Rapid synaptic vesicle endocytosis in cone photoreceptors of salamander retina

PubMed Central

Van Hook, Matthew J.; Thoreson, Wallace B.

2013-01-01

Following synaptic vesicle exocytosis, neurons retrieve the fused membrane by a process of endocytosis in order to provide a supply of vesicles for subsequent release and maintain the presynaptic active zone. Rod and cone photoreceptors use a specialized structure called the synaptic ribbon that enables them to sustain high rates of neurotransmitter release. They must also employ mechanisms of synaptic vesicle endocytosis capable of keeping up with release. While much is known about endocytosis at another retinal ribbon synapse, that of the goldfish Mb1 bipolar cell, less is known about endocytosis in photoreceptors. We used capacitance recording techniques to measure vesicle membrane fusion and retrieval in photoreceptors from salamander retinal slices. We found that application of brief depolarizing steps (<100 ms) to cones evoked exocytosis followed by rapid endocytosis with a time constant ~250 ms. In some cases, the capacitance trace overshot the baseline, indicating excess endocytosis. Calcium had no effect on the time constant, but enhanced excess endocytosis resulting in a faster rate of membrane retrieval. Surprisingly, endocytosis was unaffected by blockers of dynamin, suggesting that cone endocytosis is dynamin-independent. This contrasts with synaptic vesicle endocytosis in rods, which was inhibited by the dynamin inhibitor dynasore and GTPγS introduced through the patch pipette, suggesting that the two photoreceptor types employ distinct pathways for vesicle retrieval. The fast kinetics of synaptic vesicle endocytosis in photoreceptors likely enables these cells to maintain a high rate of transmitter release, allowing them to faithfully signal changes in illumination to second-order neurons. PMID:23238726

Assessment of Rod, Cone, and Intrinsically Photosensitive Retinal Ganglion Cell Contributions to the Canine Chromatic Pupillary Response.

PubMed

Yeh, Connie Y; Koehl, Kristin L; Harman, Christine D; Iwabe, Simone; Guzman, José M; Petersen-Jones, Simon M; Kardon, Randy H; Komáromy, András M

2017-01-01

The purpose of this study was to evaluate a chromatic pupillometry protocol for specific functional assessment of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) in dogs. Chromatic pupillometry was tested and compared in 37 dogs in different stages of primary loss of rod, cone, and combined rod/cone and optic nerve function, and in 5 wild-type (WT) dogs. Eyes were stimulated with 1-s flashes of dim (1 cd/m2) and bright (400 cd/m2) blue light (for scotopic conditions) or bright red (400 cd/m2) light with 25-cd/m2 blue background (for photopic conditions). Canine retinal melanopsin/Opn4 was cloned, and its expression was evaluated using real-time quantitative reverse transcription-PCR and immunohistochemistry. Mean ± SD percentage of pupil constriction amplitudes induced by scotopic dim blue (scDB), scotopic bright blue (scBB), and photopic bright red (phBR) lights in WT dogs were 21.3% ± 10.6%, 50.0% ± 17.5%, and 19.4% ± 7.4%, respectively. Melanopsin-mediated responses to scBB persisted for several minutes (7.7 ± 4.6 min) after stimulus offset. In dogs with inherited retinal degeneration, loss of rod function resulted in absent scDB responses, followed by decreased phBR responses with disease progression and loss of cone function. Primary loss of cone function abolished phBR responses but preserved those responses to blue light (scDB and scBB). Although melanopsin/Opn4 expression was diminished with retinal degeneration, melanopsin-expressing ipRGCs were identified for the first time in both WT and degenerated canine retinas. Pupil responses elicited by light stimuli of different colors and intensities allowed differential functional assessment of canine rods, cones, and ipRGCs. Chromatic pupillometry offers an effective tool for diagnosing retinal and optic nerve diseases.

Homeostatic Plasticity Mediated by Rod-Cone Gap Junction Coupling in Retinal Degenerative Dystrophic RCS Rats

PubMed Central

Hou, Baoke; Fu, Yan; Weng, Chuanhuang; Liu, Weiping; Zhao, Congjian; Yin, Zheng Qin

2017-01-01

Rod-cone gap junctions open at night to allow rod signals to pass to cones and activate the cone-bipolar pathway. This enhances the ability to detect large, dim objects at night. This electrical synaptic switch is governed by the circadian clock and represents a novel form of homeostatic plasticity that regulates retinal excitability according to network activity. We used tracer labeling and ERG recording in the retinae of control and retinal degenerative dystrophic RCS rats. We found that in the control animals, rod-cone gap junction coupling was regulated by the circadian clock via the modulation of the phosphorylation of the melatonin synthetic enzyme arylalkylamine N-acetyltransferase (AANAT). However, in dystrophic RCS rats, AANAT was constitutively phosphorylated, causing rod-cone gap junctions to remain open. A further b/a-wave ratio analysis revealed that dystrophic RCS rats had stronger synaptic strength between photoreceptors and bipolar cells, possibly because rod-cone gap junctions remained open. This was despite the fact that a decrease was observed in the amplitude of both a- and b-waves as a result of the progressive loss of rods during early degenerative stages. These results suggest that electric synaptic strength is increased during the day to allow cone signals to pass to the remaining rods and to be propagated to rod bipolar cells, thereby partially compensating for the weak visual input caused by the loss of rods. PMID:28473754

Dopamine D1 receptor activation contributes to light-adapted changes in retinal inhibition to rod bipolar cells.

PubMed

Flood, Michael Daniel; Moore-Dotson, Johnnie M; Eggers, Erika D

2018-05-30

Dopamine modulation of retinal signaling has been shown to be an important part of retinal adaptation to increased background light levels but the role of dopamine modulation of retinal inhibition is not clear. We previously showed that light adaptation causes a large reduction in inhibition to rod bipolar cells, potentially to match the decrease in excitation after rod saturation. In this study we determined how dopamine D1 receptors in the inner retina contribute to this modulation. We found that D1 receptor activation significantly decreased the magnitude of inhibitory light responses from rod bipolar cells, while D1 receptor blockade during light adaptation partially prevented this decline. To determine what mechanisms were involved in the modulation of inhibitory light responses, we measured the effect of D1 receptor activation on spontaneous currents and currents evoked from electrically stimulating amacrine cell inputs to rod bipolar cells. D1 receptor activation decreased the frequency of spontaneous inhibition with no change in event amplitudes, suggesting a presynaptic change in amacrine cell activity in agreement with previous reports that rod bipolar cells lack D1 receptors. Additionally, we found that D1 receptor activation reduced the amplitude of electrically-evoked responses, showing that D1 receptors can modulate amacrine cells directly. Our results suggest that D1 receptor activation can replicate a large portion, but not all of the effects of light adaptation, likely by modulating release from amacrine cells onto rod bipolar cells.

Kinetics of Recovery of the Dark-adapted Salamander Rod Photoresponse

PubMed Central

Nikonov, S.; Engheta, N.; Pugh, E.N.

1998-01-01

The kinetics of the dark-adapted salamander rod photocurrent response to flashes producing from 10 to 105 photoisomerizations (Φ) were investigated in normal Ringer's solution, and in a choline solution that clamps calcium near its resting level. For saturating intensities ranging from ∼102 to 104 Φ, the recovery phases of the responses in choline were nearly invariant in form. Responses in Ringer's were similarly invariant for saturating intensities from ∼103 to 104 Φ. In both solutions, recoveries to flashes in these intensity ranges translated on the time axis a constant amount (τc) per e-fold increment in flash intensity, and exhibited exponentially decaying “tail phases” with time constant τc. The difference in recovery half-times for responses in choline and Ringer's to the same saturating flash was 5–7 s. Above ∼104 Φ, recoveries in both solutions were systematically slower, and translation invariance broke down. Theoretical analysis of the translation-invariant responses established that τc must represent the time constant of inactivation of the disc-associated cascade intermediate (R*, G*, or PDE*) having the longest lifetime, and that the cGMP hydrolysis and cGMP-channel activation reactions are such as to conserve this time constant. Theoretical analysis also demonstrated that the 5–7-s shift in recovery half-times between responses in Ringer's and in choline is largely (4–6 s) accounted for by the calcium-dependent activation of guanylyl cyclase, with the residual (1–2 s) likely caused by an effect of calcium on an intermediate with a nondominant time constant. Analytical expressions for the dim-flash response in calcium clamp and Ringer's are derived, and it is shown that the difference in the responses under the two conditions can be accounted for quantitatively by cyclase activation. Application of these expressions yields an estimate of the calcium buffering capacity of the rod at rest of ∼20, much lower than previous

Dark-Adapted Chromatic Perimetry for Measuring Rod Visual Fields in Patients with Retinitis Pigmentosa

PubMed Central

Bennett, Lea D.; Klein, Martin; Locke, Kirsten G.; Kiser, Kelly; Birch, David G.

2017-01-01

Purpose Although rod photoreceptors are initially affected in retinitis pigmentosa (RP), the full-field of rod vision is not routinely characterized due to the unavailability of commercial devices detecting rod sensitivity. The purpose of this study was to quantify rod-mediated vision in the peripheral field from patients with RP using a new commercially available perimeter. Methods Participants had one eye dilated and dark-adapted for 45 minutes. A dark-adapted chromatic (DAC) perimeter tested 80 loci 144° horizontally and 72° vertically with cyan stimuli. The number of rod-mediated loci (RML) were analyzed based on normal cone sensitivity (method 1) and associated with full-field electroretinography (ERG) responses by Pearson's r correlation and linear regression. In a second cohort of patients with RP, RML were identified by two-color perimetry (cyan and red; method 2). The two methods for ascribing rod function were compared by Bland-Altman analysis. Results Method 1 RML were correlated with responses to the 0.01 cd.s/m2 flash (P < 0.001), while total sensitivity to the cyan stimulus showed correlation with responses to the 3.0 cd.s/m2 flash (P < 0.0001). Method 2 detected a mean of 10 additional RML compared to method 1. Conclusions Scotopic fields measured with the DAC detected rod sensitivity across the full visual field, even in some patients who had nondetectable rod ERGs. Two-color perimetry is warranted when sensitivity to the cyan stimulus is reduced to ≤20 dB to get a true estimation of rod function. Translational Relevance Many genetic forms of retinitis pigmentosa (RP) are caused by mutations in rod-specific genes. However, treatment trials for patients with RP have relied primarily on photopic (cone-mediated) tests as outcome measures because there are a limited number of available testing methods designed to evaluate rod function. Thus, efficient methods for quantifying rod-mediated vision are needed for the rapidly increasing numbers of

The effect of light on outer segment calcium in salamander rods

PubMed Central

Matthews, Hugh R; Fain, Gordon L

2003-01-01

Calcium acts as a second messenger in vertebrate rods, regulating the recovery phase of the light response and modulating sensitivity during light-adaptation. Since light not only decreases the outer segment calcium concentration ([Ca2+]i) by closing cyclic nucleotide-gated channels but can also increase [Ca2+]i by releasing Ca2+ from buffer sites or intracellular stores, we examined in detail the effect of light and circulating current on [Ca2+]i by making simultaneous measurements of suction pipette current and [Ca2+]i from isolated rods of the salamander Ambystoma tigrinum after incorporation of the fluorescent dye fluo-5F. When the release of Ca2+ is measured in 0 Ca2+−0 Na+ solution, minimising fluxes of Ca2+ across the plasma membrane, it is substantial only for light bright enough to bleach a significant fraction of the photopigment and is restricted to the part of the outer segment in which the bleach occurred. It is unlikely, therefore, to make a large contribution to [Ca2+]i for most of the physiological operating range of the rod. Nevertheless, since release is half-maximal for a bleach of less than 10 %, it cannot be produced by a simple mechanism such as a change in the affinity of a binding site on rhodopsin itself but must instead require some more complex interaction. In Ringer solution, the Ca2+ in the light-releasable pool can be discharged merely by the decrease in [Ca2+]i that occurs as the outer segment channels close. In steady background light or after exposure to saturating illumination, the fraction of Ca2+ in the pool decreases essentially in proportion to [Ca2+]i as if Ca2+ were being removed from a buffer site within the cytoplasm. Furthermore, [Ca2+]i itself changes in proportion to the circulating current, with little evidence for a contribution from Ca2+ release or other mechanisms of Ca2+ homeostasis. This indicates that flux of Ca2+ across the plasma membrane is the major determinant of outer segment Ca2+ concentration within the

