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Jan Kremers - One of the best experts on this subject based on the ideXlab platform.
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a modified Silent Substitution electroretinography protocol to separate photoreceptor subclass function in lightly sedated dogs
Veterinary Ophthalmology, 2021Co-Authors: E. N. Wise, Jan Kremers, Freya M. Mowat, Melanie L. FosterAbstract:OBJECTIVE A previously published study successfully isolated photoreceptor responses from canine rods, long/medium-wavelength (L/M) cones, and short-wavelength (S) cones using Silent Substitution electroretinography (ERG) performed under general anesthesia. We hypothesized that responses would be similar in dogs under sedation and that a curtailed protocol suitable for use in clinical patients could effectively isolate responses from all three photoreceptor subtypes. ANIMALS STUDIED Three normal adult purpose-bred beagles (2 females and 1 male). METHODS Dogs were dark-adapted for 1 hour. Sine wave color stimuli were delivered using LEDs in a Ganzfeld dome. The ERG protocol under anesthesia was performed as previously published; sedated ERG protocols were performed after a 3-day washout period. Intravenous sedation (dexmedetomidine 1.25 mcg/kg, butorphanol 0.1 mg/kg) was administered for sedation. Statistical analysis was performed using two-way repeated-measures ANOVA and linear regression. RESULTS In both anesthetized and sedated animals, rod-derived responses peaked at low frequency (4-12 Hz), L/M-cone responses peaked at high frequency (32-38 Hz), and S-cone responses peaked at low frequency (4-12 Hz). The frequencies eliciting maximal responses were similar in sedated and anesthetized protocols, although rod amplitudes were significantly higher in the sedated protocols compared with anesthetized (P < .001). CONCLUSION We present a clinically applicable method to consistently isolate rod and cone subclass function in sedated dogs. This may allow detailed evaluation of photoreceptor function in clinical patients with rod or cone subclass deficits without the need for general anesthesia or protracted adaptation times.
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Photoreceptor-Specific Loss of Perifoveal Temporal Contrast Sensitivity in Retinitis Pigmentosa.
Translational vision science & technology, 2020Co-Authors: Cord Huchzermeyer, Julien Fars, Jan KremersAbstract:Purpose Inherited retinal diseases affect the L-, M-, S-cones and rods in distinct ways, which calls for new methods that enable quantification of photoreceptor-specific functions. We tested the feasibility of using the Silent Substitution paradigm to estimate photoreceptor-driven temporal contrast sensitivity (tCS) functions in patients with retinitis pigmentosa. Methods The Silent Substitution paradigm is based on Substitution of lights of different spectral composition; this offers considerable advantage over other stimulation techniques. We used a four-primary LED stimulator to create perifoveal annular stimuli (2° inner, 12° outer diameters) and used a triple Silent Substitution to probe photoreceptor-selective tCS. Measurements were performed in a heterogeneous cohort of 15 patients with retinitis pigmentosa and related to those in a control group of nine color-normal healthy observers. Age differences between groups were addressed with a model of age-related normal contrast sensitivity derived from measurements in 20 healthy observers aged between 23 and 83 years. Results The age-related loss of tCS amounted to 0.1 dB/year in healthy subjects across all photoreceptor subtypes. In patients, tCS was decreased for every photoreceptor subtype; however, S-cone- and rod-driven sensitivities were most strongly affected. Postreceptoral mechanisms were not affected. Conclusions This feasibility study provides evidence that the Silent Substitution technique enables the estimation of photoreceptor-selective tCS functions and can serve as an accurate biomarker of photoreceptor-specific contrast sensitivity loss in patients with retinitis pigmentosa. Translational relevance We aim to develop tests of visual function for clinical trials of novel therapies for inherited retinal diseases from methods that can currently be used only in vision research labs.
