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Tunable retina encoders for retina implants: why and how.

Current research towards retina implants for partial restoration of vision in blind humans with retinal degenerative dysfunctions focuses on implant and stimulation experiments and technologies. In contrast, our approach takes the availability of an epiretinal multi-electrode neural interface for granted and studies the conditions for successful joint information processing of both retinal prosthesis and brain. Our proposed learning retina encoder (RE) includes information processing modules to simulate the complex mapping operation of parts of the 5-layered neural retina and to provide an iterative, perception-based dialog between RE and human subject. Alternative information processing technologies in the learning RE are being described, which allow an individual optimization of the RE mapping operation by means of iterative tuning with learning algorithms in a dialog between implant wearing subject and RE. The primate visual system is modeled by a retina module (RM) composed of spatio-temporal (ST) filters and a central visual system module (VM). RM performs a mapping 1 of an optical pattern P1 in the physical domain onto a retinal output vector R1(t) in a neural domain, whereas VM performs a mapping 2 of R1(t) in a neural domain onto a visual percept P2 in the perceptual domain. Retinal ganglion cell properties represent non-invertible ST filters in RE, which generate ambiguous output signals. VM generates visual percepts only if the corresponding R1(t) is properly encoded, contains sufficient information, and can be disambiguated. Based on the learning RE and the proposed visual system model, a novel retina encoder (RE*) is proposed, which considers both ambiguity removal and miniature eye movements during fixation. Our simulation results suggest that VM requires miniature eye movements under control of the visual system to retrieve unambiguous patterns P2 corresponding to P1. For retina implant applications, RE* can be tuned to generate optimal ganglion cell codes for epiretinal stimulation.

Action Potentials↗

Use of retroillumination to visualize optical aberrations caused by tear film break-up.

PURPOSE: The aim of the current study was to develop quantitative methods to assess optical aberrations caused by tear film disruption. METHODS: We used standard fluorescein imaging (FL) and a novel retroillumination (RI) method to image tear film disruption in 12 eyes. Using a clinical slit lamp biomicroscope, we alternated between widefield blue and narrow-beam white light to obtain an interleaved series of FL and RI images of the time course and pattern of tear film break-up. We developed an optical analysis that indicates that the RI image should be proportional to the spatial derivative of the FL image. Intensity fluctuations in the RI images are due to thickness changes in the tear film, whereas intensity fluctuations in FL images are directly determined by tear film thickness. RESULTS: As predicted by optical analysis of RI, the spatial distribution of gaps in the tear film seen with fluorescein appeared as pairs of light and dark contours in the RI images, and a precise correspondence between the spatial derivative of the FL image (slope) and the RI image was found. Both methods showed a gradual spreading of the tear disruption during blink suppression that varied tremendously among eyes in both time and spatial pattern. Resumption of normal blinking did not produce an immediate reconstitution of the normal tear film, and areas of tear break-up created during blink suppression remained abnormal for up to several minutes of normal blinking. CONCLUSIONS: Our analysis indicates that both FL and RI have the potential to quantify optical changes occurring during tear break-up. These results support an interpretation of RI as an intensity-based method for mapping the highly irregular optical aberrations of the eye produced by tear film disruption.

Adult↗

Competitive and positional cues in the patterning of nerve connections.

The visual system of lower vertebrates has served as an important testing ground for the mechanisms that generate topographic neuronal connections. During both the outgrowth and the regeneration of the optic nerve, a smoothly ordered map of the retina is formed on its major target, the optic tectum (the retinotectal projection). Experiments performed on this projection have offered support for a variety of mechanisms, including the matching of positional cues in the retina and tectum, the guidance of nerve fibers by interactions between fibers, competition for synaptic space, and the refinement of connections based on neuronal activity. Unfortunately, individual experiments that support any one of these mechanisms have been taken at times as evidence against the involvement of any other mechanism; for example, experiments demonstrating the importance of positional cues have been thought mistakenly to indicate that activity-based interactions are unimportant. Computer simulations, in which multiple, somewhat opposed, mechanisms are allowed to operate in concert demonstrate that such a hybrid model is able to generate a full range of experimental results. More importantly, the elimination of any one of the mechanisms renders the model unable to fit entire classes of findings. Thus, the patterning of the retinotectal projection is best viewed as a process in which the optic nerve terminals attempt to satisfy multiple constraints in selecting their target sites.

Animals↗

Retroviral misexpression of engrailed genes in the chick optic tectum perturbs the topographic targeting of retinal axons.