Weak endogenous Ca2+ buffering supports sustained synaptic transmission by distinct mechanisms in rod and cone photoreceptors in salamander retina

PubMed Central

Van Hook, Matthew J; Thoreson, Wallace B

2015-01-01

Differences in synaptic transmission between rod and cone photoreceptors contribute to different response kinetics in rod- versus cone-dominated visual pathways. We examined Ca2+ dynamics in synaptic terminals of tiger salamander photoreceptors under conditions that mimicked endogenous buffering to determine the influence on kinetically and mechanistically distinct components of synaptic transmission. Measurements of ICl(Ca) confirmed that endogenous Ca2+ buffering is equivalent to ˜0.05 mmol/L EGTA in rod and cone terminals. Confocal imaging showed that with such buffering, depolarization stimulated large, spatially unconstrained [Ca2+] increases that spread throughout photoreceptor terminals. We calculated immediately releasable pool (IRP) size and release efficiency in rods by deconvolving excitatory postsynaptic currents and presynaptic Ca2+ currents. Peak efficiency of ˜0.2 vesicles/channel was similar to that of cones (˜0.3 vesicles/channel). Efficiency in both cell types was not significantly affected by using weak endogenous Ca2+ buffering. However, weak Ca2+ buffering speeded Ca2+/calmodulin (CaM)-dependent replenishment of vesicles to ribbons in both rods and cones, thereby enhancing sustained release. In rods, weak Ca2+ buffering also amplified sustained release by enhancing CICR and CICR-stimulated release of vesicles at nonribbon sites. By contrast, elevating [Ca2+] at nonribbon sites in cones with weak Ca2+ buffering and by inhibiting Ca2+ extrusion did not trigger additional release, consistent with the notion that exocytosis from cones occurs exclusively at ribbons. The presence of weak endogenous Ca2+ buffering in rods and cones facilitates slow, sustained exocytosis by enhancing Ca2+/CaM-dependent replenishment of ribbons in both rods and cones and by stimulating nonribbon release triggered by CICR in rods. PMID:26416977

Calcium-induced calcium release in rod photoreceptor terminals boosts synaptic transmission during maintained depolarization

PubMed Central

Cadetti, Lucia; Bryson, Eric J.; Ciccone, Cory A.; Rabl, Katalin; Thoreson, Wallace B.

2008-01-01

We examined the contribution of calcium-induced calcium release (CICR) to synaptic transmission from rod photoreceptor terminals. Whole-cell recording and confocal calcium imaging experiments were conducted on rods with intact synaptic terminals in a retinal slice preparation from salamander. Low concentrations of ryanodine stimulated calcium increases in rod terminals, consistent with the presence of ryanodine receptors. Application of strong depolarizing steps (−70 to −10 mV) exceeding 200 ms or longer in duration evoked a wave of calcium that spread across the synaptic terminals of voltage-clamped rods. This secondary calcium increase was blocked by high concentrations of ryanodine, indicating it was due to CICR. Ryanodine (50 μM) had no significant effect on rod calcium current (Ica) although it slightly diminished rod light-evoked voltage responses. Bath application of 50 μM ryanodine strongly inhibited light-evoked currents in horizontal cells. Whether applied extracellularly or delivered into the rod cell through the patch pipette, ryanodine (50 μM) also inhibited excitatory post-synaptic currents (EPSCs) evoked in horizontal cells by depolarizing steps applied to rods. Ryanodine caused a preferential reduction in the later portions of EPSCs evoked by depolarizing steps of 200 ms or longer. These results indicate that CICR enhances calcium increases in rod terminals evoked by sustained depolarization, which in turn acts to boost synaptic exocytosis from rods. PMID:16819987

Rapid kinetics of endocytosis at rod photoreceptor synapses depends upon endocytic load and calcium.

PubMed

Cork, Karlene M; Thoreson, Wallace B

2014-05-01

Release from rods is triggered by the opening of L-type Ca2+ channels that lie beneath synaptic ribbons. After exocytosis, vesicles are retrieved by compensatory endocytosis. Previous work showed that endocytosis is dynamin-dependent in rods but dynamin-independent in cones. We hypothesized that fast endocytosis in rods may also differ from cones in its dependence upon the amount of Ca2+ influx and/or endocytic load. We measured exocytosis and endocytosis from membrane capacitance (C m) changes evoked by depolarizing steps in voltage clamped rods from tiger salamander retinal slices. Similar to cones, the time constant for endocytosis in rods was quite fast, averaging <200 ms. We manipulated Ca2+ influx and the amount of vesicle release by altering the duration and voltage of depolarizing steps. Unlike cones, endocytosis kinetics in rods slowed after increasing Ca2+ channel activation with longer step durations or more strongly depolarized voltage steps. Endocytosis kinetics also slowed as Ca2+ buffering was decreased by replacing BAPTA (10 or 1 mM) with the slower Ca2+ buffer EGTA (5 or 0.5 mM) in the pipette solution. These data provide further evidence that endocytosis mechanisms differ in rods and cones and suggest that endocytosis in rods is regulated by both endocytic load and local Ca2+ levels.

Rapid kinetics of endocytosis at rod photoreceptor synapses depends upon endocytic load and calcium

PubMed Central

CORK, KARLENE M.; THORESON, WALLACE B.

2015-01-01

Release from rods is triggered by the opening of L-type Ca2+ channels that lie beneath synaptic ribbons. After exocytosis, vesicles are retrieved by compensatory endocytosis. Previous work showed that endocytosis is dynamin-dependent in rods but dynamin-independent in cones. We hypothesized that fast endocytosis in rods may also differ from cones in its dependence upon the amount of Ca2+ influx and/or endocytic load. We measured exocytosis and endocytosis from membrane capacitance (Cm) changes evoked by depolarizing steps in voltage clamped rods from tiger salamander retinal slices. Similar to cones, the time constant for endocytosis in rods was quite fast, averaging <200 ms. We manipulated Ca2+ influx and the amount of vesicle release by altering the duration and voltage of depolarizing steps. Unlike cones, endocytosis kinetics in rods slowed after increasing Ca2+ channel activation with longer step durations or more strongly depolarized voltage steps. Endocytosis kinetics also slowed as Ca2+ buffering was decreased by replacing BAPTA (10 or 1 mM) with the slower Ca2+ buffer EGTA (5 or 0.5 mM) in the pipette solution. These data provide further evidence that endocytosis mechanisms differ in rods and cones and suggest that endocytosis in rods is regulated by both endocytic load and local Ca2+ levels. PMID:24735554

Association between retinal thickness measured by spectral-domain optical coherence tomography (OCT) and rod-mediated dark adaptation in non-exudative age-related maculopathy.

PubMed

Clark, Mark E; McGwin, Gerald; Neely, David; Feist, Richard; Mason, John O; Thomley, Martin; White, Milton F; Ozaydin, Bunyamin; Girkin, Christopher A; Owsley, Cynthia

2011-10-01

To examine associations between retinal thickness and rod-mediated dark adaptation in older adults with non-exudative age-related maculopathy (ARM) or normal macular health. A cross-sectional study was conducted with 74 adults ≥ 50 years old from the comprehensive ophthalmology and retina services of an academic eye centre. ARM presence and disease severity in the enrolment eye was defined by the masked grading of stereofundus photos using the Clinical Age-Related Maculopathy grading system. High-definition, spectral-domain optical coherence tomography was used to estimate retinal thickness in a grid of regions in the macula. Rod-mediated dark adaptation, recovery of light sensitivity after a photo-bleach, was measured over a 20-min period for a 500 nm target presented at 5° on the inferior vertical meridian. Main outcomes of interest were retinal thickness in the macula (μm) and parameters of rod-mediated dark adaptation (second slope, third slope, average sensitivity, final sensitivity). In non-exudative disease retinal thickness was decreased in greater disease severity; thinner retina was associated with reductions in average and final rod-mediated sensitivity even after adjustment for age and visual acuity. Impairment in rod-mediated dark adaptation in non-exudative ARM is associated with macular thinning.

Inherited Retinal Degenerative Disease Registry

ClinicalTrials.gov

2017-09-13

Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

Extra-mitochondrial aerobic metabolism in retinal rod outer segments: new perspectives in retinopathies.

PubMed

Panfoli, I; Calzia, D; Ravera, S; Morelli, A M; Traverso, C E

2012-04-01

Vertebrate retinal rods are photoreceptors for dim-light vision. They display extreme sensitivity to light thanks to a specialized subcellular organelle, the rod outer segment. This is filled with a stack of membranous disks, expressing the proteins involved in visual transduction, a very energy demanding process. Our previous proteomic and biochemical studies have shed new light on the chemical energy processes that supply ATP to the outer segment, suggesting the presence of an extra-mitochondrial aerobic metabolism in rod outer segment, devoid of mitochondria, which would account for a quantitatively adequate ATP supply for phototransduction. Here the functional presence of an oxidative phosphorylation in the rod outer limb is examined for its relationship to many physiological and pathological data on the rod outer segment. We hypothesize that the rod outer limb is at risk of oxidative stress, in any case of impairment in the respiratory chain functioning, or of blood supply. In fact, the electron transfer chain is a major source of reactive O(2) species, known to produce severe alteration to the membrane lipids, especially those of the outer segment that are rich in polyunsaturated fatty acids. We propose that the disk membrane may become the target of reactive oxygen species that may be released by the electron transport chain under pathologic conditions. For example, during aging reactive oxygen species production increases, while cellular antioxidant capacity decreases. Also the apoptosis of the rod observed after exposure to bright or continuous illumination can be explained considering that an overfunctioning of phototransduction may damage the disk membrane to a point at which cytochrome c escapes from the intradiskal space, where it is presently supposed to be, activating a putative caspase 9 and the apoptosome. A pathogenic mechanism for many inherited and acquired retinal degenerations, representing a major problem in clinical ophthalmology, is

The retinal rod Na(+)/Ca(2+),K(+) exchanger contains a noncleaved signal sequence required for translocation of the N terminus.

PubMed

McKiernan, C J; Friedlander, M

1999-12-31

The retinal rod Na(+)/Ca(2+),K(+) exchanger (RodX) is a polytopic membrane protein found in photoreceptor outer segments where it is the principal extruder of Ca(2+) ions during light adaptation. We have examined the role of the N-terminal 65 amino acids in targeting, translocation, and integration of the RodX using an in vitro translation/translocation system. cDNAs encoding human RodX and bovine RodX through the first transmembrane domain were correctly targeted and integrated into microsomal membranes; deletion of the N-terminal 65 amino acids (aa) resulted in a translation product that was not targeted or integrated. Deletion of the first 65 aa had no effect on membrane targeting of full-length RodX, but the N-terminal hydrophilic domain no longer translocated. Chimeric constructs encoding the first 65 aa of bovine RodX fused to globin were translocated across microsomal membranes, demonstrating that the sequence could function heterologously. Studies of fresh bovine retinal extracts demonstrated that the first 65 aa are present in the native protein. These data demonstrate that the first 65 aa of RodX constitute an uncleaved signal sequence required for the efficient membrane targeting and proper membrane integration of RodX.

Increased proliferation of late-born retinal progenitor cells by gestational lead exposure delays rod and bipolar cell differentiation.