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in vivo electroretinographic differentiation of rod short wavelength and long medium wavelength cone responses in dogs using Silent Substitution stimuli
Experimental Eye Research, 2019Co-Authors: Freya M. Mowat, Elisabeth Wise, Melanie L. Foster, Jan KremersAbstract:Abstract The canine species has dichromatic color vision comprising short-wavelength (S-) and long/medium (L/M-) wavelength-sensitive cones with peak spectral sensitivity of 429–435 nm and 555 nm respectively. Although differentiation of rod- and cone-mediated responses by electroretinogram (ERG) in dogs is commonly performed, and standards have been developed based on standards for human observers, methods to differentiate S- and L/M-cone responses in dogs have not been described. We developed flicker protocols derived from previously published rod and cone spectral sensitivities. We used a double Silent Substitution paradigm to isolate responses from each of the 3 photoreceptor subclasses. ERG responses were measured to sine-wave modulation of photoreceptor excitation at different temporal frequencies (between 4 and 56 Hz) and mean luminance (between 3.25 and 130 cd/m2) on 6 different normal dogs (3 adult female, and 3 adult male beagles) and one female beagle dog with suspected hereditary congenital stationary night blindness (CSNB). Peak rod driven response amplitudes were achieved with low frequency (4 Hz, maximal range 4–12 Hz) and low mean luminance (3.25 cd/m2). In contrast, peak L/M-cone driven response amplitudes were achieved with high frequency (32 Hz, maximal range 28–44 Hz) and high mean luminance (32.5–130 cd/m2). Maximal S-cone driven responses were obtained with low frequency stimuli (4 Hz, maximal range 4–12 Hz) and 32.5–130 cd/m2 mean luminance. The dog with CSNB had reduced rod- and S-cone-driven responses, but normal/supernormal L/M cone-driven responses. We have developed methods to differentiate rod, S- and L/M-cone function in dogs using Silent Substitution methods. The influence of temporal frequency and mean luminance on the ERGs originating in each photoreceptor type can now be studied independently. Dogs and humans have similar L/M cone responses, whereas mice have significantly different L/M responses. This work will facilitate a greater understanding of canine retinal electrophysiology and will complement the study of canine models of human hereditary photoreceptor disorders.
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In vivo electroretinographic differentiation of rod, short-wavelength and long/medium-wavelength cone responses in dogs using Silent Substitution stimuli.
Experimental eye research, 2019Co-Authors: Freya M. Mowat, Elisabeth Wise, Melanie L. Foster, Jan KremersAbstract:Abstract The canine species has dichromatic color vision comprising short-wavelength (S-) and long/medium (L/M-) wavelength-sensitive cones with peak spectral sensitivity of 429–435 nm and 555 nm respectively. Although differentiation of rod- and cone-mediated responses by electroretinogram (ERG) in dogs is commonly performed, and standards have been developed based on standards for human observers, methods to differentiate S- and L/M-cone responses in dogs have not been described. We developed flicker protocols derived from previously published rod and cone spectral sensitivities. We used a double Silent Substitution paradigm to isolate responses from each of the 3 photoreceptor subclasses. ERG responses were measured to sine-wave modulation of photoreceptor excitation at different temporal frequencies (between 4 and 56 Hz) and mean luminance (between 3.25 and 130 cd/m2) on 6 different normal dogs (3 adult female, and 3 adult male beagles) and one female beagle dog with suspected hereditary congenital stationary night blindness (CSNB). Peak rod driven response amplitudes were achieved with low frequency (4 Hz, maximal range 4–12 Hz) and low mean luminance (3.25 cd/m2). In contrast, peak L/M-cone driven response amplitudes were achieved with high frequency (32 Hz, maximal range 28–44 Hz) and high mean luminance (32.5–130 cd/m2). Maximal S-cone driven responses were obtained with low frequency stimuli (4 Hz, maximal range 4–12 Hz) and 32.5–130 cd/m2 mean luminance. The dog with CSNB had reduced rod- and S-cone-driven responses, but normal/supernormal L/M cone-driven responses. We have developed methods to differentiate rod, S- and L/M-cone function in dogs using Silent Substitution methods. The influence of temporal frequency and mean luminance on the ERGs originating in each photoreceptor type can now be studied independently. Dogs and humans have similar L/M cone responses, whereas mice have significantly different L/M responses. This work will facilitate a greater understanding of canine retinal electrophysiology and will complement the study of canine models of human hereditary photoreceptor disorders.
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Electrodiagnosis of dichromacy.
