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PubMed1977

The central projections in the retina in Necturus maculosus.

The projections of the retina in Necturus maculosus were studied by injecting radioactive proline into one eye. Labeling was seen in both the contralateral and ipsilateral diencephalon and tectum. The contralateral fibers are divided into three major tracts: the marginal, axial, and basal. The ipsilateral fibers separate into a marginal and an axial optic tract. The contralateral and ipsilateral axial optic tracts have a similar distribution. The contralateral and ipsilateral marginal optic tracts projecting to the diencephalon also have a similar distribution. However, in the tectum the ipsilateral marginal optic tract ends in the anterior third while the contralateral extends almost the entire length of the tectum. The retinotectal ipsilateral projection ends in clumps as has been described in other vetebrates. A direct ipsilateral retinotectal projection has not been described in any other amphibian.

Animals↗

PubMedDate not supplied

[A case or Leber hereditary optic neuropathy (LHON): differential diagnosis with post inflammatory atrophy of nerve II using the mtDNA analysis].

The Leber hereditary optic neuropathy (LHON) is a disease due to a mtDNA mutation. The disorder results from enzymatic perturbations in the mitochondrial respiratory chain. Clinically the LHON may present as a progressive axonal atrophy of the optic nerves with or without other neurological symptoms. The process of reaching the diagnosis of the LHON by means of the molecular analysis of mtDNA is discussed.

Adult↗

PubMed2005

Photoemission electron microscopy as a tool for the investigation of optical near fields.

Photoemission electron microscopy was used to image the electrons photoemitted from specially tailored Ag nanoparticles deposited on a Si substrate (with its native oxide SiO(x)). Photoemission was induced by illumination with a Hg UV lamp (photon energy cutoff homega(UV) = 5.0 eV, wavelength lambda(UV) = 250 nm) and with a Ti:sapphire femtosecond laser (homega(l) = 3.1 eV, lambda(l) = 400 nm, pulse width below 200 fs), respectively. While homogeneous photoelectron emission from the metal is observed upon illumination at energies above the silver plasmon frequency, at lower photon energies the emission is localized at tips of the structure. This is interpreted as a signature of the local electrical field therefore providing a tool to map the optical near field with the resolution of emission electron microscopy.

Journal Article↗

PubMed2001

Near-field coherent spectroscopy and microscopy of a quantum dot system.

We combined coherent nonlinear optical spectroscopy with nano-electron volt energy resolution and low-temperature near-field microscopy with subwavelength resolution (<lambda/2) to provide direct and local access to the excitonic dipole in a semiconductor nanostructure quantum system. Our technique allows the ability to address, excite, and probe single eigenstates of solid-state quantum systems with spectral and spatial selectivity while simultaneously providing a measurement of all the various time scales of the excitation including state relaxation and decoherence rates. In analogy to scanning tunneling microscopy measurements, we can now map the optical local density of states of a disordered nanostructure. These measurements lay the groundwork for studying and exploiting spatial and temporal coherence in the nanoscopic regime of solid-state systems.

Journal Article↗

PubMed1976

Regional specialization in the golden hamster's retina.

Ganglion cell swere counted and measured in whole mounts of the hamster's retina, stained with methylene blue. Their density varies between about 1,000/mm2 at the edge of the retina to about 5-6,000/mm2 in a broad area centralis centred about 1.9 mm(39 deg) directly temporal to the optic disk. Maps of cell density show a long horizontal extension of the dense area in the nasal direction. The sizes of ganglion cell somata fall into two main groups--small cells (5-11 mum diameter) and large cells (greater than 11 mum), the latter including a small proportion of giant cells (greater than 17 mum). All three classes of cells are maximal in density in the area centralis, although the small cells are relatively more numerous there. The total number of cells is about 114,000 with about 63,000 small cells and about 51,000 large. The optic nerve contains about 69,000 unmyelinated axons and about 50,000 myelinated axons, suggesting that the latter are the fibres of the larger ganglion cells. It is likely that the projections of the centres of the areae centrales of the two eyes are normally divergent in space; they are therefore not on "corresponding retinal points."

Animals↗

PubMed2005

Changes in cytochrome oxidase in the piriform cortex after status epilepticus in adult rats.

