Abnormalities of the retinal cone system in retinitis pigmentosa

AbstractPatients with retinitis pigmentosa (RP) show delayed inner retinal responses as measured by the cone ERG response to a 30 Hz stimulus. To determine the extent to which this delay results from abnormalities of cone phototransduction, cone ERGs to single flashes were obtained from 21 patients with RP and a model of cone phototransduction was fitted to the leading edge of the a-waves of these ERGs. Nearly all patients showed an abnormally low sensitivity of cone phototransduction consistent with a reduction in the amplification of transduction. This abnormality can account for part of the delayed 30 Hz response. Analysis of post-receptoral potentials indicated that RP also slows the responses of the inner retina. A combination of these two factors, a sensitivity change at the receptor and a delay in the response of the inner retina, produces the delayed response of the cone flicker ERG in patients with RP

Aerodynamic Interference on Finned Slender Body

Aerodynamic interference can occur between high-speed slender bodies when in close proximity. A complex flowfield develops where shock and expansion waves from a generator body impinge upon the adjacent receiver body and modify its aerodynamic characteristics in comparison to the isolated case. The aim of this research is to quantify and understand the multibody interference effects that arise between a finned slender body and a second disturbance generator body. A parametric wind tunnel study was performed in which the effects of the receiver incidence and axial stagger were considered. Computational fluid dynamic simulations showed good agreement with the measurements, and these were used in the interpretation of the experimental results. The overall interference loads for a given multibody configuration were found to be a complex function of the pressure footprints from the compression and expansion waves emanating from the generator body as well as the flow pitch induced by the generator shockwave. These induced interference loads change sign as the shock impingement location moves aft over the receiver and in some cases cause the receiver body to become statically unstable. Overall, the observed interference effects can modify the subsequent body trajectories and may increase the likelihood of a collision

The 15 years of comet photometry: A comparative analysis of 80 comets

In 1976, a program of narrowband photometry of comets was initiated that has encompassed well over 400 nights of observations. To date, the program has provided detailed information on 80 comets, 11 of which were observed during multiple apparitions. The filters (initially isolating CN, C2, and continuum and later including C3, OH, and NH) as well as the detectors used for the observations were changed over time, and the parameters adopted in the reduction and modeling of the data have likewise evolved. Accordingly, we have re-reduced the entire database and have derived production rates using current values for scalelengths and fluorescence efficiencies. Having completed this task, the results for different comets can now be meaningfully compared. The general characteristics that are discussed include ranges in composition (molecular production rate ratios) and dustiness (gas production compared with Af(rho)). Additionally an analysis of trends on how the production rates vary with heliocentric distance and on pre- and post-perihelion asymmetries in the production rates of individual comets. Possible taxonomic groupings are also described

15 years of comet photometry: A comparative analysis of 80 comets

In 1976 we began a program of narrowband photometry of comets that has encompassed well over 400 nights of observations. To date, the program has provided detailed information on 80 comets, 11 of which have been observed on multiple apparitions. In this paper we present the observed range of compositions (molecular production rate ratios) and dustiness (gas production compared with AF-rho) for a well sampled group of comets. Based on these results we present preliminary analysis of taxonomic groupings as well as the abundance ratios we associate with a 'typical' comet

Reliability of Semiautomated Kinetic Perimetry (SKP) and Goldmann Kinetic Perimetry in Children and Adults With Retinal Dystrophies.

PurposeTo investigate the precision of visual fields (VFs) from semiautomated kinetic perimetry (SKP) on Octopus 900 perimeters, for children and adults with inherited retinal degenerations (IRDs). Goldmann manual kinetic perimetry has long been used in the diagnosis and follow-up of these patients, but SKP is becoming increasingly common. Octopus VFs (OVFs) and Goldmann VFs (GVFs) were both mapped on two occasions.MethodsNineteen females and 10 males with IRDs were tested on OVFs and GVFs, with two targets per test (V4e and one smaller target). Tests were performed in the same (randomized) order at two visits about 1 week apart. The VFs were digitized to derive isopter solid angles. Comparisons, within and between visits, were performed with paired t-tests and Bland-Altman plots.ResultsMedian age was 20 years (range, 7-70; 10 participants aged ≤17 years old). There were no significant differences in solid angles between OVFs and GVFs (P ≥ 0.06) or between the two visits' solid angles on either perimeter (P ≥ 0.30). Between-visit test-retest variability for GVFs and OVFs was similar (P ≥ 0.73), with median values of approximately 9% to 13%. Overall variability was lower for children than adults (medians of 7.5% and 12.8%, respectively).ConclusionsOctopus SKP and Goldmann perimetry produced VFs of similar size and variability.Translational relevanceOur study indicates that SKP provides a viable alternative to traditional Goldmann perimetry in clinical trials or care involving both children and adults with IRDs