Vision research, 2019Co-Authors: Mirella Telles Salgueiro Barboni, Tina I. Tsai, Einat Hauzman, Balázs Nagy, Cristiane Maria Gomes Martins, Avinash J. Aher, Daniela Maria Oliveira Bonci, Dora Fix Ventura, Jan KremersAbstract:Abstract Retinal and cortical signals initiated by a single cone type can be recorded using the spectral compensation (or Silent Substitution) paradigm. Moreover, responses to instantaneous excitation increments combined with gradual excitation decreases are dominated by the response to the excitation increment. Similarly, the response to a sudden excitation decrement dominates the overall response when combined with a gradual excitation increase. Here ERGs and VEPs were recorded from 34 volunteers [25.9 ± 10.4 years old (mean ± 1 SD); 25 males, 9 females] to sawtooth flicker (4 Hz) stimuli that elicited L- or M-cone responses using triple Silent Substitution. The mean luminance (284 cd/m2) and the mean chromaticity (x = 0.5686, y = 0.3716; CIE 1931 color space) remained constant and thus the state of adaptation was the same in all conditions. Color discrimination thresholds along protan, deutan, and tritan axes were obtained from all participants. Dichromatic subjects were genetically characterized by molecular analysis of their opsin genes. ERG responses to L-cone stimuli were absent in protanopes whereas ERG responses to M-cone stimuli were strongly reduced in deuteranopes. Dichromats showed generally reduced VEP amplitudes. Responses to cone-specific stimuli obtained with standard electrophysiological methods may give the same classification as that obtained with the Cambridge Colour Test and in some cases with the genetic analysis of the L- and M-opsin genes. Therefore, cone-specific ERGs and VEPs may be reliable methods to detect cone dysfunction. The present data confirm and emphasize the potential use of cone-specific stimulation, combined with standard visual electrodiagnostic protocols.
Freya M. Mowat - One of the best experts on this subject based on the ideXlab platform.
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a modified Silent Substitution electroretinography protocol to separate photoreceptor subclass function in lightly sedated dogs
Veterinary Ophthalmology, 2021Co-Authors: E. N. Wise, Jan Kremers, Freya M. Mowat, Melanie L. FosterAbstract:OBJECTIVE A previously published study successfully isolated photoreceptor responses from canine rods, long/medium-wavelength (L/M) cones, and short-wavelength (S) cones using Silent Substitution electroretinography (ERG) performed under general anesthesia. We hypothesized that responses would be similar in dogs under sedation and that a curtailed protocol suitable for use in clinical patients could effectively isolate responses from all three photoreceptor subtypes. ANIMALS STUDIED Three normal adult purpose-bred beagles (2 females and 1 male). METHODS Dogs were dark-adapted for 1 hour. Sine wave color stimuli were delivered using LEDs in a Ganzfeld dome. The ERG protocol under anesthesia was performed as previously published; sedated ERG protocols were performed after a 3-day washout period. Intravenous sedation (dexmedetomidine 1.25 mcg/kg, butorphanol 0.1 mg/kg) was administered for sedation. Statistical analysis was performed using two-way repeated-measures ANOVA and linear regression. RESULTS In both anesthetized and sedated animals, rod-derived responses peaked at low frequency (4-12 Hz), L/M-cone responses peaked at high frequency (32-38 Hz), and S-cone responses peaked at low frequency (4-12 Hz). The frequencies eliciting maximal responses were similar in sedated and anesthetized protocols, although rod amplitudes were significantly higher in the sedated protocols compared with anesthetized (P < .001). CONCLUSION We present a clinically applicable method to consistently isolate rod and cone subclass function in sedated dogs. This may allow detailed evaluation of photoreceptor function in clinical patients with rod or cone subclass deficits without the need for general anesthesia or protracted adaptation times.
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A modified Silent Substitution electroretinography protocol to separate photoreceptor subclass function in lightly sedated dogs.