PURPOSE: The piriform cortex is involved in genesis and propagation of temporal lobe seizures. Degenerating neurons demonstrated by FluoroJade B staining are visible early after status epilepticus (SE) as well as after longer intervals. Furthermore, the piriform cortex is activated during an early phase of experimental temporal seizures, as described by magnetic resonance imaging (MRI) studies. It indicates that the early activity of the piriform cortex should be accompanied by increased adenosine triphosphate (ATP) production. Cytochrome oxidase activity in the brain may be used as an endogenous metabolic marker for neurons. The present research studied activity of the cytochrome oxidase separately in the rostral and caudal parts of the piriform cortex after lithium chloride-pilocarpine-induced SE in adult rats. METHODS: SE was induced by a single dose of pilocarpine (40 mg/kg) in LiCl-pretreated adult Wistar rats. Cytochrome oxidase activity was mapped by optical density on sections stained with histochemistry separately in the rostral and caudal parts of the piriform cortex. RESULTS: Optical density of the rostral part of the piriform cortex remained nearly unchanged at both 1 week (0.284 +/- 0.009 in SE group vs. 0.297 +/- 0.005 in controls) and 3 months (0.318 +/- 0.007 in SE group vs. 0.333 +/- 0.004 in controls) after SE intervals. The caudal part of the piriform cortex showed a decrease of optical density in both groups at 1 week (0.265 +/- 0.007 in SE group vs. 0.285 +/- 0.009 in controls) and 3 months after SE (0.292 +/- 0.006 in SE animals vs. 0.310 +/- 0.003 in controls), respectively. Nissl-stained sections demonstrated a marked neuronal loss and gliosis and/or necrotic cavities through the caudal piriform cortex 1 week after SE. CONCLUSIONS: Our results demonstrated that damage of the piriform cortex is not homogeneous and thus that its parts are differently involved in epileptic activity.

Animals↗

PubMed2005

Optic radiation changes after optic neuritis detected by tractography-based group mapping.

Postmortem data suggest that trans-synaptic degeneration occurs in the lateral geniculate nucleus after optic nerve injury. This study investigated in vivo the optic radiations in patients affected by optic neuritis using fast marching tractography (FMT), a diffusion magnetic resonance imaging (MRI) fiber tracking method, and group mapping techniques, which allow statistical comparisons between subjects. Seven patients, 1 year after isolated unilateral optic neuritis, and ten age and gender-matched controls underwent whole-brain diffusion tensor MR imaging. The FMT algorithm was used to generate voxel-scale connectivity (VSC) maps in the optic radiations in each subject in native space. Group maps of the left and right optic radiations were created in the patient and control group in a standardized reference frame using statistical parametric mapping (SPM99). The reconstructed optic radiations in the patient group were localized more laterally in the posterior part of the tracts and more inferiorly than in the control group. Patients showed reduced VSC values in both tracts compared with controls. These findings suggest that the group mapping techniques might be used to assess changes in the optic radiations in patients after an episode of optic neuritis. The changes we have observed may be secondary to the optic nerve damage.

Adult↗

PubMed1998

[Diagnostic error in Leber's optic neuropathy. Value of clinical and molecular genetic studies].

BACKGROUND: Leber's hereditary optic neuropathy is associated with point mutations in the mitochondrial DNA (mtDNA) that appear to be pathogenic for this disease. These mutations affect nucleotide positions 3460, 11,778 and 14,484. MATERIALS AND METHODS: We reviewed the clinical and molecular genetic characteristics of 29 visually symptomatic patients with the clinical diagnosis of LHON. RESULTS: Nine patients really suffered from LHON, but in 20 patients other ocular diseases could be proven. Degeneration of the retina and choroid was most common (seven patients), followed by vascular optic disease (six patients). Three patients suffered from tobacco-alcohol amblyopia, two from optic neuritis and two from autosomal dominant optic neuropathy. CONCLUSIONS: The clinical diagnosis of LHON is strengthened by a proven maternal inheritance and clinical signs such as a severe decrease in visual acuity, central or centrocecal scotomas in the perimetry and pseudoedema of the optic disc, followed by optic atrophy. Pathognomonic clinical signs of LHON are twisted vessels and ectatic capillaries in the fundus of these patients and their relatives of the maternal line, i.e., peripapillary microangiopathy. A careful analysis of the patients' pedigrees, anamnesis and the functional and morphological results of the clinical examinations helps to avoid misdiagnosis of the disease. However, the expensive and time-consuming molecular genetic analysis is always necessary to confirm or exclude the diagnosis of LHON.