Autosomal Dominant Retinal Dystrophies Caused by a Founder Splice Site Mutation, c.828+3A>T, in PRPH2 and Protein Haplotypes in trans as Modifiers.

PurposeWe determined the phenotypic variation, disease progression, and potential modifiers of autosomal dominant retinal dystrophies caused by a splice site founder mutation, c.828+3A>T, in the PRPH2 gene.MethodsA total of 62 individuals (19 families) harboring the PRPH2 c.828+3A>T mutation, had phenotype analysis by fundus appearance, electrophysiology, and visual fields. The PRPH2 haplotypes in trans were sequenced for potential modifying variants and generalized estimating equations (GEE) used for statistical analysis.ResultsSeveral distinct phenotypes caused by the PRPH2 c.828+3A>T mutation were observed and fell into two clinical categories: Group I (N = 44) with mild pattern dystrophies (PD) and Group II (N = 18) with more severe cone-rod dystrophy (CRD), retinitis pigmentosa (RP), and central areolar chorioretinal dystrophy (CACD). The PRPH2 Gln304-Lys310-Asp338 protein haplotype in trans was found in Group I only (29.6% vs. 0%), whereas the Glu304-Lys310-Gly338 haplotype was predominant in Group II (94.4% vs. 70.4%). Generalized estimating equations analysis for PD versus the CRD/CACD/RP phenotypes in individuals over 43 years alone with the PRPH2 haplotypes in trans and age as predictors, adjusted for correlation within families, confirmed a significant effect of haplotype on severity (P = 0.03) with an estimated odds ratio of 7.16 (95% confidence interval [CI] = [2.8, 18.4]).ConclusionsThe PRPH2 c.828+3A>T mutation results in multiple distinct phenotypes likely modified by protein haplotypes in trans; the odds of having the CACD/RP-like phenotype (versus the PD phenotype) are 7.16 times greater with a Glu304-Lys310-Gly338 haplotype in trans. Further functional studies of the modifying haplotypes in trans and PRPH2 splice variants may offer therapeutic targets

The very large G-protein coupled receptor VLGR1: a component of the ankle link complex required for the normal development of auditory hair bundles

Sensory hair bundles in the inner ear are composed of stereocilia that can be interconnected by a variety of different link types, including tip links, horizontal top connectors, shaft connectors, and ankle links. The ankle link antigen is an epitope specifically associated with ankle links and the calycal processes of photoreceptors in chicks. Mass spectrometry and immunoblotting were used to identify this antigen as the avian ortholog of the very large G-protein-coupled receptor VLGR1, the product of the Usher syndrome USH2C (Mass1) locus. Like ankle links, Vlgr1 is expressed transiently around the base of developing hair bundles in mice. Ankle links fail to form in the cochleae of mice carrying a targeted mutation in Vlgr1 (Vlgr1/del7TM), and the bundles become disorganized just after birth. FM1-43 [N-(3-triethylammonium)propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] dye loading and whole-cell recordings indicate mechanotransduction is impaired in cochlear, but not vestibular, hair cells of early postnatal Vlgr1/del7TM mutant mice. Auditory brainstem recordings and distortion product measurements indicate that these mice are severely deaf by the third week of life. Hair cells from the basal half of the cochlea are lost in 2-month-old Vlgr1/del7TM mice, and retinal function is mildly abnormal in aged mutants. Our results indicate that Vlgr1 is required for formation of the ankle link complex and the normal development of cochlear hair bundles

R375-87, and Pediatric Subunit United States Public Health Service (Bethesda, Maryland) grant MO1-RR0063

