Thyroid hormone action is required for normal cone opsin expression during mouse retinal development

PURPOSE. The expression of S- and M-opsins in the murine retina is altered in different transgenic mouse models with mutations in the thyroid hormone receptor (TR)-beta gene, demonstrating an important role of thyroid hormone (TH) in retinal development. METHODS. The spatial expression of S- and M-opsin was compared in congenital hypothyroidism and in two different TR mutant mouse models. One mouse model contains a ligand-binding mutation that abolishes TH binding and results in constitutive binding to nuclear corepressors. The second model contains a mutation that blocks binding of coactivators to the AF-2 domain without affecting TH binding. RESULTS. Hypothyroid newborn mice showed an increase in S- opsin expression that was completely independent of the genotype. Concerning M-opsin expression, hypothyroidism caused a significant decrease (P < 0.01) only in wild-type animals. When TR beta 1 and -beta 2 were T3-binding defective, the pattern of opsin expression was similar to TR beta ablation, showing increased S- opsin expression in the dorsal retina and no expression of M-opsin in the entire retina. In an unexpected finding, immunostaining for both opsins was detected when both subtypes of TR beta were mutated in the helix 12 AF-2 domain. CONCLUSIONS. The results show, for the first time, that the expression of S- and M-opsin is dependent on normal thyroid hormone levels during development.

Análise não suave e aplicações em otimização

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Stationarity and regularity of infinite collections of sets. Applications to infinitely constrained optimization

This article continues the investigation of stationarity and regularity properties of infinite collections of sets in a Banach space started in Kruger and López (J. Optim. Theory Appl. 154(2), 2012), and is mainly focused on the application of the stationarity criteria to infinitely constrained optimization problems. We consider several settings of optimization problems which involve (explicitly or implicitly) infinite collections of sets and deduce for them necessary conditions characterizing stationarity in terms of dual space elements—normals and/or subdifferentials.

Subdifferentials of Performance Functions and Calculus of Coderivatives of Set-Valued Mappings

The paper contains calculus rules for coderivatives of compositions, sums and intersections of set-valued mappings. The types of coderivatives considered correspond to Dini-Hadamard and limiting Dini-Hadamard subdifferentials in Gˆateaux differentiable spaces, Fréchet and limiting Fréchet subdifferentials in Asplund spaces and approximate subdifferentials in arbitrary Banach spaces. The key element of the unified approach to obtaining various calculus rules for various types of derivatives presented in the paper are simple formulas for subdifferentials of marginal, or performance functions.

Persons with age-related maculopathy risk genotypes and clinically normal eyes have reduced mesopic vision

PURPOSE: To determine if participants with normal visual acuity, no ophthalmoscopically signs of age-related maculopathy (ARM) in both eyes and who are carriers of the CFH, LOC387715 and HRTA1 high-risk genotypes (“gene-positive”) have impaired rod- and cone-mediated mesopic visual function compared to persons who do not carry the risk genotypes (“gene-negative”).---------- METHODS: Fifty-three Caucasian study participants (mean 55.8 ± 6.1) were genotyped for CFH, LOC387715/ARMS2 and HRTA1 polymorphisms. We genotyped single nucleotide polymorphisms (SNPs) in the CFH (rs380390), LOC387715/ARMS2 (rs10490924) and HTRA1 (rs11200638) genes using Applied Biosystems optimised TaqMan assays. We determined the critical fusion frequency (CFF) mediated by cones alone (Long, Middle and Short wavelength sensitive cones; LMS) and by the combined activities of cones and rods (LMSR). The stimuli were generated using a 4-primary photostimulator that provides independent control of the photoreceptor excitation under mesopic light levels. Visual function was further assessed using standard clinical tests, flicker perimetry and microperimetry.---------- RESULTS: The mesopic CFF mediated by rods and cones (LMSR) was significantly reduced in gene-positive compared to gene-negative participants after correction for age (p=0.03). Cone-mediated CFF (LMS) was not significantly different between gene-positive and -negative participants. There were no significant associations between flicker perimetry and microperimetry and genotype.---------- CONCLUSIONS: This is the first study to relate ARM risk genotypes with mesopic visual function in clinically normal persons. These preliminary results could become of clinical importance as mesopic vision may be used to document sub-clinical retinal changes in persons with risk genotypes and to determine whether those persons progress into manifest disease.