PubMed

Chaney, Shawnta Y; Mukherjee, Shradha; Giddabasappa, Anand; Rueda, Elda M; Hamilton, W Ryan; Johnson, Jerry E; Fox, Donald A

2016-01-01

Studies of neuronal development in the retina often examine the stages of proliferation, differentiation, and synaptic development, albeit independently. Our goal was to determine if a known neurotoxicant insult to a population of retinal progenitor cells (RPCs) would affect their eventual differentiation and synaptic development. To that end, we used our previously published human equivalent murine model of low-level gestational lead exposure (GLE). Children and animals with GLE exhibit increased scotopic electroretinogram a- and b-waves. Adult mice with GLE exhibit an increased number of late-born RPCs, a prolonged period of RPC proliferation, and an increased number of late-born rod photoreceptors and rod and cone bipolar cells (BCs), with no change in the number of late-born Müller glial cells or early-born neurons. The specific aims of this study were to determine whether increased and prolonged RPC proliferation alters the spatiotemporal differentiation and synaptic development of rods and BCs in early postnatal GLE retinas compared to control retinas. C57BL/6N mouse pups were exposed to lead acetate via drinking water throughout gestation and until postnatal day 10, which is equivalent to the human gestation period for retinal neurogenesis. RT-qPCR, immunohistochemical analysis, and western blots of well-characterized, cell-specific genes and proteins were performed at embryonic and early postnatal ages to assess rod and cone photoreceptor differentiation, rod and BC differentiation and synaptic development, and Müller glial cell differentiation. Real-time quantitative PCR (RT-qPCR) with the rod-specific transcription factors Nrl , Nr2e3 , and Crx and the rod-specific functional gene Rho , along with central retinal confocal studies with anti-recoverin and anti-rhodopsin antibodies, revealed a two-day delay in the differentiation of rod photoreceptors in GLE retinas. Rhodopsin immunoblots supported this conclusion. No changes in glutamine synthetase gene

Stimulus-evoked outer segment changes in rod photoreceptors

NASA Astrophysics Data System (ADS)

Zhao, Xiaohui; Thapa, Damber; Wang, Benquan; Lu, Yiming; Gai, Shaoyan; Yao, Xincheng

2016-06-01

Rod-dominated transient retinal phototropism (TRP) has been recently observed in freshly isolated mouse and frog retinas. Comparative confocal microscopy and optical coherence tomography revealed that the TRP was predominantly elicited from the rod outer segment (OS). However, the biophysical mechanism of rod OS dynamics is still unknown. Mouse and frog retinal slices, which displayed a cross-section of retinal photoreceptors and other functional layers, were used to test the effect of light stimulation on rod OSs. Time-lapse microscopy revealed stimulus-evoked conformational changes of rod OSs. In the center of the stimulated region, the length of the rod OS shrunk, while in the peripheral region, the rod OS swung toward the center region. Our experimental observation and theoretical analysis suggest that the TRP may reflect unbalanced rod disc-shape changes due to localized visible light stimulation.

Stimulus-evoked outer segment changes in rod photoreceptors

PubMed Central

Zhao, Xiaohui; Thapa, Damber; Wang, Benquan; Lu, Yiming; Gai, Shaoyan; Yao, Xincheng

2016-01-01

Abstract. Rod-dominated transient retinal phototropism (TRP) has been recently observed in freshly isolated mouse and frog retinas. Comparative confocal microscopy and optical coherence tomography revealed that the TRP was predominantly elicited from the rod outer segment (OS). However, the biophysical mechanism of rod OS dynamics is still unknown. Mouse and frog retinal slices, which displayed a cross-section of retinal photoreceptors and other functional layers, were used to test the effect of light stimulation on rod OSs. Time-lapse microscopy revealed stimulus-evoked conformational changes of rod OSs. In the center of the stimulated region, the length of the rod OS shrunk, while in the peripheral region, the rod OS swung toward the center region. Our experimental observation and theoretical analysis suggest that the TRP may reflect unbalanced rod disc-shape changes due to localized visible light stimulation. PMID:27334933

Aerobic Glycolysis Is Essential for Normal Rod Function and Controls Secondary Cone Death in Retinitis Pigmentosa.

PubMed

Petit, Lolita; Ma, Shan; Cipi, Joris; Cheng, Shun-Yun; Zieger, Marina; Hay, Nissim; Punzo, Claudio

2018-05-29

Aerobic glycolysis accounts for ∼80%-90% of glucose used by adult photoreceptors (PRs); yet, the importance of aerobic glycolysis for PR function or survival remains unclear. Here, we further established the role of aerobic glycolysis in murine rod and cone PRs. We show that loss of hexokinase-2 (HK2), a key aerobic glycolysis enzyme, does not affect PR survival or structure but is required for normal rod function. Rods with HK2 loss increase their mitochondrial number, suggesting an adaptation to the inhibition of aerobic glycolysis. In contrast, cones adapt without increased mitochondrial number but require HK2 to adapt to metabolic stress conditions such as those encountered in retinitis pigmentosa, where the loss of rods causes a nutrient shortage in cones. The data support a model where aerobic glycolysis in PRs is not a necessity but rather a metabolic choice that maximizes PR function and adaptability to nutrient stress conditions. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by adaptive optics retinal imaging

PubMed Central

Song, Hongxin; Rossi, Ethan A; Stone, Edwin; Latchney, Lisa; Williams, David; Dubra, Alfredo; Chung, Mina

2018-01-01

Purpose Several genes causing autosomal-dominant cone-rod dystrophy (AD-CRD) have been identified. However, the mechanisms by which genetic mutations lead to cellular loss in human disease remain poorly understood. Here we combine genotyping with high-resolution adaptive optics retinal imaging to elucidate the retinal phenotype at a cellular level in patients with AD-CRD harbouring a defect in the GUCA1A gene. Methods Nine affected members of a four-generation AD-CRD pedigree and three unaffected first-degree relatives underwent clinical examinations including visual acuity, fundus examination, Goldmann perimetry, spectral domain optical coherence tomography and electroretinography. Genome-wide scan followed by bidirectional sequencing was performed on all affected participants. High-resolution imaging using a custom adaptive optics scanning light ophthalmoscope (AOSLO) was performed for selected participants. Results Clinical evaluations showed a range of disease severity from normal fundus appearance in teenaged patients to pronounced macular atrophy in older patients. Molecular genetic testing showed a mutation in in GUCA1A segregating with disease. AOSLO imaging revealed that of the two teenage patients with mild disease, one had severe disruption of the photoreceptor mosaic while the other had a normal cone mosaic. Conclusions AOSLO imaging demonstrated variability in the pattern of cone and rod cell loss between two teenage cousins with early AD-CRD, who had similar clinical features and had the identical disease-causing mutation in GUCA1A. This finding suggests that a mutation in GUCA1A does not lead to the same degree of AD-CRD in all patients. Modifying factors may mitigate or augment disease severity, leading to different retinal cellular phenotypes. PMID:29074494

Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by adaptive optics retinal imaging.

PubMed

Song, Hongxin; Rossi, Ethan A; Stone, Edwin; Latchney, Lisa; Williams, David; Dubra, Alfredo; Chung, Mina

2018-01-01

Several genes causing autosomal-dominant cone-rod dystrophy (AD-CRD) have been identified. However, the mechanisms by which genetic mutations lead to cellular loss in human disease remain poorly understood. Here we combine genotyping with high-resolution adaptive optics retinal imaging to elucidate the retinal phenotype at a cellular level in patients with AD-CRD harbouring a defect in the GUCA1A gene. Nine affected members of a four-generation AD-CRD pedigree and three unaffected first-degree relatives underwent clinical examinations including visual acuity, fundus examination, Goldmann perimetry, spectral domain optical coherence tomography and electroretinography. Genome-wide scan followed by bidirectional sequencing was performed on all affected participants. High-resolution imaging using a custom adaptive optics scanning light ophthalmoscope (AOSLO) was performed for selected participants. Clinical evaluations showed a range of disease severity from normal fundus appearance in teenaged patients to pronounced macular atrophy in older patients. Molecular genetic testing showed a mutation in in GUCA1A segregating with disease. AOSLO imaging revealed that of the two teenage patients with mild disease, one had severe disruption of the photoreceptor mosaic while the other had a normal cone mosaic. AOSLO imaging demonstrated variability in the pattern of cone and rod cell loss between two teenage cousins with early AD-CRD, who had similar clinical features and had the identical disease-causing mutation in GUCA1A . This finding suggests that a mutation in GUCA1A does not lead to the same degree of AD-CRD in all patients. Modifying factors may mitigate or augment disease severity, leading to different retinal cellular phenotypes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Metabotropic and ionotropic glutamate receptors regulate calcium channel currents in salamander retinal ganglion cells

PubMed Central

Shen, Wen; Slaughter, Malcolm M

1998-01-01

Glutamate suppressed high-voltage-activated barium currents (IBa,HVA) in tiger salamander retinal ganglion cells. Both ionotropic (iGluR) and metabotropic (mGluR) receptors contributed to this calcium channel inhibition. Trans-ACPD (1-aminocyclopentane-trans-1S,3R-dicarboxylic acid), a broad-spectrum metabotropic glutamate receptor agonist, suppressed a dihydropyridine-sensitive barium current. Kainate, an ionotropic glutamate receptor agonist, reduced an ω-conotoxin GVIA-sensitive current. The relative effectiveness of selective agonists indicated that the predominant metabotropic receptor was the L-2-amino-4-phosphonobutyrate (l-AP4)-sensitive, group III receptor. This receptor reversed the action of forskolin, but this was not responsible for calcium channel suppression. l-AP4 raised internal calcium concentration. Antagonists of phospholipase C, inositol trisphosphate (IP3) receptors and ryanodine receptors inhibited the action of metabotropic agonists, indicating that group III receptor transduction was linked to this pathway. The action of kainate was partially suppressed by BAPTA, by calmodulin antagonists and by blockers of calmodulin-dependent phosphatase. Suppression by kainate of the calcium channel current was more rapid when calcium was the charge carrier, instead of barium. The results indicate that calcium influx through kainate-sensitive glutamate receptors can activate calmodulin, which stimulates phosphatases that may directly suppress voltage-sensitive calcium channels. Thus, ionotropic and metabotropic glutamate receptors inhibit distinct calcium channels. They could act synergistically, since both increase internal calcium. These pathways provide negative feedback that can reduce calcium influx when ganglion cells are depolarized. PMID:9660896

Highly efficient retinal metabolism in cones

PubMed Central

Miyazono, Sadaharu; Shimauchi-Matsukawa, Yoshie; Tachibanaki, Shuji; Kawamura, Satoru

2008-01-01

After bleaching of visual pigment in vertebrate photoreceptors, all-trans retinal is reduced to all-trans retinol by retinol dehydrogenases (RDHs). We investigated this reaction in purified carp rods and cones, and we found that the reducing activity toward all-trans retinal in the outer segment (OS) of cones is >30 times higher than that of rods. The high activity of RDHs was attributed to high content of RDH8 in cones. In the inner segment (IS) in both rods and cones, RDH8L2 and RDH13 were found to be the major enzymes among RDH family proteins. We further found a previously undescribed and effective pathway to convert 11-cis retinol to 11-cis retinal in cones: this oxidative conversion did not require NADP+ and instead was coupled with reduction of all-trans retinal to all-trans retinol. The activity was >50 times effective than the oxidizing activity of RDHs that require NADP+. These highly effective reactions of removal of all-trans retinal by RDH8 and production of 11-cis retinal by the coupling reaction are probably the underlying mechanisms that ensure effective visual pigment regeneration in cones that function under much brighter light conditions than rods. PMID:18836074

The TRPM1 Channel Is Required for Development of the Rod ON Bipolar Cell-AII Amacrine Cell Pathway in the Retinal Circuit.

PubMed

Kozuka, Takashi; Chaya, Taro; Tamalu, Fuminobu; Shimada, Mariko; Fujimaki-Aoba, Kayo; Kuwahara, Ryusuke; Watanabe, Shu-Ichi; Furukawa, Takahisa

2017-10-11

Neurotransmission plays an essential role in neural circuit formation in the central nervous system (CNS). Although neurotransmission has been recently clarified as a key modulator of retinal circuit development, the roles of individual synaptic transmissions are not yet fully understood. In the current study, we investigated the role of neurotransmission from photoreceptor cells to ON bipolar cells in development using mutant mouse lines of both sexes in which this transmission is abrogated. We found that deletion of the ON bipolar cation channel TRPM1 results in the abnormal contraction of rod bipolar terminals and a decreased number of their synaptic connections with amacrine cells. In contrast, these histological alterations were not caused by a disruption of total glutamate transmission due to loss of the ON bipolar glutamate receptor mGluR6 or the photoreceptor glutamate transporter VGluT1. In addition, TRPM1 deficiency led to the reduction of total dendritic length, branch numbers, and cell body size in AII amacrine cells. Activated Goα, known to close the TRPM1 channel, interacted with TRPM1 and induced the contraction of rod bipolar terminals. Furthermore, overexpression of Channelrhodopsin-2 partially rescued rod bipolar cell development in the TRPM1 -/- retina, whereas the rescue effect by a constitutively closed form of TRPM1 was lower than that by the native form. Our results suggest that TRPM1 channel opening is essential for rod bipolar pathway establishment in development. SIGNIFICANCE STATEMENT Neurotransmission has been recognized recently as a key modulator of retinal circuit development in the CNS. However, the roles of individual synaptic transmissions are not yet fully understood. In the current study, we focused on neurotransmission between rod photoreceptor cells and rod bipolar cells in the retina. We used genetically modified mouse models which abrogate each step of neurotransmission: presynaptic glutamate release, postsynaptic glutamate

Characterisation of the canine rod-cone dysplasia type one gene (rod photoreceptor cGMP phosphodiesterase beta subunit (PDEB)) - a model for human retinitis pigmentosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clements, P.J.M.; Gregory, C.Y.; Petersen-Jones, S.M.