We have investigated the role of the homeodomain transcription factor genes En-1 and En-2, homologs of the Drosophila segment polarity gene engrailed, in regulating the development of the retinotopic map in the chick optic tectum. The En proteins are distributed in a gradient along the rostral-caudal axis of the developing tectum, with highest amounts found caudally. Previous evidence suggests that En-1 and En-2 may regulate the polarity of the rostral-caudal axis of the tectum and the subsequent topographic mapping of retinal axons. We have tested this hypothesis by using a recombinant replication-competent retrovirus to overexpress the En-1 or En-2 genes in the developing tectum. Anterograde labeling with the axon tracer Dil was used to analyze the topographic mapping of retinal axons after the time that the retinotectal projection is normally topographically organized. Overexpression of either En-1 or En-2 perturbed the topographic targeting of retinal axons. In En-infected tecta, nasal retinal axons form an abnormally diffuse projection with numerous aberrant axons, branches, and arbors found at topographically incorrect locations, colocalized with domains of viral infection. In contrast, temporal axons did not form a diffuse projection or discrete aberrant arbors; however, many temporal axons were stunted and ended aberrantly rostral to their appropriate TZ, or in other cases either did not enter the tectum or formed a dense termination at its extreme rostral edge. These findings indicate that En-1 and En-2 are involved in regulating the development of the retinotopic map in the tectum. Furthermore, they support the hypothesis that En genes regulate the polarity of the rostral-caudal axis of the tectum, most likely by controlling the expression of retinal axon guidance molecules.

Animals↗

Neural maps of head movement vector and speed in the optic tectum of the barn owl.

1. This study investigates the contribution of the optic tectum in encoding the metric and kinetic properties of saccadic head movements. We describe the dependence of head movement components (size, direction, and speed) on parameters of focal electrical stimulation of the barn owl's optic tectum. The results demonstrate that both the site and the amount of activity can influence head saccade metrics and kinetics. 2. Electrical stimulation of the owl's optic tectum elicited rapid head movements that closely resembled natural head movements made in response to auditory and visual stimuli. The kinetics of these movements were similar to those of saccadic eye movements in primates. 3. The metrics and kinetics of head movements evoked from any given site depended strongly on stimulus parameters. Movement duration increased with stimulus duration, as did movement size. Both the size and the maximum speed of the movement increased to a plateau value with current strength and pulse rate. Movement direction was independent of stimulus parameters. 4. The initial position of the head influenced the size, direction, and speed of movements evoked from any given site: when the owl initially faced away from the direction of the induced saccade, the movement was larger and faster than when the owl initially faced toward the direction of the induced movement. 5. A characteristic movement of particular size, direction, and speed could be defined for each site by the use of stimulation parameters that elicited plateau movements with normal kinetic profiles and by having the head initially centered on the body. The size, direction, and speed of these characteristic movements varied systematically with the site of stimulation across the tectum. The map of head movement vector (size and direction) was aligned with the sensory representations of visual and auditory space, such that the movement elicited from a given site when the owl initially faced straight ahead brought the owl to face that region of space represented by the sensory responses of the neurons at the site of stimulation. 6. The results imply that both the site and the amount of neural activity in the optic tectum contribute to encoding the metrics and kinetics of saccadic movements. A comparison of the present findings with previous studies on saccadic eye movements in primates and combined eye and head movements in cats suggests striking similarities in the ways in which tectal activity specifies a redirection in gaze to such dissimilar motor effectors as the eyes and head.

Animals↗

Gene structure and chromosomal localization of mouse Opa1 : its exclusion from the Bst locus.

BACKGROUND: Autosomal dominant optic atrophy type 1 (DOA) is the most common form of hereditary optic atrophy in human. We have previously identified the OPA1 gene and shown that it was mutated in patients with DOA. OPA1 is a novel member of the dynamin GTPase family that play a role in the distribution of the mitochondrial network. The Bst (belly spot and tail) mutant mice show atrophy of the optic nerves and previous mapping data raise the possibility that Bst and OPA1 are orthologs. In order to analyse the Bst mouse as a model for DOA, we therefore characterized mouse Opa1 and evaluated it as a candidate for the Bst mutant mouse. RESULTS: Comparison of mouse and human OPA1 sequences revealed 88% and 97% identity at the nucleotide and amino acid levels, respectively. Presence of alternatively spliced mRNAs as seen in human was conserved in the mouse. Screening of the whole mRNA coding sequence and of the 31 exons of Opa1 did not reveal any mutation in Bst. Using a radiation hybrid panel (T31), we mapped Opa1 to chromosome 16 between genetic markers D16Mit3 and D16Mit124, which is 10 cM centromeric to the Bst locus. CONCLUSION: On the basis of these results we conclude that Opa1 and Bst are distinct genes and that the Bst mouse is not the mouse model for DOA.