Adult↗

PubMed1995

[Molecular genetic analysis of Leber's hereditary optic neuropathy with the 3460 mutation in Japanese pedigrees].

We have identified a point mutation at nucleotide position 3460 in the ND1 gene of complex I in a Japanese pedigree with Leber's hereditary optic neuropathy by sequencing the ND genes in mitochondrial DNA. None of the 60 healthy Japanese had the 3460 mutation. The proband and his mother also had the 7444 mutation in the COI gene of complex IV and became nearly blind at age 19 with visual acuities of 0.02 OD and 0.04 OS We screened 30 patients with bilateral optic atrophy for the 3460 mutation, and identified one male patient who had the 3460 mutation in heteroplasmic fashion without carrying the 7444 mutation. He lost his sight at age 14 but it recovered to 1.2 OD and 0.7 OS about two years and half after the onset. The difference in final visual acuity between these two patients may reflect the degree of reduction in mitochondrial energy production.

Adolescent↗

PubMed2002

Three-dimensional, Bayesian image reconstruction from sparse and noisy data sets: near-infrared fluorescence tomography.

A method for inverting measurements made on the surfaces of tissues for recovery of interior optical property maps is demonstrated for sparse near-infrared (NIR) fluorescence measurement sets on large tissue-simulating volumes with highly variable signal-to-noise ratio. A Bayesian minimum-variance reconstruction algorithm compensates for the spatial variability in signal-to-noise ratio that must be expected to occur in actual NIR contrast-enhanced diagnostic medical imaging. Image reconstruction is demonstrated by using frequency-domain photon migration measurements on 256-cm(3) tissue-mimicking phantoms containing none, one, or two 1-cm(3) heterogeneities with 50- to 100-fold greater concentration of Indocyanine Green dye over background levels. The spatial parameter estimate of absorption owing to the dye was reconstructed from only 160 to 296 surface measurements of emission light at 830 nm in response to incident 785-nm excitation light modulated at 100 MHz. Measurement error of acquired fluence at fluorescent emission wavelengths is shown to be highly variable. Convergence and quality of image reconstructions are improved by Bayesian conditioning incorporating (i) experimentally determined measurement error variance, (ii) recursively updated estimates of parameter uncertainty, and (iii) dynamic zonation. The results demonstrate that, to employ NIR fluorescence-enhanced optical imaging for large volumes, reconstruction approaches must account for the large range of signal-to-noise ratio associated with the measurements.

Analysis of Variance↗

PubMed1999

Mapping membrane potential transients in crayfish (Procambarus clarkii) optic lobe neuropils with voltage-sensitive dyes.

Voltage-sensitive dyes NK 2761 and RH 155 were employed (in conjunction with a 12 x 12 photodiode array) to study membrane potential transients in optic lobe neuropils in the eye stalk of the crayfish Procambarus clarkii. By this means we investigated a pathway linking deutocerebral projection neurons, via hemiellipsoid body local interneurons, to an unidentified target (most likely neurons processing visual information) in the medulla terminalis. Rapid (10- to 20-ms duration), transient changes in absorption with the characteristics of action potentials were recorded from the optic nerve and the region occupied by deutocerebral projection neurons after stimulation of the olfactory globular tract in the optic nerve and were blocked by 1 microM tetrodotoxin. Action potentials appeared to propagate to the glomerular layer of the hemiellipsoid body where synaptic responses were recorded from a restricted region of the hemiellipsoid body occupied by dendrites of hemiellipsoid body neurons. Action potentials were also recorded from processes of hemiellipsoid body neurons located in the medulla terminalis. Synaptic responses in the hemiellipsoid body and medulla terminalis were eliminated by addition to the saline of 500 microM Cd2+ or 20 mM Co2+, whereas the action potential attributed to branches of deutocerebral projection neurons in the hemiellipsoid body remained unaffected. Action potentials of hemiellipsoid body neurons in the medulla terminalis evoked postsynaptic potentials (50- to 200-ms duration) with an unidentified target in the medulla terminalis. Transient absorption signals were not detected in either the internal or external medulla nor were they recorded from other parts of the optic lobes in response to electrical stimulation of axons of the deutocerebral projection neurons. Functional maps of optical activity, together with electrophysiological and pharmacological findings, suggest that gamma-aminobutyric acid affects synaptic transmission in glomeruli of the hemiellipsoid body. Synapses of the olfactory pathway located in the medulla terminalis may act as a "filter," modifying visual information processing during olfactory stimulation.