Veterinary ophthalmology, 2020Co-Authors: E. N. Wise, Melanie L. Foster, J. Kremers, Freya M. MowatAbstract:OBJECTIVE A previously published study successfully isolated photoreceptor responses from canine rods, long/medium-wavelength (L/M) cones, and short-wavelength (S) cones using Silent Substitution electroretinography (ERG) performed under general anesthesia. We hypothesized that responses would be similar in dogs under sedation and that a curtailed protocol suitable for use in clinical patients could effectively isolate responses from all three photoreceptor subtypes. ANIMALS STUDIED Three normal adult purpose-bred beagles (2 females and 1 male). METHODS Dogs were dark-adapted for 1 hour. Sine wave color stimuli were delivered using LEDs in a Ganzfeld dome. The ERG protocol under anesthesia was performed as previously published; sedated ERG protocols were performed after a 3-day washout period. Intravenous sedation (dexmedetomidine 1.25 mcg/kg, butorphanol 0.1 mg/kg) was administered for sedation. Statistical analysis was performed using two-way repeated-measures ANOVA and linear regression. RESULTS In both anesthetized and sedated animals, rod-derived responses peaked at low frequency (4-12 Hz), L/M-cone responses peaked at high frequency (32-38 Hz), and S-cone responses peaked at low frequency (4-12 Hz). The frequencies eliciting maximal responses were similar in sedated and anesthetized protocols, although rod amplitudes were significantly higher in the sedated protocols compared with anesthetized (P
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in vivo electroretinographic differentiation of rod short wavelength and long medium wavelength cone responses in dogs using Silent Substitution stimuli
Experimental Eye Research, 2019Co-Authors: Freya M. Mowat, Elisabeth Wise, Melanie L. Foster, Jan KremersAbstract:Abstract The canine species has dichromatic color vision comprising short-wavelength (S-) and long/medium (L/M-) wavelength-sensitive cones with peak spectral sensitivity of 429–435 nm and 555 nm respectively. Although differentiation of rod- and cone-mediated responses by electroretinogram (ERG) in dogs is commonly performed, and standards have been developed based on standards for human observers, methods to differentiate S- and L/M-cone responses in dogs have not been described. We developed flicker protocols derived from previously published rod and cone spectral sensitivities. We used a double Silent Substitution paradigm to isolate responses from each of the 3 photoreceptor subclasses. ERG responses were measured to sine-wave modulation of photoreceptor excitation at different temporal frequencies (between 4 and 56 Hz) and mean luminance (between 3.25 and 130 cd/m2) on 6 different normal dogs (3 adult female, and 3 adult male beagles) and one female beagle dog with suspected hereditary congenital stationary night blindness (CSNB). Peak rod driven response amplitudes were achieved with low frequency (4 Hz, maximal range 4–12 Hz) and low mean luminance (3.25 cd/m2). In contrast, peak L/M-cone driven response amplitudes were achieved with high frequency (32 Hz, maximal range 28–44 Hz) and high mean luminance (32.5–130 cd/m2). Maximal S-cone driven responses were obtained with low frequency stimuli (4 Hz, maximal range 4–12 Hz) and 32.5–130 cd/m2 mean luminance. The dog with CSNB had reduced rod- and S-cone-driven responses, but normal/supernormal L/M cone-driven responses. We have developed methods to differentiate rod, S- and L/M-cone function in dogs using Silent Substitution methods. The influence of temporal frequency and mean luminance on the ERGs originating in each photoreceptor type can now be studied independently. Dogs and humans have similar L/M cone responses, whereas mice have significantly different L/M responses. This work will facilitate a greater understanding of canine retinal electrophysiology and will complement the study of canine models of human hereditary photoreceptor disorders.
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In vivo electroretinographic differentiation of rod, short-wavelength and long/medium-wavelength cone responses in dogs using Silent Substitution stimuli.