1994-09-01

Rod-cone dysplasia type one (rod-1) is an early onset, autosomal recessive retinal dystrophy segregating in the Irish setter breed. It is a model for certain forms of human autosomal recessive retinitis pigmentosa (arRP) caused by mutations in the same gene, PDEB. We confirmed the codon 807 Trp to Stop mutation and were the first to show cosegregation of the mutant allele with disease in a pedigree. We believe that this currently represents the best animal model available for some aspects of arRP, since canine tissues are relatively easy to access compared to human and yet the canine eye is ofmore » comparable size, unlike that of the rd mouse. This facilitates therapeutic intervention particularly at the subretinal level. In order to more fully investigate this model we have been characterizing the PDEB gene in the normal dog. Using PCR we have partially mapped the intron/exon structure, demonstrating a very high degree of evolutionary conservation with the mouse and human genes. RT-PCR has been used to reveal expression in a variety of neural and non-neural tissues. A PCR product spanning exons 19 to 22 (which also contains the site for the rcd-1 mutation) is detected in retina but also in tissues such as visual cortex, cerebral cortex, cerebellum, lateral geniculate nucleus, adrenal gland, lung, kidney and ovary. All of these tissues gave a negative result with primers for rds/peripherin, a gene which is expressed in rods and cones. This raises interesting questions about the regulation of PDEB transcripts which is initially being investigated by Northern analysis. In addition, anchored PCR techniques have generated upstream genomic sequences and we are currently mapping the 5{prime} extent of the mRNA transcript in the retina. This will facilitate the analysis of potential upstream promoter elements involved in directing expression.« less

Photocurrents in retinal rods of pigeons (Columba livia): kinetics and spectral sensitivity.

PubMed Central

Palacios, A G; Goldsmith, T H

1993-01-01

1. Membrane photocurrents were recorded from outer segments of isolated retinal rods of pigeons (Columba livia), the first such measurements on the photoreceptors of a bird. The amplitude of the response to 20 ms flashes of narrow wavelength bands of light increases linearly with intensity at low photon fluxes and saturates at higher intensities. The maximum (saturating) photocurrent observed in forty-nine rod cells was 50 pA. Larger responses with less variability in the intensity for half-maximal responses were observed when the physiological saline contained 20 mM bicarbonate (in addition to Hepes buffer). 2. The dependence of peak amplitude on intensity is well fitted by an exponential function; it is usually less well fitted by the Michaelis-Menten (Naka-Rushton) equation. 3. In the presence of bicarbonate, the average sensitivity of pigeon rods to dim flashes was 0.56 pA photon-1 microns -2. The effective collecting area per photon was 1.8 microns 2. About 83 +/- 26 (mean +/- S.D.) photoisomerizations were required for a half-saturating response. 4. The response kinetics of rods to dim flashes can be reasonably well described by a series of four to five either Poisson or independent filters. The time to peak, measured from the mid-point of a 20 ms flash, was 319 +/- 83 ms (mean +/- S.D.). The integration time of the response was 851 +/- 86 ms (mean +/- S.D.) with bicarbonate present and 572 +/- 126 ms in the absence of bicarbonate. The responses of pigeon rods appear to be slower than those of mammals at the same temperature. The fraction of current suppressed by a single photoisomerization is smaller in pigeon than in mammalian rods by a factor of at least two. 5. The spectral sensitivity function was measured between 680 and 330 nm. The maximum at about 505 nm (range 497-508 nm) corresponds to the alpha-band of a vertebrate rhodopsin and agrees with previous behavioural measurements of scotopic sensitivity of pigeons as well as the absorption spectrum of

Microarray-based mutation analysis of the ABCA4 (ABCR) gene in autosomal recessive cone-rod dystrophy and retinitis pigmentosa.

PubMed

Klevering, B Jeroen; Yzer, Suzanne; Rohrschneider, Klaus; Zonneveld, Marijke; Allikmets, Rando; van den Born, L Ingeborgh; Maugeri, Alessandra; Hoyng, Carel B; Cremers, Frans P M

2004-12-01

Mutations in the ABCA4 gene have been associated with autosomal recessive Stargardt disease (STGD1), cone-rod dystrophy (CRD), and retinitis pigmentosa (RP). We employed a recently developed genotyping microarray, the ABCR400-chip, to search for known ABCA4 mutations in patients with isolated or autosomal recessive CRD (54 cases) or RP (90 cases). We performed detailed ophthalmologic examinations and identified at least one ABCA4 mutation in 18 patients (33%) with CRD and in five patients (5.6%) with RP. Single-strand conformation polymorphism (SSCP) analysis and subsequent DNA sequencing revealed four novel missense mutations (R24C, E161K, P597S, G618E) and a novel 1-bp deletion (5888delG). Ophthalmoscopic abnormalities in CRD patients ranged from minor granular pigmentary changes in the posterior pole to widespread atrophy. In 12 patients with recordable electroretinogram (ERG) tracings, a cone-rod pattern was detected. Three patients demonstrated progression from a retinal dystrophy resembling STGD1 to a more widespread degeneration, and were subsequently diagnosed as CRD. In addition to a variable degree of atrophy, all RP patients displayed ophthalmologic characteristics of classic RP. When detectable, ERG recordings in these patients demonstrated rod-cone patterns of photoreceptor degeneration. In conclusion, in this study, we show that the ABCA4 mutation chip is an efficient first screening tool for arCRD.

Functional Optical Coherence Tomography Enables In Vivo Physiological Assessment of Retinal Rod and Cone Photoreceptors

PubMed Central

Zhang, Qiuxiang; Lu, Rongwen; Wang, Benquan; Messinger, Jeffrey D.; Curcio, Christine A.; Yao, Xincheng

2015-01-01

Transient intrinsic optical signal (IOS) changes have been observed in retinal photoreceptors, suggesting a unique biomarker for eye disease detection. However, clinical deployment of IOS imaging is challenging due to unclear IOS sources and limited signal-to-noise ratios (SNRs). Here, by developing high spatiotemporal resolution optical coherence tomography (OCT) and applying an adaptive algorithm for IOS processing, we were able to record robust IOSs from single-pass measurements. Transient IOSs, which might reflect an early stage of light phototransduction, are consistently observed in the photoreceptor outer segment almost immediately (<4 ms) after retinal stimulation. Comparative studies of dark- and light-adapted retinas have demonstrated the feasibility of functional OCT mapping of rod and cone photoreceptors, promising a new method for early disease detection and improved treatment of diseases such as age-related macular degeneration (AMD) and other eye diseases that can cause photoreceptor damage. PMID:25901915

Functional Optical Coherence Tomography Enables In Vivo Physiological Assessment of Retinal Rod and Cone Photoreceptors

NASA Astrophysics Data System (ADS)

Zhang, Qiuxiang; Lu, Rongwen; Wang, Benquan; Messinger, Jeffrey D.; Curcio, Christine A.; Yao, Xincheng

2015-04-01

Transient intrinsic optical signal (IOS) changes have been observed in retinal photoreceptors, suggesting a unique biomarker for eye disease detection. However, clinical deployment of IOS imaging is challenging due to unclear IOS sources and limited signal-to-noise ratios (SNRs). Here, by developing high spatiotemporal resolution optical coherence tomography (OCT) and applying an adaptive algorithm for IOS processing, we were able to record robust IOSs from single-pass measurements. Transient IOSs, which might reflect an early stage of light phototransduction, are consistently observed in the photoreceptor outer segment almost immediately (<4 ms) after retinal stimulation. Comparative studies of dark- and light-adapted retinas have demonstrated the feasibility of functional OCT mapping of rod and cone photoreceptors, promising a new method for early disease detection and improved treatment of diseases such as age-related macular degeneration (AMD) and other eye diseases that can cause photoreceptor damage.

X-linked dominant cone-rod degeneration: Linkage mapping of a new locus for retinitis pigmentosa (RP15) to Xp22.13-p22.11

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuire, R.E.; Sullivan, L.S.; Daiger, S.P.

1995-07-01

Retinitis pigmentosa is the name given to a heterogeneous group of hereditary retinal degenerations characterized by progressive visual field loss, pigmentary changes of the retina, abnormal electroretinograms, and, frequently, night blindness. In this study, we investigated a family with dominant cone-rod degeneration, a variant form of retinitis pigmentosa. We used microsatellite markers to test for linkage to the disease locus and exluded all mapped autosomal loci. However, a marker from the short arm of the X chromosome, DXS989, showed 0% recombination to the disease locus, with a maximum lod (log-odds) score of 3.3. On the basis of this marker, themore » odds favoring X-linked dominant versus autosomal dominant inheritance are > 10{sup 5}:1. Haplotype analysis using an additional nine microsatellite markers places the disease locus in the Xp22.13-p22.11 region and excludes other X-linked disease loci causing retinal degeneration. The clinical expression of the retinal degeneration is consistent with X-linked dominant inheritance with milder, variable effects of Lyonization affecting expression in females. On the basis of these data we propose that this family has a novel form of dominant, X-linked cone-rod degeneration with the gene symbol {open_quotes}RP15{close_quotes}. 17 refs., 2 figs., 4 tabs.« less

Longitudinal assessment of retinal structure and function reveals a rod-cone degeneration in a guinea pig model initially presented as night blind.

PubMed

Racine, Julie; Joly, Sandrine; Lachapelle, Pierre

2011-08-01

We have previously reported a naturally occurring retinopathy in a population of guinea pigs, where the affected animals presented a defect of the rod-mediated vision. The purpose of this study was to investigate if the mutants were affected with a stationary or degenerative retinopathy and to identify the cellular origin of this unique disorder. Electroretinogram (ERG) [postnatal day 1 (P1) to P450], light (LM) and electron microscopy (EM) [P5, P150, P450], and immunohistochemistry [P30, P150, P450] were evaluated from normal and mutant animals. Irrespective of age, the scotopic ERGs of mutants could only be evoked by bright flashes, and the resulting ERGs were of photopic waveform. Interestingly, the amplitude of the cone and the rod/cone a-waves was always of smaller amplitude in mutants, but this difference tended to decrease with age. In contrast, the b-waves were of larger amplitude than normal in photopic ERGs obtained prior to age 25 (days) and prior to age 10 for rod/cone ERGs. LM revealed, in mutants, an absence of the outer segment layer (OSL) with a reduction in the outer nuclear layer (ONL) thickness. EM disclosed the presence of cone outer segment (OS) while no rod OS could be evidenced. Immunohistochemistry revealed the presence of rhodopsin, both cone opsins as well as normal synaptophysin immunoreactivity. Finally, neither the retinal structure nor the function in the mutants achieved normal development. Results suggest that mutant animals are suffering from a degenerative retinal disorder that affects the structure and function of rods and cones.

Invasive Asian Earthworms Negatively Impact Keystone Terrestrial Salamanders.