Animals↗

PubMed1984

The representation of the visual field in parvicellular and magnocellular layers of the lateral geniculate nucleus in the macaque monkey.

Two-dimensional maps of individual layers of the dorsal lateral geniculate nucleus (LGN) in the macaque monkey were constructed and used as a basis for comparing laminar size, shape, and topographic organization. Topographical data from the electrophysiological investigation of the LGN by Malpeli and Baker ('75) were displayed on maps of all six layers. As known from previous studies, there is a significant over-representation of central vision in the LGN. Unexpectedly, though, the visual representation is anisotropic over portions of most LGN layers. That is, the linear magnification factor (millimeters along the laminar surface per degree of visual field) is not equal for all directions from a given point in the visual field. Moreover, the visual representations in the parvicellular and magnocellular divisions of the LGN differ both in their emphasis on central vision and in their anisotropies. To determine the degree of individual variability, laminar maps were prepared from the LGN of seven other hemispheres. The shapes of laminar maps varied considerably between LGNs, from nearly circular to highly elliptical, but the surface area was relatively constant for each layer. Topographical organization, determined by mapping the optic disc representation on the LGN laminae and by labeling from anterograde and retrograde tracer injections in striate cortex, showed significant individual variability. Interestingly, the visual representations in the LGN and striate cortex are topologically inverted with respect to one another. This indicates that the establishment of geniculocortical connections involves a systematic crossing-over of fibers. Information on cell densities and magnification factors in striate cortex obtained from other studies was compared to the results of the present study in order to estimate ratios of cortical neurons to LGN neurons at different eccentricities. The total number of cortical neurons per LGN neuron is about 130 on average, but it extends over approximately a tenfold range, from less than 100 in the far periphery to nearly 1,000 in the fovea. The estimated number of cells in layers 4A and 4C beta per parvicellular layer neuron is smaller and extends over a slightly narrower range, from 30 to 240, whereas the number of layer 4C alpha neurons per magnocellular neuron varies more widely, from about 45 to 7,000.

Animals↗

PubMed1999

[Leber optic neuropathy in women and children].

BACKGROUND: Leber's hereditary optic neuropathy is associated with point mutations in the mitochondrial DNA (mtDNA) that appear to be pathogenetic for this disease. These mutations affect nucleotide positions 3460, 11778 and 14484. Does the clinical course of LHON differ between men, women and children? MATERIALS AND METHODS: We reviewed the clinical and molecular genetic characteristics of 15 visually symptomatic patients with the clinical diagnosis of LHON (11 women and 4 male children) and compared them with 66 men with LHON. RESULTS: LHON was confirmed clinically and with molecular genetic methods in all cases. Men, women and children showed no differences: Classic fundus findings and typical visual field defects were equally found in both sexes. However, age at the beginning of the disease, severity of LHON and rate of spontaneous recovery differed between groups. Women were older (19-55 years, average 31.3 years) than men (15-53 years, average 24.3 years) at the beginning of the disease. Women suffered more severely from LHON. Spontaneous recovery of vision in women was extremely rare. Many more women had a LHON-affected mother than men. All the affected children (9-14, average 11.7 years at the beginning of the disease) did not have a good visual outcome. CONCLUSIONS: There are some differences in the course of LHON between men and women, concerning age, severity of LHON and rate of spontaneous recovery. Children may also have an unfavorable prognosis.

Adolescent↗

PubMed1995

[Correlation between clinical and molecular genetic findings in Leber's optic atrophy].