Experimental eye research, 2019Co-Authors: Freya M. Mowat, Elisabeth Wise, Melanie L. Foster, Jan KremersAbstract:Abstract The canine species has dichromatic color vision comprising short-wavelength (S-) and long/medium (L/M-) wavelength-sensitive cones with peak spectral sensitivity of 429–435 nm and 555 nm respectively. Although differentiation of rod- and cone-mediated responses by electroretinogram (ERG) in dogs is commonly performed, and standards have been developed based on standards for human observers, methods to differentiate S- and L/M-cone responses in dogs have not been described. We developed flicker protocols derived from previously published rod and cone spectral sensitivities. We used a double Silent Substitution paradigm to isolate responses from each of the 3 photoreceptor subclasses. ERG responses were measured to sine-wave modulation of photoreceptor excitation at different temporal frequencies (between 4 and 56 Hz) and mean luminance (between 3.25 and 130 cd/m2) on 6 different normal dogs (3 adult female, and 3 adult male beagles) and one female beagle dog with suspected hereditary congenital stationary night blindness (CSNB). Peak rod driven response amplitudes were achieved with low frequency (4 Hz, maximal range 4–12 Hz) and low mean luminance (3.25 cd/m2). In contrast, peak L/M-cone driven response amplitudes were achieved with high frequency (32 Hz, maximal range 28–44 Hz) and high mean luminance (32.5–130 cd/m2). Maximal S-cone driven responses were obtained with low frequency stimuli (4 Hz, maximal range 4–12 Hz) and 32.5–130 cd/m2 mean luminance. The dog with CSNB had reduced rod- and S-cone-driven responses, but normal/supernormal L/M cone-driven responses. We have developed methods to differentiate rod, S- and L/M-cone function in dogs using Silent Substitution methods. The influence of temporal frequency and mean luminance on the ERGs originating in each photoreceptor type can now be studied independently. Dogs and humans have similar L/M cone responses, whereas mice have significantly different L/M responses. This work will facilitate a greater understanding of canine retinal electrophysiology and will complement the study of canine models of human hereditary photoreceptor disorders.
Dmitry A Filatov - One of the best experts on this subject based on the ideXlab platform.
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A Gradient of Silent Substitution Rate in the Human Pseudoautosomal Region
Molecular biology and evolution, 2003Co-Authors: Dmitry A FilatovAbstract:It has been demonstrated that recombination in the human p-arm pseudoautosomal region (p-PAR) is at least twenty times more frequent than the genomic average of approximately 1 cM/Mb, which may affect Substitution patterns and rates in this region. Here I report the analysis of Substitution patterns and rates in 10 human, chimpanzee, gorilla, and orangutan genes across the p-PAR. Between species Silent divergence in the p-PAR forms a gradient, increasing toward the telomere. The correlation of Silent divergence with distance from the p-PAR boundary is highly significant (rho = 0.911, P T and G C Substitutions are taken into account (rho = 0.82, P < 0.01). I hypothesize that the Substitution rate gradient in the p-PAR is due to the mutagenic effect of recombination, which is very frequent in the distal human p-PAR and might be lower near the p-PAR boundary.
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a gradient of Silent Substitution rate in the human pseudoautosomal region
Molecular Biology and Evolution, 2003Co-Authors: Dmitry A FilatovAbstract:It has been demonstrated that recombination in the human p-arm pseudoautosomal region (p-PAR) is at least twenty times more frequent than the genomic average of ∼1 cM/Mb, which may affect Substitution patterns and rates in this region. Here I report the analysis of Substitution patterns and rates in 10 human, chimpanzee, gorilla, and orangutan genes across the p-PAR. Between species Silent divergence in the p-PAR forms a gradient, increasing toward the telomere. The correlation of Silent divergence with distance from the p-PAR boundary is highly significant (p = 0.911, P < 0.001). After exclusion of the CpG dinucleotides this correlation is still significant (p = 0.89, P < 0.01), thus the Substitution rate gradient cannot be explained solely by the differences in the extent of methylation across the p-PAR. Frequent recombination in the PAR may result in a relatively strong effect of biased gene conversion (BGC), which, because of the increased probability of fixation of the G or C nucleotides at (A or T)/(G or C) segregating sites, may affect Substitution rates. BGC, however, does not seem to be the factor creating the Substitution rate gradient in the p-PAR, because the only gradient is still detactable if only A↔T and G↔C Substitutions are taken into account (p = 0.82, P < 0.01). I hypothesize that the Substitution rate gradient in the p-PAR is due to the mutagenic effect of recombination, which is very frequent in the distal human p-PAR and might be lower near the p-PAR boundary.