PubMed

Ziemba, Julie L; Hickerson, Cari-Ann M; Anthony, Carl D

2016-01-01

Asian pheretimoid earthworms (e.g. Amynthas and Metaphire spp.) are invading North American forests and consuming the vital detrital layer that forest floor biota [including the keystone species Plethodon cinereus (Eastern Red-backed Salamander)], rely on for protection, food, and habitat. Plethodon cinereus population declines have been associated with leaf litter loss following the invasion of several exotic earthworm species, but there have been few studies on the specific interactions between pheretimoid earthworms and P. cinereus. Since some species of large and active pheretimoids spatially overlap with salamanders beneath natural cover objects and in detritus, they may distinctively compound the negative consequences of earthworm-mediated resource degradation by physically disturbing important salamander activities (foraging, mating, and egg brooding). We predicted that earthworms would exclude salamanders from high quality microhabitat, reduce foraging efficiency, and negatively affect salamander fitness. In laboratory trials, salamanders used lower quality microhabitat and consumed fewer flies in the presence of earthworms. In a natural field experiment, conducted on salamander populations from "non-invaded" and "pheretimoid invaded" sites in Ohio, salamanders and earthworms shared cover objects ~60% less than expected. Earthworm abundance was negatively associated with juvenile and male salamander abundance, but had no relationship with female salamander abundance. There was no effect of pheretimoid invasion on salamander body condition. Juvenile and non-resident male salamanders do not hold stable territories centered beneath cover objects such as rocks or logs, which results in reduced access to prey, greater risk of desiccation, and dispersal pressure. Habitat degradation and physical exclusion of salamanders from cover objects may hinder juvenile and male salamander performance, ultimately reducing recruitment and salamander abundance following Asian

Invasive Asian Earthworms Negatively Impact Keystone Terrestrial Salamanders

PubMed Central

Ziemba, Julie L.

2016-01-01

Asian pheretimoid earthworms (e.g. Amynthas and Metaphire spp.) are invading North American forests and consuming the vital detrital layer that forest floor biota [including the keystone species Plethodon cinereus (Eastern Red-backed Salamander)], rely on for protection, food, and habitat. Plethodon cinereus population declines have been associated with leaf litter loss following the invasion of several exotic earthworm species, but there have been few studies on the specific interactions between pheretimoid earthworms and P. cinereus. Since some species of large and active pheretimoids spatially overlap with salamanders beneath natural cover objects and in detritus, they may distinctively compound the negative consequences of earthworm-mediated resource degradation by physically disturbing important salamander activities (foraging, mating, and egg brooding). We predicted that earthworms would exclude salamanders from high quality microhabitat, reduce foraging efficiency, and negatively affect salamander fitness. In laboratory trials, salamanders used lower quality microhabitat and consumed fewer flies in the presence of earthworms. In a natural field experiment, conducted on salamander populations from “non-invaded” and “pheretimoid invaded” sites in Ohio, salamanders and earthworms shared cover objects ~60% less than expected. Earthworm abundance was negatively associated with juvenile and male salamander abundance, but had no relationship with female salamander abundance. There was no effect of pheretimoid invasion on salamander body condition. Juvenile and non-resident male salamanders do not hold stable territories centered beneath cover objects such as rocks or logs, which results in reduced access to prey, greater risk of desiccation, and dispersal pressure. Habitat degradation and physical exclusion of salamanders from cover objects may hinder juvenile and male salamander performance, ultimately reducing recruitment and salamander abundance

Rod- versus cone-driven ERGs at different stimulus sizes in normal subjects and retinitis pigmentosa patients.

PubMed

Aher, Avinash J; McKeefry, Declan J; Parry, Neil R A; Maguire, John; Murray, I J; Tsai, Tina I; Huchzermeyer, Cord; Kremers, Jan

2018-02-01

To study how rod- and cone-driven responses depend on stimulus size in normal subjects and patients with retinitis pigmentosa (RP), and to show that comparisons between responses to full-field (FF) and smaller stimuli can be useful in diagnosing and monitoring disorders of the peripheral retina without the need for lengthy dark adaptation periods. The triple silent substitution technique was used to isolate L-cone-, M-cone- and rod-driven ERGs with 19, 18 and 33% photoreceptor contrasts, respectively, under identical mean luminance conditions. Experiments were conducted on five normal subjects and three RP patients. ERGs on control subjects were recorded at nine different temporal frequencies (between 2 and 60 Hz) for five different stimulus sizes: FF, 70°, 60°, 50° and 40° diameter circular stimuli. Experiments on RP patients involved rod- and L-cone-driven ERG measurements with FF and 40° stimuli at 8 and 48 Hz. Response amplitudes were defined as those of the first harmonic component after Fourier analysis. In normal subjects, rod-driven responses displayed a fundamentally different behavior than cone-driven responses, particularly at low temporal frequencies. At low and intermediate temporal frequencies (≤ 12 Hz), rod-driven signals increased by a factor of about four when measured with smaller stimuli. In contrast, L- and M-cone-driven responses in this frequency region did not change substantially with stimulus size. At high temporal frequencies (≥ 24 Hz), both rod- and cone-driven response amplitudes decreased with decreasing stimulus size. Signals obtained from rod-isolating stimuli under these conditions are likely artefactual. Interestingly, in RP patients, both rod-driven and L-cone-driven ERGs were similar using 40° and FF stimuli. The increased responses with smaller stimuli in normal subjects to rod-isolating stimuli indicate that a fundamentally different mechanism drives the ERGs in comparison with the cone-driven responses. We

Not just signal shutoff: the protective role of arrestin-1 in rod cells.

PubMed

Sommer, Martha E; Hofmann, Klaus Peter; Heck, Martin

2014-01-01

The retinal rod cell is an exquisitely sensitive single-photon detector that primarily functions in dim light (e.g., moonlight). However, rod cells must routinely survive light intensities more than a billion times greater (e.g., bright daylight). One serious challenge to rod cell survival in daylight is the massive amount of all-trans-retinal that is released by Meta II, the light-activated form of the photoreceptor rhodopsin. All-trans-retinal is toxic, and its condensation products have been implicated in disease. Our recent work has developed the concept that rod arrestin (arrestin-1), which terminates Meta II signaling, has an additional role in protecting rod cells from the consequences of bright light by limiting free all-trans-retinal. In this chapter we will elaborate upon the molecular mechanisms by which arrestin-1 serves as both a single-photon response quencher as well as an instrument of rod cell survival in bright light. This discussion will take place within the framework of three distinct functional modules of vision: signal transduction, the retinoid cycle, and protein translocation.

Concentric retinitis pigmentosa: clinicopathologic correlations.

PubMed

Milam, A H; De Castro, E B; Smith, J E; Tang, W X; John, S K; Gorin, M B; Stone, E M; Aguirre, G D; Jacobson, S G

2001-10-01

Progressive concentric (centripetal) loss of vision is one pattern of visual field loss in retinitis pigmentosa. This study provides the first clinicopathologic correlations for this form of retinitis pigmentosa. A family with autosomal dominant concentric retinitis pigmentosa was examined clinically and with visual function tests. A post-mortem eye of an affected 94 year old family member was processed for histopathology and immunocytochemistry with retinal cell specific antibodies. Unrelated simplex/multiplex patients with concentric retinitis pigmentosa were also examined. Affected family members of the eye donor and patients from the other families had prominent peripheral pigmentary retinopathy with more normal appearing central retina, good visual acuity, concentric field loss, normal or near normal rod and cone sensitivity within the preserved visual field, and reduced rod and cone electroretinograms. The eye donor, at age 90, had good acuity and function in a central island. Grossly, the central region of the donor retina appeared thinned but otherwise normal, while the far periphery contained heavy bone spicule pigment. Microscopically the central retina showed photoreceptor outer segment shortening and some photoreceptor cell loss. The mid periphery had a sharp line of demarcation where more central photoreceptors were near normal except for very short outer segments and peripheral photoreceptors were absent. Rods and cones showed abrupt loss of outer segments and cell death at this interface. It is concluded that concentric retinitis pigmentosa is a rare but recognizable phenotype with slowly progressive photoreceptor death from the far periphery toward the central retina. The disease is retina-wide but shows regional variation in severity of degeneration; photoreceptor death is severe in the peripheral retina with an abrupt edge between viable and degenerate photoreceptors. Peripheral to central gradients of unknown retinal molecule(s) may be defective

Light responses in rods of vitamin A-deprived Xenopus.

PubMed

Solessio, Eduardo; Umino, Yumiko; Cameron, David A; Loew, Ellis; Engbretson, Gustav A; Knox, Barry E; Barlow, Robert B

2009-09-01

Accumulation of free opsin by mutations in rhodopsin or insufficiencies in the visual cycle can lead to retinal degeneration. Free opsin activates phototransduction; however, the link between constitutive activation and retinal degeneration is unclear. In this study, the photoresponses of Xenopus rods rendered constitutively active by vitamin A deprivation were examined. Unlike their mammalian counterparts, Xenopus rods do not degenerate. Contrasting phototransduction in vitamin A-deprived Xenopus rods with phototransduction in constitutively active mammalian rods may provide new understanding of the mechanisms that lead to retinal degeneration. The photocurrents of Xenopus tadpole rods were measured with suction electrode recordings, and guanylate cyclase activity was measured with the IBMX (3-isobutyl-1-methylxanthine) jump technique. The amount of rhodopsin in rods was determined by microspectrophotometry. The vitamin A-deprived rod outer segments were 60% to 70% the length and diameter of the rods in age-matched animals. Approximately 90% of its opsin content was in the free or unbound form. Analogous to bleaching adaptation, the photoresponses were desensitized (10- to 20-fold) and faster. Unlike bleaching adaptation, the vitamin A-deprived rods maintained near normal saturating (dark) current densities by developing abnormally high rates of cGMP synthesis. Their rate of cGMP synthesis in the dark (15 seconds(-1)) was twofold greater than the maximum levels attainable by control rods ( approximately 7 seconds(-1)). Preserving circulating current density and response range appears to be an important goal for rod homeostasis. However, the compensatory changes associated with vitamin A deprivation in Xenopus rods come at the high metabolic cost of a 15-fold increase in basal ATP consumption.

Influence of bacterial toxins on the GTPase activity of transducin from bovine retinal rod outer segments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rybin, V.O.; Gureeva, A.A.

1986-05-10

The action of cholera toxin, capable of ADP-ribosylation of the activator N/sub s/ protein, and pertussis toxin, capable of ADP-ribosylation of the inhibitor N/sub i/ protein of the adenylate cyclase complex, on transducin, the GTP-binding protein of the rod outer segments of the retina, was investigated. It was shown that under the action of pertussis and cholera toxins, the GTPase activity of transducin is inhibited. Pertussin toxin inhibits the GTPase of native retinal rod outer segments by 30-40%, while GTPase of homogeneous transducin produces a 70-80% inhibition. The action of toxins on transducin depends on the presence and nature ofmore » the guanylic nucleotide with which incubation is performed. On the basis of the data obtained it is suggested that pertussis toxin interacts with pretransducin and with the transducin-GDP complex, while cholera toxin ADP-ribosylates the transducin-GTP complex and does not act on transducin lacking GTP.« less

Duration of spiral aftereffect as a function of retinal size, retinal place, and hemiretinal transfer.

DOT National Transportation Integrated Search

1964-01-01

This experiment has shown that, although both rods and cones mediate the spiral aftereffect, cone areas give a larger response. Increasing size of the retinal image results in longer durations of SAE but rods are more affected by this increase than a...

Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina.

PubMed

White, David T; Sengupta, Sumitra; Saxena, Meera T; Xu, Qingguo; Hanes, Justin; Ding, Ding; Ji, Hongkai; Mumm, Jeff S

2017-05-02

Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis. Neutrophils displayed no reactivity to rod cell loss. Peripheral macrophage cells responded to rod cell loss, as evidenced by morphological transitions and increased migration, but did not enter the retina. Retinal microglia displayed multiple hallmarks of immune cell activation: increased migration, translocation to the photoreceptor cell layer, proliferation, and phagocytosis of dying cells. To test function during rod cell regeneration, we coablated microglia and rod cells or applied immune suppression and quantified the kinetics of ( i ) rod cell clearance, ( ii ) MG/progenitor cell proliferation, and ( iii ) rod cell replacement. Coablation and immune suppressants applied before cell loss caused delays in MG/progenitor proliferation rates and slowed the rate of rod cell replacement. Conversely, immune suppressants applied after cell loss had been initiated led to accelerated photoreceptor regeneration kinetics, possibly by promoting rapid resolution of an acute immune response. Our findings suggest that microglia control MG responsiveness to photoreceptor loss and support the development of immune-targeted therapeutic strategies for reversing cell loss associated with degenerative retinal conditions.

Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina

PubMed Central

White, David T.; Sengupta, Sumitra; Saxena, Meera T.; Xu, Qingguo; Hanes, Justin; Ding, Ding; Ji, Hongkai

2017-01-01

Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration—i.e., selective cell-loss paradigms akin to degenerative disease—are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis. Neutrophils displayed no reactivity to rod cell loss. Peripheral macrophage cells responded to rod cell loss, as evidenced by morphological transitions and increased migration, but did not enter the retina. Retinal microglia displayed multiple hallmarks of immune cell activation: increased migration, translocation to the photoreceptor cell layer, proliferation, and phagocytosis of dying cells. To test function during rod cell regeneration, we coablated microglia and rod cells or applied immune suppression and quantified the kinetics of (i) rod cell clearance, (ii) MG/progenitor cell proliferation, and (iii) rod cell replacement. Coablation and immune suppressants applied before cell loss caused delays in MG/progenitor proliferation rates and slowed the rate of rod cell replacement. Conversely, immune suppressants applied after cell loss had been initiated led to accelerated photoreceptor regeneration kinetics, possibly by promoting rapid resolution of an acute immune response. Our findings suggest that microglia control MG responsiveness to photoreceptor loss and support the development of immune-targeted therapeutic strategies for reversing cell loss associated with degenerative retinal conditions. PMID:28416692

Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope

PubMed Central

Dubra, Alfredo; Sulai, Yusufu; Norris, Jennifer L.; Cooper, Robert F.; Dubis, Adam M.; Williams, David R.; Carroll, Joseph

2011-01-01

The rod photoreceptors are implicated in a number of devastating retinal diseases. However, routine imaging of these cells has remained elusive, even with the advent of adaptive optics imaging. Here, we present the first in vivo images of the contiguous rod photoreceptor mosaic in nine healthy human subjects. The images were collected with three different confocal adaptive optics scanning ophthalmoscopes at two different institutions, using 680 and 775 nm superluminescent diodes for illumination. Estimates of photoreceptor density and rod:cone ratios in the 5°–15° retinal eccentricity range are consistent with histological findings, confirming our ability to resolve the rod mosaic by averaging multiple registered images, without the need for additional image processing. In one subject, we were able to identify the emergence of the first rods at approximately 190 μm from the foveal center, in agreement with previous histological studies. The rod and cone photoreceptor mosaics appear in focus at different retinal depths, with the rod mosaic best focus (i.e., brightest and sharpest) being at least 10 μm shallower than the cones at retinal eccentricities larger than 8°. This study represents an important step in bringing high-resolution imaging to bear on the study of rod disorders. PMID:21750765

LTR Retrotransposons Contribute to Genomic Gigantism in Plethodontid Salamanders

PubMed Central

Sun, Cheng; Shepard, Donald B.; Chong, Rebecca A.; López Arriaza, José; Hall, Kathryn; Castoe, Todd A.; Feschotte, Cédric; Pollock, David D.; Mueller, Rachel Lockridge

2012-01-01

Among vertebrates, most of the largest genomes are found within the salamanders, a clade of amphibians that includes 613 species. Salamander genome sizes range from ∼14 to ∼120 Gb. Because genome size is correlated with nucleus and cell sizes, as well as other traits, morphological evolution in salamanders has been profoundly affected by genomic gigantism. However, the molecular mechanisms driving genomic expansion in this clade remain largely unknown. Here, we present the first comparative analysis of transposable element (TE) content in salamanders. Using high-throughput sequencing, we generated genomic shotgun data for six species from the Plethodontidae, the largest family of salamanders. We then developed a pipeline to mine TE sequences from shotgun data in taxa with limited genomic resources, such as salamanders. Our summaries of overall TE abundance and diversity for each species demonstrate that TEs make up a substantial portion of salamander genomes, and that all of the major known types of TEs are represented in salamanders. The most abundant TE superfamilies found in the genomes of our six focal species are similar, despite substantial variation in genome size. However, our results demonstrate a major difference between salamanders and other vertebrates: salamander genomes contain much larger amounts of long terminal repeat (LTR) retrotransposons, primarily Ty3/gypsy elements. Thus, the extreme increase in genome size that occurred in salamanders was likely accompanied by a shift in TE landscape. These results suggest that increased proliferation of LTR retrotransposons was a major molecular mechanism contributing to genomic expansion in salamanders. PMID:22200636

Physiological and morphological characterization of ganglion cells in the salamander retina

PubMed Central

Wang, Jing; Jacoby, Roy; Wu, Samuel M.

2016-01-01

Retinal ganglion cells (RGCs) integrate visual information from the retina and transmit collective signals to the brain. A systematic investigation of functional and morphological characteristics of various types of RGCs is important to comprehensively understand how the visual system encodes and transmits information via various RGC pathways. This study evaluated both physiological and morphological properties of 67 RGCs in dark-adapted flat-mounted salamander retina by examining light-evoked cation and chloride current responses via voltage-clamp recordings and visualizing morphology by Lucifer yellow fluorescence with a confocal microscope. Six groups of RGCs were described: asymmetrical ON–OFF RGCs, symmetrical ON RGCs, OFF RGCs, and narrow-, medium- and wide-field ON–OFF RGCs. Dendritic field diameters of RGCs ranged 102–490 µm: narrow field (<200 µm, 31% of RGCs), medium field (200–300 µm, 45%) and wide field (>300 µm, 24%). Dendritic ramification patterns of RGCs agree with the sub-lamina A/B rule. 34% of RGCs were monostratified, 24% bistratified and 42% diffusely stratified. 70% of ON RGCs and OFF RGCs were monostratified. Wide-field RGCs were diffusely stratified. 82% of RGCs generated light-evoked ON–OFF responses, while 11% generated ON responses and 7% OFF responses. Response sensitivity analysis suggested that some RGCs obtained separated rod/cone bipolar cell inputs whereas others obtained mixed bipolar cell inputs. 25% of neurons in the RGC layer were displaced amacrine cells. Although more types may be defined by more refined classification criteria, this report is to incorporate more physiological properties into RGC classification. PMID:26731645

Northwestern salamanders Ambystoma gracile in mountain lakes: record oviposition depths among salamanders

USGS Publications Warehouse

Hoffman, R.; Pearl, C.A.; Larson, G.L.; Samora, B.

2012-01-01

Oviposition timing, behaviors, and microhabitats of ambystomatid salamanders vary considerably (Egan and Paton 2004; Figiel and Semlitsch 1995; Howard and Wallace 1985; Mac-Cracken 2007). Regardless of species, however, females typically oviposit using sites conducive to embryo development and survival. For example, the results of an experiment by Figiel and Semlitsch (1995) on Ambystoma opacum (Marbled Salamander) oviposition indicated that females actively selected sites that were under grass clumps in wet versus dry treatments, and surmised that environmental conditions such as humidity, moisture, and temperature contributed to their results. Other factors associated with ambystomatid oviposition and embryo survival include water temperature (Anderson 1972; Brown 1976), dissolved oxygen concentration (Petranka et al. 1982; Sacerdote and King 2009), oviposition depth (Dougherty et al. 2005; Egan and Paton 2004), and oviposition attachment structures such as woody vegetation (McCracken 2007; Nussbaum et al. 1983). Resetarits (1996), in creating a model of oviposition site selection for anuran amphibians, hypothesized that oviparous organisms were also capable of modifying oviposition behavior and site selection to accommodate varying habitat conditions and to minimize potential negative effects of environmental stressors. Kats and Sih (1992), investigating the oviposition of Ambystoma barbouri (Streamside Salamander) in pools of a Kentucky stream, found that females preferred pools without predatory Lepomis cyanellus (Green Sunfish), and that the number of egg masses present in a pool historically containing fish increased significantly the year after fish had been extirpated from the pool. Palen et al. (2005) determined that Ambystoma gracile (Northwestern Salamander) and Ambystoma macrodactylum (Longtoed Salamander) eggs were deposited either at increased depth or in full shaded habitats, respectively, as water transperancy to UV-B radiation increased.

cis Retinol oxidation regulates photoreceptor access to the retina visual cycle and cone pigment regeneration

PubMed Central

Sato, Shinya

2016-01-01

Key points This study explores the nature of the cis retinol that Müller cells in the retina provide to cones for the regeneration of their visual pigment.We report that the retina visual cycle provides cones exclusively with 11‐cis chromophore in both salamander and mouse and show that this selectivity is dependent on the 11‐cis‐specific cellular retinaldehyde binding protein (CRALBP) present in Müller cells.Even though salamander blue cones and green rods share the same visual pigment, only blue cones but not green rods are able to dark‐adapt in the retina following a bleach and to use exogenous 9‐cis retinol for pigment regeneration, suggesting that access to the retina visual cycle is cone‐specific and pigment‐independent.Our results show that the retina produces 11‐cis retinol that can be oxidized and used for pigment regeneration and dark adaptation selectively in cones and not in rods. Abstract Chromophore supply by the retinal Müller cells (retina visual cycle) supports the efficient pigment regeneration required for cone photoreceptor function in bright light. Surprisingly, a large fraction of the chromophore produced by dihydroceramide desaturase‐1, the putative all‐trans retinol isomerase in Müller cells, appears to be 9‐cis retinol. In contrast, the canonical retinal pigment epithelium (RPE) visual cycle produces exclusively 11‐cis retinal. Here, we used the different absorption spectra of 9‐cis and 11‐cis pigments to identify the isoform of the chromophore produced by the visual cycle of the intact retina. We found that the spectral sensitivity of salamander and mouse cones dark‐adapted in the isolated retina (with only the retina visual cycle) was similar to that of cones dark‐adapted in the intact eye (with both the RPE and retina visual cycles) and consistent with pure 11‐cis pigment composition. However, in mice lacking the cellular retinaldehyde binding protein (CRALBP), cone spectral sensitivity contained a

Low Vision Rehabilitation of Retinitis Pigmentosa. Practice Report

ERIC Educational Resources Information Center

Rundquist, John

2004-01-01

Retinitis pigmentosa is a rod-cone dystrophy, commonly genetic in nature. Approximately 60-80% of those with retinitis pigmentosa inherit it by an autosomal recessive transmission (Brilliant, 1999). There have been some reported cases with no known family history. The symptoms of retinitis pigmentosa are decreased acuity, photophobia, night…

RPGR-Associated Retinal Degeneration in Human X-Linked RP and a Murine Model

PubMed Central

Huang, Wei Chieh; Wright, Alan F.; Roman, Alejandro J.; Cideciyan, Artur V.; Manson, Forbes D.; Gewaily, Dina Y.; Schwartz, Sharon B.; Sadigh, Sam; Limberis, Maria P.; Bell, Peter; Wilson, James M.; Swaroop, Anand; Jacobson, Samuel G.

2012-01-01

Purpose. We investigated the retinal disease due to mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in human patients and in an Rpgr conditional knockout (cko) mouse model. Methods. XLRP patients with RPGR-ORF15 mutations (n = 35, ages at first visit 5–72 years) had clinical examinations, and rod and cone perimetry. Rpgr-cko mice, in which the proximal promoter and first exon were deleted ubiquitously, were back-crossed onto a BALB/c background, and studied with optical coherence tomography and electroretinography (ERG). Retinal histopathology was performed on a subset. Results. Different patterns of rod and cone dysfunction were present in patients. Frequently, there were midperipheral losses with residual rod and cone function in central and peripheral retina. Longitudinal data indicated that central rod loss preceded peripheral rod losses. Central cone-only vision with no peripheral function was a late stage. Less commonly, patients had central rod and cone dysfunction, but preserved, albeit abnormal, midperipheral rod and cone vision. Rpgr-cko mice had progressive retinal degeneration detectable in the first months of life. ERGs indicated relatively equal rod and cone disease. At late stages, there was greater inferior versus superior retinal degeneration. Conclusions. RPGR mutations lead to progressive loss of rod and cone vision, but show different patterns of residual photoreceptor disease expression. Knowledge of the patterns should guide treatment strategies. Rpgr-cko mice had onset of degeneration at relatively young ages and progressive photoreceptor disease. The natural history in this model will permit preclinical proof-of-concept studies to be designed and such studies should advance progress toward human therapy. PMID:22807293

Gene replacement therapy for retinal CNG channelopathies.