Cone signals and activity in myopia and emmetropia

Myopia (short-sightedness) is a common ocular disorder of children and young adults. Studies primarily using animal models have shown that the retina controls eye growth and the outer retina is likely to have a key role. One theory is that the proportion of L (long-wavelength-sensitive) and M (medium-wavelength-sensitive) cones is related to myopia development; with a high L/M cone ratio predisposing individuals to myopia. However, not all dichromats (persons with red-green colour vision deficiency) with extreme L/M cone ratios have high refractive errors. We predict that the L/M cone ratio will vary in individuals with normal trichromatic colour vision but not show a systematic difference simply due to refractive error. The aim of this study was to determine if L/M cone ratios in the central 30° are different between myopic and emmetropic young, colour normal adults. Information about L/M cone ratios was determined using the multifocal visual evoked potential (mfVEP). The mfVEP can be used to measure the response of visual cortex to different visual stimuli. The visual stimuli were generated and measurements performed using the Visual Evoked Response Imaging System (VERIS 5.1). The mfVEP was measured when the L and M cone systems were separately stimulated using the method of silent substitution. The method of silent substitution alters the output of three primary lights, each with physically different spectral distributions to control the excitation of one or more photoreceptor classes without changing the excitation of the unmodulated photoreceptor classes. The stimulus was a dartboard array subtending 30° horizontally and 30° vertically on a calibrated LCD screen. The m-sequence of the stimulus was 215-1. The N1-P1 amplitude ratio of the mfVEP was used to estimate the L/M cone ratio. Data were collected for 30 young adults (22 to 33 years of age), consisting of 10 emmetropes (+0.3±0.4 D) and 20 myopes (–3.4±1.7 D). The stimulus and analysis techniques were confirmed using responses of two dichromats. For the entire participant group, the estimated central L/M cone ratios ranged from 0.56 to 1.80 in the central 3°-13° diameter ring and from 0.94 to 1.91 in the more peripheral 13°-30° diameter ring. Within 3°-13°, the mean L/M cone ratio of the emmetropic group was 1.20±0.33 and the mean was similar, 1.20±0.26, for the myopic group. For the 13°-30° ring, the mean L/M cone ratio of the emmetropic group was 1.48±0.27 and it was slightly lower in the myopic group, 1.30±0.27. Independent-samples t-test indicated no significant difference between the L/M cone ratios of the emmetropic and myopic group for either the central 3°-13° ring (p=0.986) or the more peripheral 13°-30° ring (p=0.108). The similar distributions of estimated L/M cone ratios in the sample of emmetropes and myopes indicates that there is likely to be no association between the L/M cone ratio and refractive error in humans.

Reconstruction from incomplete data in cone-beam tomography

A method for reconstruction of an object f(x) x=(x,y,z) from a limited set of cone-beam projection data has been developed. This method uses a modified form of convolution back-projection and projection onto convex sets (POCS) for handling the limited (or incomplete) data problem. In cone-beam tomography, one needs to have a complete geometry to completely reconstruct the original three-dimensional object. While complete geometries do exist, they are of little use in practical implementations. The most common trajectory used in practical scanners is circular, which is incomplete. It is, however, possible to recover some of the information of the original signal f(x) based on a priori knowledge of the nature of f(x). If this knowledge can be posed in a convex set framework, then POCS can be utilized. In this report, we utilize this a priori knowledge as convex set constraints to reconstruct f(x) using POCS. While we demonstrate the effectiveness of our algorithm for circular trajectories, it is essentially geometry independent and will be useful in any limited-view cone-beam reconstruction.

Direct Numerical Simulation Of Hypersonic Boundary-Layer Transition Over A Blunt Cone

Direct numerical simulation of transition How over a blunt cone with a freestream Mach number of 6, Reynolds number of 10,000 based on the nose radius, and a 1-deg angle of attack is performed by using a seventh-order weighted essentially nonoscillatory scheme for the convection terms of the Navier-Stokes equations, together with an eighth-order central finite difference scheme for the viscous terms. The wall blow-and-suction perturbations, including random perturbation and multifrequency perturbation, are used to trigger the transition. The maximum amplitude of the wall-normal velocity disturbance is set to 1% of the freestream velocity. The obtained transition locations on the cone surface agree well with each other far both cases. Transition onset is located at about 500 times the nose radius in the leeward section and 750 times the nose radius in the windward section. The frequency spectrum of velocity and pressure fluctuations at different streamwise locations are analyzed and compared with the linear stability theory. The second-mode disturbance wave is deemed to be the dominating disturbance because the growth rate of the second mode is much higher than the first mode. The reason why transition in the leeward section occurs earlier than that in the windward section is analyzed. It is not because of higher local growth rate of disturbance waves in the leeward section, but because the growth start location of the dominating second-mode wave in the leeward section is much earlier than that in the windward section.