Full-field electroretinograms (ERGs) were obtained from very-low-birth-weight (VLBW) neonates to determine whether omega-3 (a>-3) fatty acids are essential for normal human retinal development. Eighty-one infants born at 30.4 (standard deviation, ±1.5) wk gestation were, within 10 d of birth, either enrolled to receive mother's milk (naturally containing both o>-6 and a>-3 essential fatty acids) or randomized to receive one of the infant formulas. Corn oil-based Formula A contained mainly linoleic acid (18:2 co-6) and was low in all co-3 fatty acids. Soy oil-based Formula B contained ample a-linolenic acid (18:3 a>-3) but no long-chain a>-3. Formula C, supplemented with both a-linolenic acid and marine oils, was comparable to human milk in long-chain co-3. Full-field ERGs were obtained in the special care nursery from infants aged 36 and 57 wk postconception. Ten healthy preterm infants born at 35 wk gestation were tested at 36 wk postconception. Significant differences were found among groups in rod ERG function. Post hoc comparisons showed that infants fed Formula A had significantly higher rod thresholds than infants receiving long-chain co-3 (human milk, Formula C, and intrauterine). Infants receiving Formula B had intermediate thresholds that were significantly higher than those of infants receiving intrauterine nutrition. Analysis of the leading edge of the a-wave showed that b-wave differences originated at the photoreceptor level. Differences were not present in infants at 57 wk postconception. No significant differences among groups were found in cone b-waves at 36 or 57 wk postconception. Oscillatory potentials had significantly longer implicit times at 57 wk postconception in infants fed Formula A than in infants receiving human milk. These findings suggest that retinal function varies with the dietary supply of co-3 fatty acids in VLBW infants. Invest Ophthalmol Vis Sci 33: [2365][2366][2367][2368][2369][2370][2371][2372][2373][2374][2375][2376]1992 Linoleic acid (18:2 00-6) and a-linolenic acid (18:3 a>-3) are considered essential fatty acids (EFAs) for humans because of our inability to synthesize them and the resulting deficiency syndromes when they are removed from the diet

R375-87, and Pediatric Subunit United States Public Health Service (Bethesda, Maryland) grant MO1-RR0063

Full-field electroretinograms (ERGs) were obtained from very-low-birth-weight (VLBW) neonates to determine whether omega-3 (a>-3) fatty acids are essential for normal human retinal development. Eighty-one infants born at 30.4 (standard deviation, ±1.5) wk gestation were, within 10 d of birth, either enrolled to receive mother's milk (naturally containing both o>-6 and a>-3 essential fatty acids) or randomized to receive one of the infant formulas. Corn oil-based Formula A contained mainly linoleic acid (18:2 co-6) and was low in all co-3 fatty acids. Soy oil-based Formula B contained ample a-linolenic acid (18:3 a>-3) but no long-chain a>-3. Formula C, supplemented with both a-linolenic acid and marine oils, was comparable to human milk in long-chain co-3. Full-field ERGs were obtained in the special care nursery from infants aged 36 and 57 wk postconception. Ten healthy preterm infants born at 35 wk gestation were tested at 36 wk postconception. Significant differences were found among groups in rod ERG function. Post hoc comparisons showed that infants fed Formula A had significantly higher rod thresholds than infants receiving long-chain co-3 (human milk, Formula C, and intrauterine). Infants receiving Formula B had intermediate thresholds that were significantly higher than those of infants receiving intrauterine nutrition. Analysis of the leading edge of the a-wave showed that b-wave differences originated at the photoreceptor level. Differences were not present in infants at 57 wk postconception. No significant differences among groups were found in cone b-waves at 36 or 57 wk postconception. Oscillatory potentials had significantly longer implicit times at 57 wk postconception in infants fed Formula A than in infants receiving human milk. These findings suggest that retinal function varies with the dietary supply of co-3 fatty acids in VLBW infants. Invest Ophthalmol Vis Sci 33: [2365][2366][2367][2368][2369][2370][2371][2372][2373][2374][2375][2376]1992 Linoleic acid (18:2 00-6) and a-linolenic acid (18:3 a>-3) are considered essential fatty acids (EFAs) for humans because of our inability to synthesize them and the resulting deficiency syndromes when they are removed from the diet