Leber's hereditary optic neuropathy (LHON) is associated with point mutations of mitochondrial DNA (mtDNA) that appear to be pathogenetic for this disease. These mutations affect nucleotide positions 3460, 4160, 11,778, 14,484, and possibly 15,257. The pathogenetic significance of other mtDNA point mutations (secondary mutations) is less clear. We reviewed the clinical and molecular genetic characteristics of 29 visually symptomatic patients from 26 families. In addition, we studied 54 relatives of the maternal line of these patients. Sixteen of them underwent clinical and molecular genetic examination; 38 underwent only molecular genetic examination. The 29 affected individuals showed a male predominance of 93.1% (27/29) and ages of onset of visual loss ranging from 15 to 55 years. The time interval between affected eyes was never longer than 1 year. Tobacco and/or alcohol abuse was common. Peripapillary microangiopathy was found in 20.7% (6/29) of our patients. The number of patients with peripapillary microangiopathy seems to be small, but we could not examine all patients early after onset of the disease: the time of first examination is critical for the diagnosis of peripapillary microangiopathy. From the 16 relatives who underwent clinical examination, 62.5% (10/16) also had peripapillary microangiopathy. Eighteen patients were analyzed by brain computed tomography or magnetic resonance imaging. Four definitely pathological results seem remarkably high in comparison with the results of other authors. Our LHON patients and their relatives invariably had an identical pattern of point mutations, both primary as well as secondary. Of the LHON patients, 79.3% had the primary mutation at position 11,778, 20.7% at position 3460. Different numbers and combinations of secondary mutations were observed in a large portion of both groups. Three patients with the 11,778 mutation noticed remarkable visual recovery. There was no clear correlation between the type and number of point mutations in the individual and the severity of the disease.

Adolescent↗

PubMed1999

Responses of contralateral SI and SII in cat to same-site cutaneous flutter versus vibration.

The methods of (14)C-2-deoxyglucose ((14)C-2DG) metabolic mapping and optical intrinsic signal (OIS) imaging were used to evaluate the response evoked in the contralateral primary somatosensory receiving areas (SI and SII) of anesthetized cats by either 25 Hz ("flutter") or 200 Hz ("vibration") sinusoidal vertical skin displacement stimulation of the central pad on the distal forepaw. Unilateral 25-Hz stimulation consistently evoked a localized region of elevated (14)C-2DG uptake in both SI and SII in the contralateral hemisphere. In contrast, 200-Hz stimulation did not evoke elevated (14)C-2DG uptake in the contralateral SI but evoked a prominent, localized region of increased (14)C-2DG uptake in the contralateral SII. Experiments in which the OIS was recorded yielded results that complemented and extended the findings obtained with the 2DG method. First, 25-Hz central-pad stimulation evoked an increase in absorbance in a region in the contralateral SI and SII that corresponded closely to the region in which a similar stimulus evoked increased (14)C-2DG uptake. Second, 200-Hz stimulation of the central pad consistently evoked a substantial increase in absorbance in the contralateral SII but very little or no increase in absorbance in the contralateral SI. And third, 200-Hz central-pad stimulation usually evoked a decrease in absorbance in the same contralateral SI region that underwent an increase in absorbance during same-site 25-Hz stimulation. Experiments in which the OIS responses of both SI and SII were recorded simultaneously demonstrated that continuous (>1 s) 25-Hz central-pad stimulation evokes a prominent increase in absorbance in both SI and SII in the contralateral hemisphere, whereas only SII undergoes a sustained prominent increase in absorbance in response to 200-Hz stimulation to the same central-pad site. SI exhibits an initial, transient increase in absorbance in response to 200-Hz stimulation and at durations of stimulation >1 s, undergoes a decrease in absorbance. It was found that the stimulus-evoked absorbance changes in the contralateral SI and SII are correlated significantly during vibrotactile stimulation of the central pad-positively with 25-Hz stimulation and negatively with 200-Hz stimulation. The findings are interpreted to indicate that 25-Hz central-pad stimulation of the central pad evokes spatially localized and vigorous neuronal activation within both SI and SII in the contralateral hemisphere and that although 200-Hz stimulation evokes vigorous and well maintained neuronal activation within the contralateral SII, the principal effect on the contralateral SI of a 200-Hz stimulus lasting >1 s is inhibitory.