PubMed

Schön, Christian; Biel, Martin; Michalakis, Stylianos

2013-10-01

Visual phototransduction relies on the function of cyclic nucleotide-gated channels in the rod and cone photoreceptor outer segment plasma membranes. The role of these ion channels is to translate light-triggered changes in the second messenger cyclic guanosine 3'-5'-monophosphate levels into an electrical signal that is further processed within the retinal network and then sent to higher visual centers. Rod and cone photoreceptors express distinct CNG channels. The rod photoreceptor CNG channel is composed of one CNGB1 and three CNGA1 subunits, whereas the cone channel is formed by one CNGB3 and three CNGA3 subunits. Mutations in any of these channel subunits result in severe and currently untreatable retinal degenerative diseases like retinitis pigmentosa or achromatopsia. In this review, we provide an overview of the human diseases and relevant animal models of CNG channelopathies. Furthermore, we summarize recent results from preclinical gene therapy studies using adeno-associated viral vectors and discuss the efficacy and translational potential of these gene therapeutic approaches.

Refinement of the cone-rod retinal dystrophy locus on chromosome 19q

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gregory, C.Y.; Evans, K.; Bhattacharya, S.S.

1994-11-01

Cone-rod dystrophy (CRD) is a severe example of an inherited retinal dystrophy: ophthalmic diseases that as a group constitute the commonest causes of blindness in children in the developed world and account for a significant proportion of visual handicap in adults. Two case reports suggested loci for CRD-causing genes on chromosomes 18q and chromosome 17q. Recently, we reported the results of a total genome search that localized an autosomal dominant form of CRD to chromosome 19q in the region 19q13.1-q13.2. Since then, using data from a short tandem repeat-polymorphism linkage map of chromosome 19 and recently developed microsatellite markers inmore » this region, we have been able to further refine the localization of the chromosome 19q CRD-causing gene. Seven new microsatellite markers were used to genotype 34 affected subjects, 22 unaffected subjects, and 15 spouses. Two-point, multipoint, and FASTMAP analyses were performed. 11 refs., 1 tab.« less

Conservation assessment for the Siskiyou Mountains salamander and Scott Bar salamander in northern California.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vinikour, W. S.; LaGory, K. E.; Adduci, J. J.

2006-10-20

The purpose of this conservation assessment is to summarize existing knowledge regarding the biology and ecology of the Siskiyou Mountains salamander and Scott Bar salamander, identify threats to the two species, and identify conservation considerations to aid federal management for persistence of the species. The conservation assessment will serve as the basis for a conservation strategy for the species.

Effects of timber harvests and silvicultural edges on terrestrial salamanders.

PubMed

MacNeil, Jami E; Williams, Rod N

2014-01-01

Balancing timber production and conservation in forest management requires an understanding of how timber harvests affect wildlife species. Terrestrial salamanders are useful indicators of mature forest ecosystem health due to their importance to ecosystem processes and sensitivity to environmental change. However, the effects of timber harvests on salamanders, though often researched, are still not well understood. To further this understanding, we used artificial cover objects to monitor the relative abundance of terrestrial salamanders for two seasons (fall and spring) pre-harvest and five seasons post-harvest in six forest management treatments, and for three seasons post-harvest across the edge gradients of six recent clearcuts. In total, we recorded 19,048 encounters representing nine species of salamanders. We observed declines in mean encounters of eastern red-backed salamanders (Plethodon cinereus) and northern slimy salamanders (P. glutinosus) from pre- to post-harvest in group selection cuts and in clearcuts. However, we found no evidence of salamander declines at shelterwoods and forested sites adjacent to harvests. Edge effects induced by recent clearcuts influenced salamanders for approximately 20 m into the forest, but edge influence varied by slope orientation. Temperature, soil moisture, and canopy cover were all correlated with salamander counts. Our results suggest silvicultural techniques that remove the forest canopy negatively affect salamander relative abundance on the local scale during the years immediately following harvest, and that the depth of edge influence of clearcuts on terrestrial salamanders is relatively shallow (<20 m). Small harvests (<4 ha) and techniques that leave the forest canopy intact may be compatible with maintaining terrestrial salamander populations across a forested landscape. Our results demonstrate the importance of examining species-specific responses and monitoring salamanders across multiple seasons and years

Effects of Timber Harvests and Silvicultural Edges on Terrestrial Salamanders

PubMed Central

MacNeil, Jami E.; Williams, Rod N.

2014-01-01

Balancing timber production and conservation in forest management requires an understanding of how timber harvests affect wildlife species. Terrestrial salamanders are useful indicators of mature forest ecosystem health due to their importance to ecosystem processes and sensitivity to environmental change. However, the effects of timber harvests on salamanders, though often researched, are still not well understood. To further this understanding, we used artificial cover objects to monitor the relative abundance of terrestrial salamanders for two seasons (fall and spring) pre-harvest and five seasons post-harvest in six forest management treatments, and for three seasons post-harvest across the edge gradients of six recent clearcuts. In total, we recorded 19,048 encounters representing nine species of salamanders. We observed declines in mean encounters of eastern red-backed salamanders (Plethodon cinereus) and northern slimy salamanders (P. glutinosus) from pre- to post-harvest in group selection cuts and in clearcuts. However, we found no evidence of salamander declines at shelterwoods and forested sites adjacent to harvests. Edge effects induced by recent clearcuts influenced salamanders for approximately 20 m into the forest, but edge influence varied by slope orientation. Temperature, soil moisture, and canopy cover were all correlated with salamander counts. Our results suggest silvicultural techniques that remove the forest canopy negatively affect salamander relative abundance on the local scale during the years immediately following harvest, and that the depth of edge influence of clearcuts on terrestrial salamanders is relatively shallow (<20 m). Small harvests (<4 ha) and techniques that leave the forest canopy intact may be compatible with maintaining terrestrial salamander populations across a forested landscape. Our results demonstrate the importance of examining species-specific responses and monitoring salamanders across multiple seasons and years

Adaptation to changes in higher-order stimulus statistics in the salamander retina.

PubMed

Tkačik, Gašper; Ghosh, Anandamohan; Schneidman, Elad; Segev, Ronen

2014-01-01

Adaptation in the retina is thought to optimize the encoding of natural light signals into sequences of spikes sent to the brain. While adaptive changes in retinal processing to the variations of the mean luminance level and second-order stimulus statistics have been documented before, no such measurements have been performed when higher-order moments of the light distribution change. We therefore measured the ganglion cell responses in the tiger salamander retina to controlled changes in the second (contrast), third (skew) and fourth (kurtosis) moments of the light intensity distribution of spatially uniform temporally independent stimuli. The skew and kurtosis of the stimuli were chosen to cover the range observed in natural scenes. We quantified adaptation in ganglion cells by studying linear-nonlinear models that capture well the retinal encoding properties across all stimuli. We found that the encoding properties of retinal ganglion cells change only marginally when higher-order statistics change, compared to the changes observed in response to the variation in contrast. By analyzing optimal coding in LN-type models, we showed that neurons can maintain a high information rate without large dynamic adaptation to changes in skew or kurtosis. This is because, for uncorrelated stimuli, spatio-temporal summation within the receptive field averages away non-gaussian aspects of the light intensity distribution.

Stream salamanders as indicators of stream quality in Maryland, USA

USGS Publications Warehouse

Southerland, M.T.; Jung, R.E.; Baxter, D.P.; Chellman, I.C.; Mercurio, G.; Volstad, J.H.

2004-01-01

Biological indicators are critical to the protection of small, headwater streams and the ecological values they provide. Maryland and other state monitoring programs have determined that fish indicators are ineffective in small streams, where stream salamanders may replace fish as top predators. Because of their life history, physiology, abundance, and ubiquity, stream salamanders are likely representative of biological integrity in these streams. The goal of this study was to determine whether stream salamanders are effective indicators of ecological conditions across biogeographic regions and gradients of human disturbance. During the summers of 2001 and 2002, we intensively surveyed for stream salamanders at 76 stream sites located west of the Maryland Coastal Plain, sites also monitored by the Maryland Biological Stream Survey (MBSS) and City of Gaithersburg. We found 1,584 stream salamanders, including all eight species known in Maryland, using two 15 ? 2 m transects and two 4 m2 quadrats that spanned both stream bank and channel. We performed removal sampling on transects to estimate salamander species detection probabilities, which ranged from 0.67-0.85. Stepwise regressions identified 15 of 52 non-salamander variables, representing water quality, physical habitat, land use, and biological conditions, which best predicted salamander metrics. Indicator development involved (1) identifying reference (non-degraded) and degraded sites (using percent forest, shading, riparian buffer width, aesthetic rating, and benthic macroinvertebrate and fish indices of biotic integrity); (2) testing 12 candidate salamander metrics (representing species richness and composition, abundance, species tolerance, and reproductive function) for their ability to distinguish reference from degraded sites; and (3) combining metrics into an index that effectively discriminated sites according to known stream conditions. Final indices for Highlands, Piedmont, and Non-Coastal Plain

Reproductive biology of Ambystoma salamanders in the southeastern United States

USGS Publications Warehouse

Glorioso, Brad M.; Waddle, J. Hardin; Hefner, J. M.

2015-01-01

Reproductive aspects of Ambystoma salamanders were investigated at sites in Louisiana (2010–12) and Mississippi (2013). Three species occurred at the Louisiana site, Spotted Salamander (A. maculatum), Marbled Salamander (A. opacum), and Mole Salamander (A. talpoideum), whereas only Spotted Salamanders were studied at the Mississippi site. A total of 162 and 71 egg masses of Spotted Salamanders were examined at the Louisiana and Mississippi sites, respectively. Significantly more Spotted Salamander eggs per egg mass were observed at the Mississippi site (x̄ = 78.2) than the Louisiana site (x̄ = 53.8; P < 0.001). The mean snout–vent length of female Spotted Salamanders at the Mississippi site (82.9 mm) was significantly larger than the Louisiana site (76.1 mm; P < 0.001). Opaque Spotted Salamander egg masses were not found at the Mississippi site, but accounted for 11% of examined egg masses at the Louisiana site. The mean number of eggs per egg mass at the Louisiana site did not differ between opaque (47.3) and clear (54.6) egg masses (P = 0.21). A total of 47 egg masses of the Mole Salamander were examined, with a mean number of 6.7 embryos per mass. Twenty-three individual nests of the Marbled Salamander were found either under or in decaying logs in the dry pond basins. There was no difference between the mean numbers of eggs per mass of attended nests (93.0) versus those that were discovered unattended (86.6; P = 0.67). Females tended to place their nests at intermediate heights within the pond basin.

Vertebrate rod photoreceptors express both BK and IK calcium-activated potassium channels, but only BK channels are involved in receptor potential regulation.

PubMed

Pelucchi, Bruna; Grimaldi, Annalisa; Moriondo, Andrea

2008-01-01

In salamander rods, Ca(2+)-activated K(+) current (I(KCa)) provides an effective "clamp" of the dark membrane potential to its normal resting level. By a combination of electrophysiological, pharmacological, and immunohistochemical approaches, we show that salamander rods functionally express large-conductance Ca(2+)- and voltage-dependent potassium (BK) channel and intermediate-conductance Ca(2+)-dependent potassium (IK) channel, but not small-conductance Ca(2+)-dependent potassium channel (SK) subtypes. Application of 100 nM iberiotoxin and 100 nM clotrimazole reduced net I(KCa) to 36% and 63%, respectively, whereas the current was unaffected by application of 1 microM apamin. Consistently, anti- SK1, -SK2, and -SK3 antibodies were unable to stain rod photoreceptors, whereas both anti-BK and -SK4/ IK1 antibodies heavily stained the ellipsoid region of the inner segments of the rods. Moreover, by using current-clamp experiments, it was clearly seen that the strong clamping effect of the total I(KCa) was lost when IbTx, but not CLTZ, was applied to the bath. This behavior strongly suggests that of BK and IK channels, only the former are responsible for the clamping effect on the photoreceptor membrane potential.

Evolution of Gigantism in Amphiumid Salamanders

PubMed Central

Bonett, Ronald M.; Chippindale, Paul T.; Moler, Paul E.; Van Devender, R. Wayne; Wake, David B.

