Comparison of visual fatigue caused by head-mounted display for virtual reality and two-dimensional display using objective and subjective evaluation.

This study aimed to evaluate objective and subjective visual fatigue experienced before and after performing a visual task while using a head-mounted display for virtual reality (VR-HMD) and two-dimensional (2D) display. Binocular fusion maintenance (BFM) was measured using a binocular open-view Shack-Hartmann wavefront aberrometer equipped with liquid crystal shutters. Twelve healthy subjects performed the BFM test and completed a questionnaire regarding subjective symptoms before and after performing a visual task that induces low visually induced motion sickness (VIMS). BFM (p = .87) and total subjective eye symptom scores (p = .38) were not significantly different between both groups, although these values were significantly lower after the visual task than before the task within both groups (p < .05). These findings suggest that visual fatigue after using a VR-HMD is not significantly different from that after using a 2D display in the presence of low-VIMS VR content. Practitioner summary: Objective and subjective evaluation of visual fatigue were not significantly different with the use of a head-mounted display for virtual reality (VR-HMD) and two-dimensional display. These results should be valuable not only to engineers developing VR content but also to researchers involved in the evaluation of visual fatigue using VR-HMD. Abbreviations: VR: virtual reality; VR-HMD: head-mounted display for virtual reality; BFM: binocular fusion maintenance; BWFA: binocular open-view Shack-Hartmann wavefront aberrometer.

Expression levels of ABCG2 on cord red blood cells and study of fetal anemia associated with anti-Jr(a).

BACKGROUND: The Jr(a) antigen of JR blood group systems is located on ABCG2 and Jr(a-) subjects whose red blood cells (RBCs) lack ABCG2 have been identified mostly among the Japanese. Although anti-Jr(a) can cause fetal anemia, little is known regarding its mechanism. STUDY DESIGN AND METHODS: We reviewed clinical courses of all reported cases with fetal anemia due to anti-Jr(a) . We analyzed the ABCG2 expressions of cord RBCs at various gestational ages. We examined the effects of sera containing anti-Jr(a) from three pregnancies with fetal anemia or monoclonal anti-Jr(a) on erythropoiesis and phagocytosis. We also examined epitopes of anti-Jr(a) . RESULTS: Case series suggested that the majority of fetal anemia with anti-Jr(a) may not be progressive in the later gestational ages. ABCG2 expression levels of cord RBCs were significantly higher than those of adults and neonates with high individual variation and gradually decreased with advancing gestational ages. Anti-Jr(a) did not significantly impact erythroid colony formation, although we detected a tendency toward the suppression of erythroid burst-forming unit formation by anti-Jr(a) using feline marrow cells. Anti-Jr(a) did not induce phagocytosis of sensitized RBCs by monocytes. While many anti-Jr(a) recognized the same regions as a monoclonal anti-ABCG2, 5D3, epitopes of anti-Jr(a) did not correlate with the incidence of fetal anemia. CONCLUSION: ABCG2 expression levels in cord RBCs are higher than those of adults, and the change of ABCG2 expression in erythroid lineage cells may influence the clinical course of fetal anemia with anti-Jr(a) , although we could not detect significant effects of anti-Jr(a) on erythroid colony formation or phagocytosis.

Surgical feasibility and biocompatibility of wide-field dual-array suprachoroidal-transretinal stimulation prosthesis in middle-sized animals.

PURPOSE: To investigate the safety and efficacy of a newly-developed wide-field dual-array suprachoroidal-transretinal stimulation (STS) prosthesis in middle-sized animals. METHODS: The prosthesis consisted of two arrays with 50 to 74 electrodes. To test the feasibility of implanting the prosthesis and its efficacy, the prosthesis was implanted for 14 days into two rabbits. Optical coherence tomography (OCT) and ophthalmoscopy were performed 7 and 14 days after the implantation. Then the rabbits were euthanized, eyes were enucleated, and the posterior segment of the eye was examined histologically. In a second experiment, the arrays were implanted into two cats, and their ability to elicit neural responses was determined by electrically evoked potentials (EEPs) at the chiasm and by optical imaging of the retina. RESULTS: All arrays were successfully implanted, and no major complications occurred during the surgery or during the 2-week postoperative period. Neither OCT nor ophthalmoscopy showed any major complications or instability of the arrays. Histological evaluations showed only mild cellular infiltration and overall good retinal preservation. Stimulation of the retina by the arrays evoked EEPs recorded from the chiasm. Retinal imaging showed that the electrical pulses from the arrays altered the retinal images indicating an activation of retinal neurons. The thresholds were as low as 100 µA for a chiasm response and 300 µA for the retinal imaging. CONCLUSION: Implantation of a newly-developed dual-array STS prosthesis for 2 weeks in rabbits was feasible surgically, and safe. The results of retinal imaging showed that the dual-array system was able to activate retinal neurons. We conclude that the dual-array design can be implanted without complication and is able to activate retinal neurons and optic nerve axons.