Animals↗

PubMed2026

Small Copy Number Neutral Intrachromosomal Translocation of PAX6 and Aniridia.

IMPORTANCE: Approximately 5% to 10% of individuals with classic aniridia do not receive a molecular diagnosis after clinical testing for variants in PAX6 and its downstream regulatory region. OBJECTIVE: To apply optical genome mapping (OGM) and long-read whole-genome sequencing (lrWGS) to diagnose an individual with unexplained classic aniridia. DESIGN, SETTING, AND PARTICIPANTS: High-quality DNA was extracted from the blood of a 16-year-old male patient with classic aniridia and prior negative clinical test results that included sequencing and copy number analysis of PAX6 exons and downstream regulatory region as well as genomic analysis via short-read whole-genome sequencing (srWGS) and analyzed using OGM and lrWGS. All analyses were performed in a research laboratory in Wisconsin from January 2019 to September 2025. INTERVENTIONS: OGM and lrWGS. MAIN OUTCOMES AND MEASURES: Identification of a structural variant disrupting PAX6 expression in an individual with classic aniridia, following negative prior testing including srWGS. RESULTS: OGM identified a 55-kb deletion on 11p13 encompassing all PAX6 exons and exon 12 of ELP4, with insertion of this segment into 11q21. lrWGS delineated the exact breakpoints, confirming that the downstream regulatory region, required for normal PAX6 expression, remained at the 11p13 locus. Consequently, the translocated copy of PAX6 at 11q21 is expected to lack expression due to the loss of its essential regulatory elements. CONCLUSIONS AND RELEVANCE: These findings in an individual with classic aniridia harboring an intrachromosomal rearrangement at the PAX6 locus identified by OGM and lrWGS may represent the smallest reported structural variant to separate the PAX6 coding sequence from its downstream regulatory region. This structural variant may have fallen below the detection threshold of srWGS due to its balanced nature and small size, suggesting OGM and lrWGS would be needed for definitive identification.

Aniridia↗

PubMed2024

Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci.

The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a complex genomic rearrangement (CGR). Although it has been identified as an important pathogenic DNA mutation signature in genomic disorders and cancer genomes, its architecture remains unresolved. Here, we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the DNA of 24 patients identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted structural variant (SV) haplotypes. Using a combination of short-read genome sequencing (GS), long-read GS, optical genome mapping, and single-cell DNA template strand sequencing (strand-seq), the haplotype structure was resolved in 18 samples. The point of template switching in 4 samples was shown to be a segment of ∼2.2-5.5 kb of 100% nucleotide similarity within inverted repeat pairs. These data provide experimental evidence that inverted low-copy repeats act as recombinant substrates. This type of CGR can result in multiple conformers generating diverse SV haplotypes in susceptible dosage-sensitive loci.

Humans↗

PubMed2003

Intravitreal triamcinolone for refractory pseudophakic macular edema.

PURPOSE: To evaluate the efficacy of intravitreal triamcinolone in refractory pseudophakic cystoid macular edema. DESIGN: A prospective, interventional case series. METHODS: Three eyes of three patients with longstanding pseudophakic cystoid macular edema following uncomplicated cataract surgery, refractory to any medication, were treated with 8 mg of intravitreal triamcinolone. All three eyes were evaluated before injection and throughout follow-up with the Early Treatment Diabetic Retinopathy Study's visual acuity chart, fluorescein angiography, and macular mapping using optical coherence tomography. RESULTS: A month after intravitreal triamcinolone injection, a dramatic decrease in macular thickness was noted by optical coherence tomography in all three eyes (from a mean of 502-233 microm). Mean improvement in visual acuity was 3.7 Snellen lines. Two to 4 months after triamcinolone injection, however, the edema recurred in all cases, to the same degree as before the injection, combined with a decrease in vision. Two eyes underwent a second injection of triamcinolone, and macular thickness decreased, but the edema again recurred 3 months after injection. CONCLUSION: Intravitreal injection of triamcinolone induces striking regression, within 1 month, of chronic refractory macular edema. This regression appears to be transient, however, even after a second injection.

Aged↗