGCs in culture. Methods: The RGCs of rats were retrogradely labeled by Fluorogold (FG)-soaked sponges placed on both superior colliculi. Seven days later, the ON was transected, and PGA was immediately injected into the vitreous. Seven or fourteen days later, the number of FG-labeled RGCs was counted on flat-mounted retinas to obtain the mean densities of FG-labeled RGCs. To determine whether the survival effect of PGA was related to excitatory amino acid transporter (EAAT), L-trans-pyrrolidine-2,4 dicarboxylate (PDC), a nonselective glutamate transport inhibitor, was injected into vitreous with the PGA. In primary retinal cultures, RGCs were identified as cells that were immunopositive to β III tubulin three days after beginning the culture with and without PDC. Results: The mean density of FG-labeled RGCs was reduced from 2249 ± 210 to 920 ± 202 cells/mm2 (p < 0.001) on day 7 after the ON transection. The mean density RGCs was significantly higher at 1213 ± 159 cells/mm2 after 0.5% PGA injection immediately after the ON transaction than eyes injected with the vehicle at 1007 ± 122 cells/mm2 (p = 0.035). One percent PGA was the most effective concentration for survival-promoting effects on RGCs, and the mean density of the RGCs was 1464 ± 102/mm2 (p < 0.001). Fourteen days after 1% PGA, the mean density of FG-labeled RGCs was significantly higher than that with vehicle (204 ± 23/mm2 versus 145 ± 17 cells/mm2; p < 0.01). Simultaneous application of 1% PGA and PDC blocked the survival effects of PGA on day 7 after ON transection. The presence of PGA increased the number of β III tubulin-positive cells. Conclusions: PGA promotes the survival of axotomized RGCs in adult mammalian retinas possibly mediated by the EAATs.

A study of static, kinetic, and dynamic visual acuity in 102 Japanese professional baseball players

Background It seemed that visual functions might have some effects on the performance of baseball players. We measured static, kinetic, and dynamic visual acuity (SVA, KVA, and DVA, respectively) of Japanese professional baseball players to ascertain whether there would be any difference in SVA, KVA, and DVA among player groups stratified according to their performance level. Methods The subjects were 102 male professional baseball players with a mean age of 26 years who were members of a Japanese professional baseball club from 2000 to 2009. They were stratified into three groups according to their performance level: A (players who were on the roster of the top-level team all the time throughout the study period), B (players who were on the roster of the top-level team sometimes but not all the time), and C (players who were never on the roster of the top-level team). They were interviewed for the use of corrective visual aids, and examined for SVA, KVA, and DVA. The measurements of these parameters were compared among groups A, B, and C. We also investigated and analyzed the association of KVA or DVA with player position (pitchers or fielders) and with hand dominance for batting. KVA was compared between the pitchers and the fielders because they each require different playing skills. DVA was compared between the right-handed and the left-handed batters. Results There was no statistically significant difference among groups A, B, and C. There was a statistically significant difference in KVA between the pitchers and the fielders (t-test; P < 0.05) There was no statistically significant difference in DVA between the right-handed and the left-handed batters. Conclusions There was no significant difference in the examined visual functions among player groups with different performance levels.

Erratum to: Axonal regeneration induced by repetitive electrical stimulation of crushed optic nerve in adult rats

The correct fi gure is shown on the right.

Acute bilateral peripheral cone system dysfunction.

PURPOSE To report electrophysiological and psychophysical findings in an unusual case with acute loss of the peripheral visual field bilaterally. METHODS A 19-year-old woman underwent fundus photography, fluorescein angiography, visual field testing, determination of full-field electroretinograms (ERGs) and multifocal ERGs (mfERGs), and rod-cone perimetry in addition to routine ophthalmologic examinations. RESULTS Findings of fundus examination and fluorescein angiography were completely normal, and best-corrected visual acuity was 1.0 in both eyes. However, static perimetry revealed a temporal field defect in the right eye and an arcuate scotoma in the left eye. Full-field ERG cone responses were significantly reduced, but rod responses were normal in both eyes. Psychophysical rod-cone perimetry demonstrated that the peripheral cone system was impaired whereas the rod sensitivity was completely normal. mfERGs showed that the local cone responses were well preserved in the central retina but were severely reduced in the peripheral retina in both eyes. CONCLUSIONS These results indicate that there is an unusual retinopathy showing acute dysfunction of the peripheral cone system bilaterally whereas the rod system is functioning normally.

Visual Hallucinations Following Stellate Ganglion Block in a Patient with Central Retinal Artery Occlusion

Successful treatment of foveal detachment and retinoschisis in an eye without a macular hole by vitrectomy and ILM peeling has been reported in patients with high myopia. In highly myopic eyes with a posterior staphyloma, the retinal pigment epithelium (RPE) and choroid are displaced posteriorly so that the retina must be stretched to contact the underlying structure. In this condition, the retina is under traction. Tangential traction of the retina by an epiretinal membrane (ERM) is also considered to be a cause of retinal detachment and retinoschisis in the posterior pole. Therefore, the complete removal of the ERM and/or overlying residual cortex by ILM peeling has been reported to repair the macular detachment successfully. Although our patient’s right eye was mildly myopic, there was a staphyloma in the inferior half of the fundus, and the RPE was atrophic in the macular area due to the tilted disc syndrome. These morphological abnormalities in the macular area, along with the intact posterior vitreous membrane, probably induced tangential traction on the retina and probably contributed to the development of the foveal detachment and retinoschisis without macular hole. At the initial visit, only the OCT examination disclosed the foveal retinal detachment and retinoschisis defi nitively. Thus, we recommend that OCT examinations be performed on patients with high myopia or tilted disc syndrome to search for macular changes when visual symptoms are present even when the fundus appears essentially normal.