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Substitution Rates in the X- and Y-Linked Genes of the Plants, Silene latifolia and S. dioica
Molecular biology and evolution, 2002Co-Authors: Dmitry A Filatov, Deborah CharlesworthAbstract:Theory predicts that selection should be less effective in the nonrecombining genes of Y-chromosomes, relative to the situation for genes on the other chromosomes, and this should lead to the accumulation of deleterious nonsynonymous Substitutions. In addition, synonymous Substitution rates may differ between X- and Y-linked genes because of the male-driven evolution effect and also because of actual differences in per-replication mutation rates between the sex chromosomes. Here, we report the first study of synonymous and nonsynonymous Substitution rates on plant sex chromosomes. We sequenced two pairs of sex-linked genes, SlX1-SlY1 and SlX4-SlY4, from dioecious Silene latifolia and S. dioica, and their non-sex-linked homologues from nondioecious S. vulgaris and Lychnis flos-jovis, respectively. The rate of nonsynonymous Substitutions in the SlY4 gene is significantly higher than that in the SlX4 gene. Silent Substitution rates are also significantly higher in both Y-linked genes, compared with their X-linked homologues. The higher nonsynonymous Substitution rate in the SlY4 gene is therefore likely to be caused by a mutation rate difference between the sex chromosomes. The difference in Silent Substitution rates between the SlX4 and SlY4 genes is too great to be explained solely by a higher per-generation mutation rate in males than females. It is thus probably caused by a difference in per-replication mutation rates between the sex chromosomes. This suggests that the local mutation rate can change in a relatively short evolutionary time.
Melanie L. Foster - One of the best experts on this subject based on the ideXlab platform.
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a modified Silent Substitution electroretinography protocol to separate photoreceptor subclass function in lightly sedated dogs
Veterinary Ophthalmology, 2021Co-Authors: E. N. Wise, Jan Kremers, Freya M. Mowat, Melanie L. FosterAbstract:OBJECTIVE A previously published study successfully isolated photoreceptor responses from canine rods, long/medium-wavelength (L/M) cones, and short-wavelength (S) cones using Silent Substitution electroretinography (ERG) performed under general anesthesia. We hypothesized that responses would be similar in dogs under sedation and that a curtailed protocol suitable for use in clinical patients could effectively isolate responses from all three photoreceptor subtypes. ANIMALS STUDIED Three normal adult purpose-bred beagles (2 females and 1 male). METHODS Dogs were dark-adapted for 1 hour. Sine wave color stimuli were delivered using LEDs in a Ganzfeld dome. The ERG protocol under anesthesia was performed as previously published; sedated ERG protocols were performed after a 3-day washout period. Intravenous sedation (dexmedetomidine 1.25 mcg/kg, butorphanol 0.1 mg/kg) was administered for sedation. Statistical analysis was performed using two-way repeated-measures ANOVA and linear regression. RESULTS In both anesthetized and sedated animals, rod-derived responses peaked at low frequency (4-12 Hz), L/M-cone responses peaked at high frequency (32-38 Hz), and S-cone responses peaked at low frequency (4-12 Hz). The frequencies eliciting maximal responses were similar in sedated and anesthetized protocols, although rod amplitudes were significantly higher in the sedated protocols compared with anesthetized (P < .001). CONCLUSION We present a clinically applicable method to consistently isolate rod and cone subclass function in sedated dogs. This may allow detailed evaluation of photoreceptor function in clinical patients with rod or cone subclass deficits without the need for general anesthesia or protracted adaptation times.
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A modified Silent Substitution electroretinography protocol to separate photoreceptor subclass function in lightly sedated dogs.