The influence of stimulating electrode conditions on electrically evoked potentials and resistance in suprachoroidal transretinal stimulation.

PURPOSE: To determine the influence of stimulating electrode conditions on the amplitudes and latencies of electrically evoked potentials (EEPs) and the resistance at the electrode-tissue interface in the suprachoroidal transretinal stimulation (STS) system. STUDY DESIGN: Experimental study. METHODS: A scleral pocket (3 × 5 mm) was created just over the visual streak in anesthetized pigmented rabbits (weight, 1.9-2.7 kg), and STS stimulating electrodes were implanted into the pocket. Measurements were obtained with stimulating electrodes of different lengths (0.3 or 0.5 mm) and different surface characteristics (smooth or porous). EEPs elicited with a fixed current under each set of electrode conditions were recorded; three measurement sessions were performed for each rabbit. The resistance at each electrode-tissue interface was measured. RESULTS: The latencies and amplitudes of the EEPs did not differ significantly with changes in the height and surface characteristics of the stimulating electrodes, but the resistances at the electrode-tissue interface differed significantly (P = 0.001; the resistance values for the 0.3-mm-long electrode with a porous surface was 5.24 ± 0.67 kΩ and with the 0.3- and 0.5-mm-long electrodes with smooth surfaces were 7.63 ± 0.12 kΩ and 6.77 ± 0.20 kΩ). CONCLUSION: Being shorter did not affect the EEPs of the stimulating electrodes with a porous surface while decreasing the resistance at the electrode-tissue interface.

Spatial Resolution of Suprachoroidal-Transretinal Stimulation Estimated by Recording Single-Unit Activity From the Cat Lateral Geniculate Nucleus.

Retinal prostheses are devices used to restore visual sensation in patients suffering from photoreceptor degeneration, such as retinitis pigmentosa. Suprachoroidal-transretinal stimulation (STS) is a prosthesis with retinal electrodes located in the sclera. STS has the advantage that it is safer than epiretinal or subretinal prostheses, as the implant is not directly attached to the retinal tissue. We have previously reported feasibility of STS with animal experiments and clinical trials. However, functional evaluation with neurophysiological experiments is still largely missing. To estimate the spatial resolution of STS, single-unit activities in response to STS were recorded from relay cells in the dorsal lateral geniculate nucleus of cats, and the response probability of the units was analyzed in relation to the distance between the stimulus location and the receptive field of each recorded unit. A platinum electrode was attached to the sclera after lamellar resection, and the return electrode was placed in the vitreous. The stimulating current, which ranged from 50 to 500 µA, was applied between these electrodes, and the probability of spike responses occurring just after retinal stimulation was measured. The distance at half-maximum of response was determined from the collected response probabilities as a function of stimulus intensity for all units characterized by their distances from the receptive field center to the stimulation point. As the stimulation became weaker, this distance decreased to 1.8° at 150 and 100 µA. As another estimation, the radius of 25% response probability was 1.4° at 100 µA. The diameter of the stimulated cat retinal area, 3.6° or 2.8°, corresponds to human visual acuity of 0.005 or 0.007, or finger counting. Considering the lower hazard to the retina of STS and its potentially large visual field coverage, STS is an attractive method for retinal prosthetic device development.

Testing of Newly Developed Wide-Field Dual-Array Suprachoroidal-Transretinal Stimulation Prosthesis in Dogs.