Animals↗

Detection and Mapping of Decoupled Stellar and Ionized Gas Structures in the Ultraluminous Infrared Galaxy IRAS 12112+0305.

Integral field optical spectroscopy with the INTEGRAL fiber-fed system and Hubble Space Telescope optical imaging are used to map the complex stellar and warm ionized gas structure in the ultraluminous infrared galaxy IRAS 12112+0305. Images reconstructed from wavelength-delimited extractions of the integral field spectra reveal that the observed ionized gas distribution is decoupled from the stellar main body of the galaxy, with the dominant continuum and emission-line regions separated by projected distances of up to 7.5 kpc. The two optical nuclei are detected as apparently faint emission-line regions, and their optical properties are consistent with being dust-enshrouded weak [O i] LINERs. The brightest emission-line region is associated with a faint (mI=20.4), giant H ii region of 600 pc diameter, in which a young ( approximately 5 Myr) massive cluster of about 2x107 M middle dot in circle dominates the ionization. Internal reddening toward the line-emitting regions and the optical nuclei ranges from 1 to 8 mag in the visual. Taking the reddening into account, the overall star formation in IRAS 12112+0305 is dominated by starbursts associated with the two nuclei and corresponds to a star formation rate of 80 M middle dot in circle yr-1.

Journal Article↗

Structure and function in glaucoma: The relationship between a functional visual field map and an anatomic retinal map.

PURPOSE: To examine the relationship between an anatomic map relating the retinal nerve fiber layer (RNFL) distribution to the optic nerve head and a functional map derived from the interpoint correlation of raw sensitivities in visual field (VF) testing. METHODS: Previously, interpoint correlations were generated for all possible pairs of VF test points in a dataset of 98,821 Humphrey VF test results taken from the Moorfields Eye Hospital archive. The relationship between these correlations and the physical distance between the VF test point pairs was evaluated by Pearson's correlation coefficient and multiple regression analysis. The distance between the pairs of VF test points was calculated in two ways. First, the anatomic map was used to estimate the angular distance at the optic nerve head (ONH), between the RNFL bundles corresponding to the VF test points in each pair (ONHd). Second, the retinal distance between pairs of test points was calculated from the Humphrey VF template (RETd). A best-fit model for predicting functional correlation (FC) from ONHd and RETd was constructed and used to formulate a filter incorporating the anatomic-functional correlation data. RESULTS: All scatterplots showed a negative association between interpoint retinal sensitivity correlation values and distance between points: ONHd (R2 = 0.60) and RETd (R2 = 0.33). The raw sensitivity correlation values could be predicted from a multiple regression model using ONHd, RETd, and a combined interaction of ONHd and RETd (R2 = 0.75, P < 0.00001). The construction of a new filter was based on the equation FC = 0.9325 - (0.0029 . ONHd) - (0.0077 . RETd) + (0.0001 . ONHd . RETd). CONCLUSIONS: A good level of association was observed between the strength of correlation between points in the VF and the relative location of those test points in the peripheral retina and in corresponding RNFL bundles at the ONH. These results help to validate the relationship between structure and function and may be of use in the further refinement of physiologically derived VF filters to reduce measurement noise.

Glaucoma, Open-Angle↗

Corneal topography using the Holladay Diagnostic Summary.

PURPOSE: To describe new software developments in videokeratography and illustrate their application in patients with corneal disease or patients who have had keratorefractive surgery. METHODS: The Holladay Diagnostic Summary provides 4 maps and 15 corneal parameters for the clinician. The maps include 2 refractive power maps on standard and auto scales, a profile difference map for determining the corneal shape relative to normal asphericity, and a distortion map to display the optical quality of the cornea. The 15 corneal parameters provide quantitative information about the cornea for a 3.0 mm pupil; e.g., effective refractive power, regular astigmatism, asphericity, and predicted corneal acuity. The maps and parameters are used to analyze a calibration ball and five clinical examples. RESULTS: Patients with diseases such as keratoconus or patients who have had keratorefractive surgery have characteristic changes in the 4 maps and the 15 corneal parameters. CONCLUSION: When true refractive power maps, a profile difference map, a distortion map, and 15 corneal parameters are analyzed, characteristic changes are found that can help clinicians recognize and monitor corneal disease and refractive surgery and correlate these changes with patients' visual symptoms.