Veterinary ophthalmology, 2020Co-Authors: E. N. Wise, Melanie L. Foster, J. Kremers, Freya M. MowatAbstract:OBJECTIVE A previously published study successfully isolated photoreceptor responses from canine rods, long/medium-wavelength (L/M) cones, and short-wavelength (S) cones using Silent Substitution electroretinography (ERG) performed under general anesthesia. We hypothesized that responses would be similar in dogs under sedation and that a curtailed protocol suitable for use in clinical patients could effectively isolate responses from all three photoreceptor subtypes. ANIMALS STUDIED Three normal adult purpose-bred beagles (2 females and 1 male). METHODS Dogs were dark-adapted for 1 hour. Sine wave color stimuli were delivered using LEDs in a Ganzfeld dome. The ERG protocol under anesthesia was performed as previously published; sedated ERG protocols were performed after a 3-day washout period. Intravenous sedation (dexmedetomidine 1.25 mcg/kg, butorphanol 0.1 mg/kg) was administered for sedation. Statistical analysis was performed using two-way repeated-measures ANOVA and linear regression. RESULTS In both anesthetized and sedated animals, rod-derived responses peaked at low frequency (4-12 Hz), L/M-cone responses peaked at high frequency (32-38 Hz), and S-cone responses peaked at low frequency (4-12 Hz). The frequencies eliciting maximal responses were similar in sedated and anesthetized protocols, although rod amplitudes were significantly higher in the sedated protocols compared with anesthetized (P
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in vivo electroretinographic differentiation of rod short wavelength and long medium wavelength cone responses in dogs using Silent Substitution stimuli
Experimental Eye Research, 2019Co-Authors: Freya M. Mowat, Elisabeth Wise, Melanie L. Foster, Jan KremersAbstract:Abstract The canine species has dichromatic color vision comprising short-wavelength (S-) and long/medium (L/M-) wavelength-sensitive cones with peak spectral sensitivity of 429–435 nm and 555 nm respectively. Although differentiation of rod- and cone-mediated responses by electroretinogram (ERG) in dogs is commonly performed, and standards have been developed based on standards for human observers, methods to differentiate S- and L/M-cone responses in dogs have not been described. We developed flicker protocols derived from previously published rod and cone spectral sensitivities. We used a double Silent Substitution paradigm to isolate responses from each of the 3 photoreceptor subclasses. ERG responses were measured to sine-wave modulation of photoreceptor excitation at different temporal frequencies (between 4 and 56 Hz) and mean luminance (between 3.25 and 130 cd/m2) on 6 different normal dogs (3 adult female, and 3 adult male beagles) and one female beagle dog with suspected hereditary congenital stationary night blindness (CSNB). Peak rod driven response amplitudes were achieved with low frequency (4 Hz, maximal range 4–12 Hz) and low mean luminance (3.25 cd/m2). In contrast, peak L/M-cone driven response amplitudes were achieved with high frequency (32 Hz, maximal range 28–44 Hz) and high mean luminance (32.5–130 cd/m2). Maximal S-cone driven responses were obtained with low frequency stimuli (4 Hz, maximal range 4–12 Hz) and 32.5–130 cd/m2 mean luminance. The dog with CSNB had reduced rod- and S-cone-driven responses, but normal/supernormal L/M cone-driven responses. We have developed methods to differentiate rod, S- and L/M-cone function in dogs using Silent Substitution methods. The influence of temporal frequency and mean luminance on the ERGs originating in each photoreceptor type can now be studied independently. Dogs and humans have similar L/M cone responses, whereas mice have significantly different L/M responses. This work will facilitate a greater understanding of canine retinal electrophysiology and will complement the study of canine models of human hereditary photoreceptor disorders.
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In vivo electroretinographic differentiation of rod, short-wavelength and long/medium-wavelength cone responses in dogs using Silent Substitution stimuli.