Purpose: This study was conducted to investigate the feasibility of a newly developed wide-field dual-array suprachoroidal-transretinal stimulation (STS) prosthesis in dogs and to examine its biocompatibility and stability over a 4-month period. Methods: Three types of STS dual arrays were designed and tested. The STS dual-array was implanted into a scleral pocket of the left eye of six healthy beagle dogs. Ophthalmic examinations, fundus photography, fluorescein angiography (FA), electroretinography (ERG), and functional testing of this system were conducted postoperatively. The dogs were euthanatized at the end of the experiment, and their eyes were enucleated and histologically examined. Results: All prostheses were successfully implanted without complications, and no serious adverse event occurred during the postoperative period. Fundus photographs and FA showed no serious damage in the retina surrounding the arrays. The ERGs recorded from the implanted eyes showed no significant differences from those from control eyes. Histological evaluations demonstrated good preservation of the retina over the array. However, system failure occurred in 50% of the dogs owing to dog-specific habits. Conclusions: Implantation of this prosthesis system in dogs is feasible and can be performed without significant damage to the eye. The biocompatibility and stability of the array were good during the observation period, but the low durability of the system against dogs (not humans) is an issue to be resolved in the future. Translational Relevance: This study suggests that this wide-field dual-array prosthesis might widen the visual field and might be useful for patients with retinitis pigmentosa.

Optimal parameters of transcorneal electrical stimulation (TES) to be neuroprotective of axotomized RGCs in adult rats.

We previously showed that transcorneal electrical stimulation (TES) promoted the survival of axotomized retinal ganglion cells (RGCs) of rats. However the relationship between the parameters of TES and the neuroprotective effect of TES on axotomized RGCs was unclear. In the present study, we determined whether the neuroprotective effect of TES is affected by the parameters of TES. Adult male Wistar rats received TES just after transection of the left optic nerve (ON). The pulse duration, current intensity, frequency, waveform, and numbers of sessions of the TES were changed systematically. The alterations of the retina were examined histologically seven days or fourteen days after the ON transection. The optimal neuroprotective parameters were pulse duration of 1 and 2 ms/phase (P < 0.001, each), current intensity of 100 and 200 muA (P < 0.05, each), and stimulation frequency of 1, 5, and 20 Hz (P < 0.001, respectively). More than 30 min of TES was necessary to have a neuroprotective effect (P < 0.001). Symmetric pulses without an inter-pulse interval were most effective (P < 0.001). Repeated TES was more neuroprotective than a single TES at 14 days after ON transection (P < 0.001). Our results indicate that there is a range of optimal neuroprotective parameters of TES for axotomized RGCs of rats. These values will provide a guideline for the use of TES in patients with different retinal and optic nerve diseases.

Simultaneous Measurement of Objective and Subjective Accommodation in Response to Step Stimulation.

Purpose: This study aimed to evaluate differences in objective and subjective accommodation dynamically and simultaneously. Methods: Thirty-four pre-presbyopic healthy volunteers (mean age ± SD, 41.0 ± 3.2 years) participated in this study. Initially, the reaction time for detecting a change in the target was measured at near. Dynamic accommodation was then monocularly recorded using an open-view Shack-Hartmann aberrometer and compared with the amplitude and velocity of subjective accommodation. Results: The objective amplitude of accommodation (0.97 ± 0.32 diopter [D]) was significantly greater than the subjective amplitude of accommodation (0.62 ± 0.43 D; P < 0.001). The accommodative velocity was significantly faster for the "before the accommodation" response time (0.47 ± 0.38 D/s) than the "after the accommodation" response time (0.21 ± 0.22 D/s; P = 0.007). Conclusions: The human eye under the monocular condition quickly adjusts to the focal plane to clearly archive the nearby object, and the focal plane thereafter is slowly and accurately adjusted to the visual target after visual recognition.

Binocular Coordination during Smartphone Reading in Esophoric Patients.

Purpose: To evaluate binocular coordination using video-oculography (VOG) during smartphone reading in patients with esophoria (EP) compared with control subjects.Patients and methods: Ten young and adult patients with EP (25.3 ± 7.3 years) and seven orthophoric or small-angle exophoric control subjects (25.7 ± 4.8 years) were examined. Eye movements were recorded during smartphone reading at 20, 30, and 50 cm using VOG. Differences in the horizontal fixation disparity at each distance between and within the groups were analyzed.Results: Horizontal esodeviation at 20 cm in the EP group (1.23° ± 2.00°) was significantly greater than that at 30 cm (-0.39° ± 0.73°; P = .027) and was significantly greater than horizontal exodeviation at 20 cm in the control group (-0.21° ± 0.17°; P < .001).Conclusion: The current findings suggest that the horizontal fixation disparities in the patients with EP deviate to eso-direction during smartphone use.