Retinal ultrastructural findings in cone degeneration

We studied an eye from a 73-year-old man with a sporadic type of retinal cone degeneration and choroidal melanoma. Histologic and ultrastructural studies of the nasal retina unaffected by the choroidal melanoma showed alterations at the outer retina predominantly involving the photoreceptors and retinal pigment epithelium. A wide spectrum of pathologic changes were observed, ranging from near normal retina showing only photoreceptor outer segment disease (distortion and kinking) to grossly pathologic regions where photoreceptor cell bodies were sparse and their outer segments absent. The retinal pigment epithelium in minimally affected regions of the retina showed an increased proportion of the melanin complement of the cell within complex granules. In severe disease, many cells showed only giant complex granules with no free melanin. Retinal pigment epithelial cell migration and relocation around blood vessels was also noted in severe disease.

Autofluorescence Findings Of A Novel Maculopathy In Patient With Spinocerebellar Ataxia Type 1 And Of A Cone - Rod Type Retinal Dysfunction In Three Generation Family With Spinocerebellar Ataxia Type 7

Purpose: To report a novel maculopathy in a patient with SCA1. To describe autofluorescence findings in family with SCA7 and associated cone-rod retinal dysfunction.Methods: 4 affected patients from two families were assessed to investigate a progressive loss of visual acuity (VA). Examinations included fundus photography, autofluorescence (AF) fundus fluorescein angiogragraphy (FFA) and optical coherence tomography. Electroretinogram (full-field) was performed in 2 affected patients. All patients had color vision testing using Ishihara pseudoisochromatic plates. Molecular analysis was performed in family 2.Results: The patient with known diagnosis of SCA1 had a visual acuity of 20/200 bilaterally and dyschromatopsia. He had saccadic pursuit. Fundus examination showed mild retinal pigment epithelium (RPE) changes at the macula. OCT showed bilateral macular serous detachment, which was not obvious at the FFA and explained his VA. AF imaging showed a central hyperfluorescence. The 45 year old proband from family 2 had a visual acuity of 200/20 and dyschromatopsia. ERG testing showed cone type dysfunction of photoreceptors. Her daughter affected at a younger age had the same ERGs findings. Fundus examination showed mild RPE changes in proband, normal findings in her daughter. AF imaging of both patients showed a ring of high density AF around the fovea. The ring was also obvious on near infrared AF. Later onset of gait imbalance led to the diagnosis of SCA7Conclusions: Within the group of spinocerebellar ataxias, only the type 7 is associated with retinal dysfunction. We present the first report of maculopathy associated with SCA1 causing severe vision loss. The ring of high density AF in SCA7 confirmed an early retinal photoreceptor dysfunction in patient with normal fundus.

Perpendicular exchange bias in IrMn/Pt/[Co/Pt](3) multilayers with cone magnetization

The perpendicular exchange bias and magnetic anisotropy were investigated in IrMn/Pt/[Co/Pt](3) multilayers through the analysis of in-plane and out-of-plane magnetization hysteresis loops. A phenomenological model was used to simulate the in-plane curves and the effective perpendicular anisotropies were obtained employing the area method. The canted state anisotropy was introduced by taking into account the first and second uniaxial anisotropy terms of the ferromagnet with the corresponding uniaxial anisotropy direction allowed to make a nonzero angle with the film`s normal. This angle, obtained from the fittings, was of approximately 15 degrees for IrMn/[Co/Pt](3) film and decreases with the introduction of Pt in the IrMn/Pt/[Co/Pt](3) system, indicating that the Pt interlayer leads to a predominant perpendicular anisotropy. A maximum of the out-of-plane anisotropy was found between 0.5 and 0.6 nm of Pt, whereas a maximum of the perpendicular exchange bias was found at 0.3 nm. These results are very similar to those obtained for IrMn/Cu/[Co/Pt](3) system; however, the decrease of the exchange bias with the spacer thickness is more abrupt and the enhacement of the perpendicular anisotropy is higher for the case of Cu spacer as compared with that of Pt spacer. The existence of a maximum in the perpendicular exchange bias as a function of the Pt layer thickness was attributed to the predominance of the enhancement of exchange bias due to more perpendicular Co moment orientation over the exponential decrease of the ferromagnetic/antiferromagnetic exchange coupling and, consequently, of the exchange-bias field. (C) 2011 Elsevier B.V. All rights reserved.

Cone contrast influence on components of the pattern onset/offset VECP

Transient visual evoked cortical potentials (VECP) were recorded from the scalp of healthy normal trichromats (n = 12). VECPs were elicited by onset/offset presentation of patterned stimuli of two kinds: isochromatic luminance-modulated, and equiluminant red-green modulated, sine wave gratings. The amplitude and latency of the major onset components of the onset/offset VECP were measured and plotted as a function of the logarithm of pooled cone contrast. The early onset components, achromatic C1 and chromatic N1, increase linearly with log contrast, but N1 has a higher contrast gain than C1. The late onset components, achromatic C2 and chromatic N2, have similar contrast gain, and similar response as a function of contrast level: both increase in the low-to-medium range of contrasts and saturate at high contrast levels. In the range of pooled cone contrast tested, C1 and N1 show similar latencies, whilst C2 shows shorter latencies than N2. We suggest that C1 and N1 are generated by the same visual mechanism with high red-green contrast gain and low luminance contrast gain, whilst C2 and N2 are generated by different visual mechanisms.