Experimental eye research, 2019Co-Authors: Freya M. Mowat, Elisabeth Wise, Melanie L. Foster, Jan KremersAbstract:Abstract The canine species has dichromatic color vision comprising short-wavelength (S-) and long/medium (L/M-) wavelength-sensitive cones with peak spectral sensitivity of 429–435 nm and 555 nm respectively. Although differentiation of rod- and cone-mediated responses by electroretinogram (ERG) in dogs is commonly performed, and standards have been developed based on standards for human observers, methods to differentiate S- and L/M-cone responses in dogs have not been described. We developed flicker protocols derived from previously published rod and cone spectral sensitivities. We used a double Silent Substitution paradigm to isolate responses from each of the 3 photoreceptor subclasses. ERG responses were measured to sine-wave modulation of photoreceptor excitation at different temporal frequencies (between 4 and 56 Hz) and mean luminance (between 3.25 and 130 cd/m2) on 6 different normal dogs (3 adult female, and 3 adult male beagles) and one female beagle dog with suspected hereditary congenital stationary night blindness (CSNB). Peak rod driven response amplitudes were achieved with low frequency (4 Hz, maximal range 4–12 Hz) and low mean luminance (3.25 cd/m2). In contrast, peak L/M-cone driven response amplitudes were achieved with high frequency (32 Hz, maximal range 28–44 Hz) and high mean luminance (32.5–130 cd/m2). Maximal S-cone driven responses were obtained with low frequency stimuli (4 Hz, maximal range 4–12 Hz) and 32.5–130 cd/m2 mean luminance. The dog with CSNB had reduced rod- and S-cone-driven responses, but normal/supernormal L/M cone-driven responses. We have developed methods to differentiate rod, S- and L/M-cone function in dogs using Silent Substitution methods. The influence of temporal frequency and mean luminance on the ERGs originating in each photoreceptor type can now be studied independently. Dogs and humans have similar L/M cone responses, whereas mice have significantly different L/M responses. This work will facilitate a greater understanding of canine retinal electrophysiology and will complement the study of canine models of human hereditary photoreceptor disorders.
Deborah Charlesworth - One of the best experts on this subject based on the ideXlab platform.
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Substitution Rates in the X- and Y-Linked Genes of the Plants, Silene latifolia and S. dioica
Molecular biology and evolution, 2002Co-Authors: Dmitry A Filatov, Deborah CharlesworthAbstract:Theory predicts that selection should be less effective in the nonrecombining genes of Y-chromosomes, relative to the situation for genes on the other chromosomes, and this should lead to the accumulation of deleterious nonsynonymous Substitutions. In addition, synonymous Substitution rates may differ between X- and Y-linked genes because of the male-driven evolution effect and also because of actual differences in per-replication mutation rates between the sex chromosomes. Here, we report the first study of synonymous and nonsynonymous Substitution rates on plant sex chromosomes. We sequenced two pairs of sex-linked genes, SlX1-SlY1 and SlX4-SlY4, from dioecious Silene latifolia and S. dioica, and their non-sex-linked homologues from nondioecious S. vulgaris and Lychnis flos-jovis, respectively. The rate of nonsynonymous Substitutions in the SlY4 gene is significantly higher than that in the SlX4 gene. Silent Substitution rates are also significantly higher in both Y-linked genes, compared with their X-linked homologues. The higher nonsynonymous Substitution rate in the SlY4 gene is therefore likely to be caused by a mutation rate difference between the sex chromosomes. The difference in Silent Substitution rates between the SlX4 and SlY4 genes is too great to be explained solely by a higher per-generation mutation rate in males than females. It is thus probably caused by a difference in per-replication mutation rates between the sex chromosomes. This suggests that the local mutation rate can change in a relatively short evolutionary time.
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Low Rates of Silent Substitution in Nuclear Genes of Two Distantly Related Scrophulariaceae (Antirrhinum and Verbascum)
Molecular biology and evolution, 2001Co-Authors: Cristina P. Vieira, Deborah CharlesworthAbstract:Low levels of genetic diversity and divergence at nuclear loci have previously been observed for cycloidea and fil1-like genes within and between several Antirrhinum species, and divergence at these loci is also low between species in genera at different levels of relatedness in the former family Scrophulariaceae (Digitalis and Verbascum). The low divergence values are surprising, because (based on the sequences of chloroplast loci) the Scrophulariaceae are thought to be polyphyletic, with two anciently diverged clades, and the species we compared belonged to the two different clades. Here, we extend our studies of sequence divergence to more nuclear genes: fil2, far, globosa, and ADH: Detailed studies revealed that in Antirrhinum these genes belong to gene families. Low levels of divergence between Antirrhinum and Verbascum were observed for four of the loci studied, fil2-1, fil2-2, far-L, and globosa, similar to our previous observations. We discuss hypotheses to explain these low synonymous divergence values. For Adh, no cases of very similar sequences were found, but, rather, our sequences from the three different genera (Antirrhinum, Digitalis, and Verbascum) were all very diverged. Repeated gene duplication and loss of elements in the Adh gene family is likely in these lineages, making it impossible to determine orthology of the Adh genes.