Objective evaluation of visual fatigue in patients with intermittent exotropia.

PURPOSE: The purpose of this study was to evaluate the degree of visual fatigue in patients with intermittent exotropia (IXT) using the binocular fusion maintenance (BFM) test. METHODS: Fourteen patients with IXT (32.1 ± 16.4 years) and 15 age-matched healthy volunteers (31.2 ± 9.3 years) participated in the study. BFM was assessed by measuring the transmittance of liquid crystals placed in front of the subject's nondominant eye at the instance when binocular fusion was broken and vergence eye movement was induced. A questionnaire on subjective symptoms was administered to the subjects before and after the visual task. The visual task consisted of a reciprocal movement between 67 and 40 cm. RESULTS: The change [post-pre] of BFM was significantly lower in the IXT group (-0.185 ± 0.187) than in the control group (-0.030 ± 0.070) (P = 0.010). The change of total subjective eye symptom score was significantly greater in the IXT group (2.28 ± 1.43) than in the control group (0.93 ± 1.27) (P = 0.018). The reduction in BFM rate with increasing total subjective eye symptom score was significantly greater in the IXT group (-0.106 ± 0.017) than in the control group (-0.030 ± 0.013) (P = 0.006). CONCLUSION: The present findings objectively showed that patients with IXT are at a greater risk of visual fatigue in comparison with healthy individuals.

Learning process for identifying different types of communication via repetitive stimulation: feasibility study in a cultured neuronal network.

It is well known that various types of information can be learned and memorized via repetitive training. In brain information science, it is very important to determine how neuronal networks comprising neurons with fluctuating characteristics reliably learn and memorize information. The aim of this study is to investigate the learning process in cultured neuronal networks and to address the question described above. Previously, we reported that the spikes resulting from stimulation at a specific neuron propagate as a cluster of excitation waves called spike wave propagation in cultured neuronal networks. We also reported that these waves have an individual spatiotemporal pattern that varies according to the type of neuron that is stimulated. Therefore, different spike wave propagations can be identified via pattern analysis of spike trains at particular neurons. Here, we assessed repetitive stimulation using intervals of 0.5 and 1.5 ms. Subsequently, we analyzed the relationship between the repetition of the stimulation and the identification of the different spike wave propagations. We showed that the various spike wave propagations were identified more precisely after stimulation was repeated several times using an interval of 1.5 ms. These results suggest the existence of a learning process in neuronal networks that occurs via repetitive training using a suitable interval.

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.

Binocular coordination and reading performance during smartphone reading in intermittent exotropia.

PURPOSE: This study aimed to evaluate binocular coordination using video-oculography during smartphone reading in patients with intermittent exotropia compared to individuals with normal vision. PATIENTS AND METHODS: Eleven youth and adult patients with intermittent exotropia (21.9±9.3 years) and 15 control subjects (26.6±4.3 years) were examined. Eye movements were recorded during smartphone reading at 50, 30, and 20 cm using video-oculography. The loss of binocular coordination was tentatively defined as a horizontal disparity greater than 2°. The proportion of monocular viewing was the percentage of time for which binocularity was lost during smartphone reading. The proportion of monocular viewing, the reading speed, and the correlation between proportion of monocular viewing and reading speed were analyzed. RESULTS: The proportion of monocular viewing during smartphone reading was significantly higher in the intermittent exotropia group than in the control group (P<0.001). It was significantly more frequent at 20 cm than at 50 cm in the intermittent exotropia group (P<0.05). The reading speed was significantly negatively correlated with the proportion of monocular viewing at 30 and 20 cm in the intermittent exotropia group (P<0.05). CONCLUSION: A significant increase in the proportion of monocular viewing in the intermittent exotropia group suggests that an appropriate viewing distance should be advised so that users can maintain binocular coordination when viewing a smartphone.

Effect of correlating adjacent neurons for identifying communications: Feasibility experiment in a cultured neuronal network.