Adult↗

Stroboscopic illumination and dark rearing block the sharpening of the regenerated retinotectal map in goldfish.

Blocking activity with intraocular tetrodotoxin prevents the sharpening of the retinotectal map formed during regeneration of the optic nerve. If (under normal conditions) the initially diffuse map sharpens because of correlated activity in neighboring but not distant ganglion cells, then sharpening should also be prevented merely by disrupting the spatiotemporal correlation in the pattern of activity. To test this idea, fish were exposed during regeneration to stroboscopic illumination in a featureless environment, or were maintained in complete darkness. The regenerating cells remained visually responsive after axotomy, and the xenon strobe effectively drove each ganglion cell at a constant latency. The maps formed in the strobe-reared fish were normally oriented, but the multiunit receptive fields were greatly enlarged, averaging 32 degrees. In control regenerates, multiunit receptive fields averaged only 11-12 degrees, nearly the same as for single units. Dark rearing, which allows only spontaneous activity, also resulted in enlarged multiunit receptive fields, averaging more than 28 degrees. Both effects parallel those reported previously with tetrodotoxin block. The mature projection did not become diffuse as a result of the strobe rearing, and the sensitive period corresponded to the early stage of synaptogenesis (20-34 days). Periods of normal visual exposure after 35 days produced very little sharpening of the diffuse maps produced during either strobe or dark rearing. The results are attributed to an activity-dependent stabilization of developing synapses. The correlated firing of neighboring ganglion cells could allow postsynaptic summation of their responses, and the retention of those more effective, retinotopically placed synapses might then occur via a Hebbian mechanism.

Animals↗

Novel functional imaging technique from brain surface with optical coherence tomography enabling visualization of depth resolved functional structure in vivo.

Mapping of the activity of brain by optical intrinsic signal imaging (OISI) provides a two-dimensional activation pattern of visual cortical areas at a resolution of a few hundred microns. However, integration of the intrinsic signal over depth results in loss of finer information about functional organization across the depth. Here, we report the first successful implementation of optical coherence tomography (OCT) at around 30 microm depth resolution to investigate cortical functions of a cat brain in vivo. This technique, named functional OCT (fOCT) provided visually evoked changes in the OCT signal. The fOCT signal shows stimulus specificity that correlates well with that of the intrinsic signals and provides depth resolved layer specific functional information.

Animals↗

Different anisotropies of movement direction in upper and lower layers of the cat's area 18 and their implications for global optic flow processing.

Cells in Area 18 of awake and behaving cats were tested for directional preference with a large visual noise pattern. Upper and lower layer cells were found to exhibit different anisotropies for movement direction, offset by 90 degrees. These findings could reflect different functions for the global mapping and processing of optic flow field in upper and lower layers.

Animals↗

Cytological mapping of Om mutants of Drosophila ananassae.

Semidominant, optic morphology (Om) mutants in Drosophila ananassae have been genetically mapped to at least 25 loci throughout the genome (Hinton, 1984; 1988). Among them, four X-linked Om mutants were proved to be associated with the insertion of a transposable element, tom (Shrimpton et al., 1986; Tanda et al., 1988). In the present study, cytological mapping of autosomal Om mutants was carried out by in situ hybridization to polytene chromosomes using a cloned tom element as a probe. The cytological site for each autosomal Om mutant has been determined to a single band of the salivary gland chromosomes.

Animals↗

Fast axonally transported proteins in regenerating goldfish optic nerve: effect of abolishing electrophysiological activity with TTX.

Blocking neural activity with intraocular tetrodotoxin (TTX) hinders regeneration of goldfish optic axons, and prevents the refinement of the retinotopic map that is formed in the optic tectum. The latter effect is not observed with TTX treatment confined to the first two weeks of regeneration, but is produced when the TTX treatment is delayed until after this time. In the present study, 2-dimensional gel electrophoresis was used to analyse the effects of two different schedules of TTX treatment (0-9 days or 14-32 days) on incorporation of [3H]proline into individual proteins conveyed by fast axonal transport in the optic nerve. The labelling of many of these proteins was somewhat reduced by either schedule of TTX treatment, but a number of proteins showed a larger reduction as a result of the delayed treatment. These included some glycoproteins, as well as a protein of about 45 kDa and pI 4.5, which shows greatly increased synthesis during regeneration, and which is probably identical to the 'growth-associated protein' GAP-43. By contrast, cytoskeletal proteins (alpha- and beta-tubulin and actin) were unaffected by the delayed TTX treatment. It is possible that the differential effects of the early and delayed TTX treatments on various transported proteins may account for differences in the effect of these treatments on the retinotectal projection.