Absence of ocular interaction in flicker ERG responses reflecting cone opponent and luminance signals

The aim of the study was to investigate whether there is an ocular interaction in the flicker ERG responses reflecting luminance and cone opponency in normal human subjects. Flicker ERGs were recorded from one dilated eye of 10 healthy volunteers. Each subject was tested twice: once with and once without occluding the opposite eye. Red and green LEDs were modulated in counterphase in a Ganzfeld stimulator. ERG responses were recorded for different ratios of the modulation in the red and green LEDs and at 12 and 36 Hz. The amplitudes and phases of the fundamental components were compared between the conditions with and without occlusion. The 12-Hz flicker ERGs reflected activity of the cone opponent channel, whereas the 36-Hz data reflected luminance activity. There were no significant differences between the conditions with and without occluding the opposite eye for any of the stimulus protocols. Ocular interaction is absent in flicker ERGs reflecting cone opponent and luminance activity.

Alveolar Bone Morphology in Patients With Bilateral Complete Cleft Lip and Palate in the Mixed Dentition: Cone Beam Computed Tomography Evaluation

Objectives: To verify the thickness and level of alveolar bone around the teeth adjacent to the cleft by means of cone beam computed tomography (CBCT) in patients with complete bilateral cleft lip and palate prior to bone graft surgery and orthodontic intervention. Method: The sample comprised 10 patients with complete bilateral cleft lip and palate (five boys and five girls) in the mixed dentition. The mean age was 9.5 years, and all subjects showed a G3 interarch relationship according to the Bauru index. The thickness of alveolar bone surrounding the maxillary incisors and the maxillary canines was measured in CBCT axial section using the software iCAT Xoran System. The distance between the alveolar bone crest and the cement-enamel junction (CEJ) was measured in cross sections. Results: The tomography images showed a thin alveolar bone plate around teeth adjacent to clefts. No bone dehiscence was observed in teeth adjacent to clefts during the mixed dentition. A slight increase in the distance between the alveolar bone crest and the CEJ was observed in the mesial and lingual aspects of canines adjacent to cleft. Conclusion: In patients with BCLP in the mixed dentition, teeth adjacent to the alveolar cleft are covered by a thin alveolar bone plate. However, the level of alveolar bone crest around these teeth seems to be normal, and no bone dehiscence was identified at this age.

Quantitative analysis of OCT characteristics in patients with achromatopsia and blue-cone monochromatism

PURPOSE: To quantify optical coherence tomography (OCT) images of the central retina in patients with blue-cone monochromatism (BCM) and achromatopsia (ACH) compared with healthy control individuals. METHODS: The study included 15 patients with ACH, 6 with BCM, and 20 control subjects. Diagnosis of BCM and ACH was established by visual acuity testing, morphologic examination, color vision testing, and Ganzfeld ERG recording. OCT images were acquired with the Stratus OCT 3 (Carl Zeiss Meditec AG, Oberkochen, Germany). Foveal OCT images were analyzed by calculating longitudinal reflectivity profiles (LRPs) from scan lines. Profiles were analyzed quantitatively to determine foveal thickness and distances between reflectivity layers. RESULTS: Patients with ACH and BCM had a mean visual acuity of 20/200 and 20/60, respectively. Color vision testing results were characteristic of the diseases. The LRPs of control subjects yielded four peaks (P1-P4), presumably representing the RPE (P1), the ovoid region of the photoreceptors (P2), the external limiting membrane (ELM) (P3), and the internal limiting membrane (P4). In patients with ACH, P2 was absent, but foveal thickness (P1-P4) did not differ significantly from that in the control subjects (187 +/- 20 vs. 192 +/- 14 microm, respectively). The distance from P1 to P3 did not differ significantly (78 +/- 10 vs. 82 +/- 5 microm) between ACH and controls subjects. In patients with BCM, P3 was lacking, and P2 advanced toward P1 compared with the control subjects (32 +/- 6 vs. 48 +/- 4 microm). Foveal thickness (153 +/- 16 microm) was significantly reduced compared with that in control subjects and patients with ACH. CONCLUSIONS: Quantitative OCT image analysis reveals distinct patterns for controls subjects and patients with ACH and BCM, respectively. Quantitative analysis of OCT imaging can be useful in differentiating retinal diseases affecting photoreceptors. Foveal thickness is similar in both normal subjects and patients with ACH but is decreased in patients with BCM.