Neuronal networks have fluctuating characteristics, unlike the stable characteristics seen in computers. The underlying mechanisms that drive reliable communication among neuronal networks and their ability to perform intelligible tasks remain unknown. Recently, in an attempt to resolve this issue, we showed that stimulated neurons communicate via spikes that propagate temporally, in the form of spike trains. We named this phenomenon "spike wave propagation". In these previous studies, using neural networks cultured from rat hippocampal neurons, we found that multiple neurons, e.g., 3 neurons, correlate to identify various spike wave propagations in a cultured neuronal network. Specifically, the number of classifiable neurons in the neuronal network increased through correlation of spike trains between current and adjacent neurons. Although we previously obtained similar findings through stimulation, here we report these observations on a physiological level. Considering that individual spike wave propagation corresponds to individual communication, a correlation between some adjacent neurons to improve the quality of communication classification in a neuronal network, similar to a diversity antenna, which is used to improve the quality of communication in artificial data communication systems, is suggested.

Objective Evaluation of Visual Fatigue Using Binocular Fusion Maintenance.

PURPOSE: In this study, we investigated whether an individual's visual fatigue can be evaluated objectively and quantitatively from their ability to maintain binocular fusion. METHODS: Binocular fusion maintenance (BFM) was measured using a custom-made binocular open-view Shack-Hartmann wavefront aberrometer equipped with liquid crystal shutters, wherein eye movements and wavefront aberrations were measured simultaneously. Transmittance in the liquid crystal shutter in front of the subject's nondominant eye was reduced linearly, and BFM was determined from the transmittance at the point when binocular fusion was broken and vergence eye movement was induced. In total, 40 healthy subjects underwent the BFM test and completed a questionnaire regarding subjective symptoms before and after a visual task lasting 30 minutes. RESULTS: BFM was significantly reduced after the visual task (P < 0.001) and was negatively correlated with the total subjective eye symptom score (adjusted R2 = 0.752, P < 0.001). Furthermore, the diagnostic accuracy for visual fatigue was significantly higher in BFM than in the conventional test results (aggregated fusional vergence range, near point of convergence, and the high-frequency component of accommodative microfluctuations; P = 0.007). CONCLUSIONS: These results suggest that BFM can be used as an indicator for evaluating visual fatigue. TRANSLATIONAL RELEVANCE: BFM can be used to evaluate the visual fatigue caused by the new visual devices, such as head-mount display, objectively.

Transcorneal electrical stimulation promotes the survival of photoreceptors and preserves retinal function in royal college of surgeons rats.

PURPOSE: To determine whether transcorneal electrical stimulation (TES) has neuroprotective effects on photoreceptors and preserves retinal function in Royal College of Surgeons (RCS) rats. METHODS: Three-week-old RCS rats received TES through a contact lens electrode on the left eye weekly for 2 to 6 weeks. The right eyes received sham stimulation on the same days. Electroretinograms (ERGs) were recorded from the rats at 3 weeks (before TES), and at 5, 7, and 9 weeks of age. After the ERG recordings, the rats were killed for morphologic analyses of the retina. RESULTS: Morphologic analyses showed that the mean thickness of the outer nuclear layer (ONL) at each time point was significantly thicker in eyes treated with TES of 100 muA than in eyes with sham stimulation (TES 100 muA versus sham: 5, 7, and 9 weeks of age; P < 0.001). ERG studies showed that TES also significantly preserved retinal function up to 7 weeks of age, but did not preserve retinal function at 9 weeks of age. CONCLUSIONS: TES prolongs the survival of photoreceptors and delays the decrease of retinal function in RCS rats. Although further investigations are necessary before using TES on patients, these findings indicate that TES may be a therapeutic treatment for some patients with diseases of the photoreceptors such as retinitis pigmentosa.

Optical imaging to evaluate retinal activation by electrical currents using suprachoroidal-transretinal stimulation.