Animals↗

Antibodies to ependymin block the sharpening of the regenerating retinotectal projection in goldfish.

The regenerating optic nerve of goldfish first reestablishes a rough retinotopic map on the tectum, then goes through an activity dependent refinement that appears to involve the elimination of inappropriate branches from early regenerated arbors. Retinotopically appropriate branches and synapses may be stabilized because the normally correlated firing of neighboring ganglion cells could cause summation of their postsynaptic responses, making them more effective. Thus, refinement of the map may be similar in several ways to associative learning. In this study, we therefore tested whether ependymin, a major protein component of the extracellular fluid that has been implicated in synaptic changes thought to be associated with learning a simple task in goldfish, may also be involved in refinement of the retinotopic map. Goldfish that had undergone unilateral optic nerve crush received intraventricular infusion of antiependymin IgG or of control IgG's beginning at 21 days postcrush. Tectal recordings from these fish at 39-56 days postcrush showed that the projection had failed to sharpen, much as in the fish with activity blocked or synchronized; the average size of the multiunit receptive fields was 31 degrees vs 11 degrees normally. The field potentials elicited from these tecta by optic nerve shock were not significantly smaller than in controls, suggesting normal levels of synaptogenesis. Control projections, identically treated but infused with either unrelated IgG or Ringer's alone regenerated normally, giving multiunit receptive fields of 12 degrees. Intact (non-regenerating) projections of the experimental fish were not rendered abnormal by the IgG treatment. Histology showed the retinas and tecta of the infused fish to be normal in appearance. The results show a specific block of sharpening by antiependymin IgG. The ependymal glia of the tectum stain positively for ependymin in normal fish, particularly the cell bodies in the ependymal layer. The tectum, particularly the ependymal layer, stains more intensely during regeneration, which appears to trigger increased synthesis of ependymins in the ependymal glia. This increase and the block of sharpening by specific antibodies to ependymin suggest a possible role for ependymin in activity dependent synaptic stabilization, possibly through its polymerization when calcium is focally depleted at active synapses.

Action Potentials↗

Stress-mapping sensors for high-power adaptive micro-optics.

Continuous deformable membrane mirrors are becoming more attractive for use in adaptive optics because they cause no diffraction in the reflected beam and ensure smooth and continuous phase variations across the mirrors. However, when such mirrors are used to correct a high-power incident wave front, the absorption in the coatings causes the temperature of the membrane to increase, thereby creating in-plane thermal stress due to the rigidly clamped boundaries. We present a technique to measure thermal stress in such nondeforming membrane structures. The directional stress and temperature effects are simultaneously measured and decoupled in micromachined membrane mirrors by using a group of three ion-implanted silicon resistors with different orientations. In stress measurements made with incident power, the sensors measure changes in compressive thermal stress to within 80-90 kPa.

Journal Article↗

Local observation and spectroscopy of optical modes in an active photonic-crystal microcavity.

We report the direct, room-temperature, near-field mapping and spectroscopy of the optical modes of a photonic-crystal microcavity containing quantum wells. We use a near-field optical probe to reveal the imprint of the cavity mode structure on the quantum-well emission. Furthermore, near-field spectroscopy allows us to demonstrate the strong spatial and spectral dependence of the coupling between the sources and the microcavity. This knowledge will be essential in devising future nanophotonic devices.

Journal Article↗

Quantitative MR temperature monitoring of high-intensity focused ultrasound therapy.

A new quantitative method has been developed for real-time mapping of temperature changes induced by high intensity focused ultrasound (HIFU). It is based on the temperature dependence of the T1 relaxation time and the equilibrium magnetization. To calibrate the temperature measurement, the functional relationship between T1 and temperature was examined in different samples of porcine muscle and fatty tissue. The method was validated by a comparison of calculated temperature maps with fiber-optic measurements in heated muscle tissue. The experiment showed that the accuracy of the MR method for temperature measurements is better than 1 degree C. Since the acquisition time of the employed MR sequence takes only 3 s per slice and the calculation of the temperature map can be performed within seconds, the imaging technique works nearly in real-time. The temperature measurement could be realized during HIFU showing no disturbances by ultrasound sonication. In comparison to other MR approaches, the advantages of the introduced method lie in a sufficient accuracy and time resolution combined with a reasonable robustness against motion as well as the feasibility for temperature monitoring in fatty tissues.

Adipose Tissue↗