PURPOSE: To determine whether reflectance changes of the retina after electrical suprachoroidal-transretinal stimulation (STS) can be detected with a newly developed optical imaging fundus camera. METHODS: Ten eyes of 10 cats were studied. A small retinal area was focally stimulated with electric currents passing between an active electrode placed in the fenestrated sclera and a reference electrode in the vitreous. Biphasic pulses were applied for 4 seconds with a current up to 500 muA. Images of the fundus illuminated with near-infrared (800-880 nm) light were obtained every 20 msec for 26 seconds between 2 seconds before and 20 seconds after the STS. Twenty images of 20 consecutive experiments were averaged. A two-dimensional map of the reflectance changes was constructed by subtracting the images before the stimulation from those after the stimulation. STS-evoked potentials (EPs) were recorded from the optic chiasma. RESULTS: Approximately 0.5 second after the onset of STS, reflectance changes were observed around the retinal locus, where the stimulating electrodes were positioned. The intensity of the reflectance changes was correlated with the intensity of the stimulus current. The area of the reflectance change increased as the current intensity increased and was correlated with the amplitude of the EPs (R(2) = 0.82). CONCLUSIONS: Reflectance changes after STS were localized to the area around the electrode. The strong correlation between the area of the reflectance changes and the amplitude of the EPs suggested that the reflectance changes reflected the activity of retinal neurons elicited by electrical stimulation.

Relationships Between Spatial Contrast Sensitivity and Parafoveal Cone Density in Normal Subjects and Patients With Retinal Degeneration.

BACKGROUND AND OBJECTIVE: To investigate the relationship between spatial contrast sensitivity (CS) and parafoveal cone density (PCD). PATIENTS AND METHODS: Fifteen healthy individuals (mean age: 26.1 years ± 4.5 years) and nine patients with hereditary retinal degeneration (mean age: 31.6 years ± 13.4 years) without media opacities were studied. The CS was measured by CSV-1000 (VectorVision, Greenville, OH). The cone mosaic was photographed with an adaptive optics scanning laser ophthalmoscope (AOSLO) with a 1° × 1° field of view centered on the fovea. The PCD was calculated in an annular area with radii of 0.38° and 0.43°. The CS was converted to the logarithm (logCS), and the area under the logCS function (AULCSF) was determined. RESULTS: The AULCSF was significantly and positively correlated with the PCD in the control (R2 = 0.522; P = .003) and retinal degeneration (R2 = 0.514; P = .03) groups. CONCLUSION: PCD can predict the spatial contrast sensitivity in normal subjects or patients with retinal degeneration without media opacities. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:106-113.].

Xylazine promotes axonal regeneration in the crushed optic nerve of adult rats.

Xylazine, an alpha-2 adrenergic agonist, activates the endogenous trophic factors and neuronal survival signaling. Here, we tested the regenerative effect of xylazine on damaged optic nerve axons in adult rats. After optic nerve crush, xylazine was intraperitoneally injected into three groups of rats: a single administration immediately after the crush, intermittent administration, and daily administration. On day 14, the regenerated axons were quantitatively evaluated by anterograde labeling. Everyday administration but neither single nor intermittent administration markedly increased the number of labeled axons beyond the crush site, with upregulation of growth-associated protein-43 in the ganglion cell layer and the regenerated axons. It was concluded that xylazine promotes axonal regeneration in damaged optic nerves of adult rats.

Attempts to restore visual function after optic nerve damage in adult mammals.

Retinal ganglion cells (RGCs) and their axons, i.e., optic nerve (ON) fibers, provide a good experimental model for research on damaged CNS neurons and their functional ecovery. After the ON transection most RGCs undergo retrograde and anterograde degeneration but they can be rescued and regenerated by transplantation of a piece of peripheral nerve (PN). When the nerve graft was bridged to the visual center, regenerating RGC axons can restore the central visual projection. Behavioral recovery of relatively simple visual function has been proved in such PN-grafted rodents. Intravitreal injections of various neurotrophic factors and cytokines to activate intracellular signaling mechanism of RGCs and electrical stimulation to the cut end of ON have promoting effects on their survival and axonal regeneration. Axotomized RGCs in adult cats are also shown to survive and regenerate their axons through the PN graft. Among the cat RGC types, Y cells, which function as visual motion detector, tend to survive and regenerate axons better than others. X cells, which are essential for acute vision, suffer from rapid death after ON transection but they can be rescued by intravitreal application of neurotrophins accompanied with elevation of cAMP. To restore visual function in adult mammals with damaged optic pathway, the comprehensive and integrative strategies of multiple approaches will be needed, taking care of functional diversity of RGC types.