2009-01-01

The Amphiumidae contains three species of elongate, permanently aquatic salamanders with four diminutive limbs that append one, two, or three toes. Two of the species, Amphiuma means and A. tridactylum, are among the largest salamanders in the world, reaching lengths of more than one meter, whereas the third species (A. pholeter), extinct amphiumids, and closely related salamander families are relatively small. Amphiuma means and A. tridactylum are widespread species and live in a wide range of lowland aquatic habitats on the Coastal Plain of the southeastern United States, whereas A. pholeter is restricted to very specialized organic muck habitats and is syntopic with A. means. Here we present analyses of sequences of mitochondrial and nuclear loci from across the distribution of the three taxa to assess lineage diversity, relationships, and relative timing of divergence in amphiumid salamanders. In addition we analyze the evolution of gigantism in the clade. Our analyses indicate three lineages that have diverged since the late Miocene, that correspond to the three currently recognized species, but the two gigantic species are not each other's closest relatives. Given that the most closely related salamander families and fossil amphiumids from the Upper Cretaceous and Paleocene are relatively small, our results suggest at least two extreme changes in body size within the Amphuimidae. Gigantic body size either evolved once as the ancestral condition of modern amphiumas, with a subsequent strong size reduction in A. pholeter, or gigantism independently evolved twice in the modern species, A. means and A. tridactylum. These patterns are concordant with differences in habitat breadth and range size among lineages, and have implications for reproductive isolation and diversification of amphiumid salamanders. PMID:19461997

Terrestrial salamander abundance on reclaimed mountaintop removal mines

USGS Publications Warehouse

Wood, Petra Bohall; Williams, Jennifer M.

2013-01-01

Mountaintop removal mining, a large-scale disturbance affecting vegetation, soil structure, and topography, converts landscapes from mature forests to extensive grassland and shrubland habitats. We sampled salamanders using drift-fence arrays and coverboard transects on and near mountaintop removal mines in southern West Virginia, USA, during 2000–2002. We compared terrestrial salamander relative abundance and species richness of un-mined, intact forest with habitats on reclaimed mountaintop removal mines (reclaimed grassland, reclaimed shrubland, and fragmented forest). Salamanders within forests increased in relative abundance with increasing distance from reclaimed mine edge. Reclaimed grassland and shrubland habitats had lower relative abundance and species richness than forests. Characteristics of reclaimed habitats that likely contributed to lower salamander abundance included poor soils (dry, compacted, little organic matter, high rock content), reduced vertical structure of vegetation and little tree cover, and low litter and woody debris cover. Past research has shown that salamander populations reduced by clearcutting may rebound in 15–24 years. Time since disturbance was 7–28 years in reclaimed habitats on our study areas and salamander populations had not reached levels found in adjacent mature forests.

Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision.

PubMed

Beier, Corinne; Hovhannisyan, Anahit; Weiser, Sydney; Kung, Jennifer; Lee, Seungjun; Lee, Dae Yeong; Huie, Philip; Dalal, Roopa; Palanker, Daniel; Sher, Alexander

2017-04-26

Upon degeneration of photoreceptors in the adult retina, interneurons, including bipolar cells, exhibit a plastic response leading to their aberrant rewiring. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of deafferented bipolar cells to establish functional synapses with photoreceptors is poorly understood. Here we use photocoagulation to selectively destroy photoreceptors in adult rabbits while preserving the inner retina. We find that rods and cones shift into the ablation zone over several weeks, reducing the blind spot at scotopic and photopic luminances. During recovery, rod and cone bipolar cells exhibit markedly different responses to deafferentation. Rod bipolar cells extend their dendrites to form new synapses with healthy photoreceptors outside the lesion, thereby restoring visual function in the deafferented retina. Secretagogin-positive cone bipolar cells did not exhibit such obvious dendritic restructuring. These findings are encouraging to the idea of photoreceptor reintroduction for vision restoration in patients blinded by retinal degeneration. At the same time, they draw attention to the postsynaptic side of photoreceptor reintroduction; various bipolar cell types, representing different visual pathways, vary in their response to the photoreceptor loss and in their consequent dendritic restructuring. SIGNIFICANCE STATEMENT Loss of photoreceptors during retinal degeneration results in permanent visual impairment. Strategies for vision restoration based on the reintroduction of photoreceptors inherently rely on the ability of the remaining retinal neurons to correctly synapse with new photoreceptors. We show that deafferented bipolar cells in the adult mammalian retina can reconnect to rods and cones and restore retinal sensitivity at scotopic and photopic luminances. Rod bipolar cells extend their dendrites to form new synapses with healthy rod photoreceptors. These findings support

Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision

PubMed Central

Hovhannisyan, Anahit; Kung, Jennifer; Lee, Seungjun; Lee, Dae Yeong; Huie, Philip; Dalal, Roopa; Palanker, Daniel

2017-01-01

Upon degeneration of photoreceptors in the adult retina, interneurons, including bipolar cells, exhibit a plastic response leading to their aberrant rewiring. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of deafferented bipolar cells to establish functional synapses with photoreceptors is poorly understood. Here we use photocoagulation to selectively destroy photoreceptors in adult rabbits while preserving the inner retina. We find that rods and cones shift into the ablation zone over several weeks, reducing the blind spot at scotopic and photopic luminances. During recovery, rod and cone bipolar cells exhibit markedly different responses to deafferentation. Rod bipolar cells extend their dendrites to form new synapses with healthy photoreceptors outside the lesion, thereby restoring visual function in the deafferented retina. Secretagogin-positive cone bipolar cells did not exhibit such obvious dendritic restructuring. These findings are encouraging to the idea of photoreceptor reintroduction for vision restoration in patients blinded by retinal degeneration. At the same time, they draw attention to the postsynaptic side of photoreceptor reintroduction; various bipolar cell types, representing different visual pathways, vary in their response to the photoreceptor loss and in their consequent dendritic restructuring. SIGNIFICANCE STATEMENT Loss of photoreceptors during retinal degeneration results in permanent visual impairment. Strategies for vision restoration based on the reintroduction of photoreceptors inherently rely on the ability of the remaining retinal neurons to correctly synapse with new photoreceptors. We show that deafferented bipolar cells in the adult mammalian retina can reconnect to rods and cones and restore retinal sensitivity at scotopic and photopic luminances. Rod bipolar cells extend their dendrites to form new synapses with healthy rod photoreceptors. These findings support

Salamander occupancy in headwater stream networks

USGS Publications Warehouse

Grant, E.H.C.; Green, L.E.; Lowe, W.H.

2009-01-01

1. Stream ecosystems exhibit a highly consistent dendritic geometry in which linear habitat units intersect to create a hierarchical network of connected branches. 2. Ecological and life history traits of species living in streams, such as the potential for overland movement, may interact with this architecture to shape patterns of occupancy and response to disturbance. Specifically, large-scale habitat alteration that fragments stream networks and reduces connectivity may reduce the probability a stream is occupied by sensitive species, such as stream salamanders. 3. We collected habitat occupancy data on four species of stream salamanders in first-order (i.e. headwater) streams in undeveloped and urbanised regions of the eastern U.S.A. We then used an information-theoretic approach to test alternative models of salamander occupancy based on a priori predictions of the effects of network configuration, region and salamander life history. 4. Across all four species, we found that streams connected to other first-order streams had higher occupancy than those flowing directly into larger streams and rivers. For three of the four species, occupancy was lower in the urbanised region than in the undeveloped region. 5. These results demonstrate that the spatial configuration of stream networks within protected areas affects the occurrences of stream salamander species. We strongly encourage preservation of network connections between first-order streams in conservation planning and management decisions that may affect stream species.

HIF-1α stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa.

PubMed

Olivares-González, Lorena; Martínez-Fernández de la Cámara, Cristina; Hervás, David; Millán, José María; Rodrigo, Regina

2018-05-01

Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive and irreversible loss of vision due to rod and cone degeneration. Evidence suggests that an inappropriate oxygen level could contribute to its pathogenesis. Rod cell death could increase oxygen concentration, reduce hypoxia-inducible factor 1 (HIF-1α) and contribute to cone cell death. The purposes of this study were: 1) to analyze the temporal profile of HIF-1α, its downstream effectors VEGF, endothelin-1 (ET-1), iNOS, and glucose transporter 1 (GLUT1), and neuroinflammation in retinas of the murine model of rd10 ( retinal degeneration 10) mice with RP; 2) to study oxygen bioavailability in these retinas; and 3) to investigate how stabilizing HIF-1α proteins with dimethyloxaloglycine (DMOG), a prolyl hydroxylase inhibitor, affects retinal degeneration, neuroinflammation, and antioxidant response in rd10 mice. A generalized down-regulation of HIF-1α and its downstream targets was detected in parallel with reactive gliosis, suggesting high oxygen levels during retinal degeneration. At postnatal d 18, DMOG treatment reduced photoreceptor cell death and glial activation. In summary, retinas of rd10 mice seem to be exposed to a hyperoxic environment even at early stages of degeneration. HIF-1α stabilization could have a temporal neuroprotective effect on photoreceptor cell survival, glial activation, and antioxidant response at early stages of RP.-Olivares-González, L., Martínez-Fernández de la Cámara, C., Hervás, D., Millán, J. M., Rodrigo, R. HIF-1α stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa.

Retinitis pigmentosa, pigmentary retinopathies, and neurologic diseases.

PubMed

Bhatti, M Tariq

2006-09-01

Retinitis pigmentosa (RP) refers to a group of inherited retinal diseases with phenotypic and genetic heterogeneity. The pathophysiologic basis of the progressive visual loss in patients with RP is not completely understood but is felt to be due to a primary retinal photoreceptor cell degenerative process mainly affecting the rods of the peripheral retina. In most cases RP is seen in isolation (nonsyndromic), but in some other cases it may be a part of a genetic, metabolic, or neurologic syndrome or disorder. Nyctalopia, or night blindness, is the most common symptom of RP. The classic fundus appearance of RP includes retinal pigment epithelial cell changes resulting in retinal hypo- or hyperpigmentation ("salt-and-pepper"), retinal granularity, and bone spicule formation. The retinal vessels are often narrowed or attenuated and there is a waxy pallor appearance of the optic nerve head. Electroretinography will demonstrate rod and cone photoreceptor cell dysfunction and is a helpful test in the diagnosis and monitoring of patients with RP. A detailed history with pedigree analysis, a complete ocular examination, and the appropriate paraclinical testing should be performed in patients complaining of visual difficulties at night or in dim light. This review discusses the clinical manifestations of RP as well as describing the various systemic diseases, with a special emphasis on neurologic diseases, associated with a pigmentary retinopathy.

Experimental infection of native north Carolina salamanders with Batrachochytrium dendrobatidis.

PubMed

Chinnadurai, Sathya K; Cooper, David; Dombrowski, Daniel S; Poore, Matthew F; Levy, Michael G

2009-07-01

Chytridiomycosis is an often fatal fungal disease of amphibians caused by Batrachochytrium dendrobatidis. This disease has been implicated in the worldwide decline of many anuran species, but studies of chytridiomycosis in wild salamanders are limited. Between August 2006 and December 2006, we tested wild amphibians in North Carolina, USA (n=212) by polymerase chain reaction (PCR). We identified three PCR-positive animals: one Rana clamitans and two Plethodontid salamanders. We experimentally infected two species of native North Carolina Plethodontid salamanders, the slimy salamander (Plethodon glutinosus) and the Blue Ridge Mountain dusky salamander (Desmognathus orestes) with 1,000,000 zoospores of B. dendrobatidis per animal. Susceptibility was species dependent; all slimy salamanders developed clinical signs of chytridiomycosis, and one died, whereas dusky salamanders remained unaffected. In a second experiment, we challenged naïve slimy salamanders with either 10,000 or 100,000 motile zoospores per animal. Clinical signs consistent with chytridiomycosis were not observed at either dose or in uninfected controls during the 45 days of this experiment. All animals inoculated with B. dendrobatidis in both experiments, regardless of dose, tested positive by PCR. Our study indicates that slimy salamanders are more susceptible to clinical chytridiomycosis than dusky salamanders, and in a laboratory setting, a dose greater than 100,000 zoospores per animal is required to induce clinical disease. This study also indicates that PCR is a very sensitive tool for detecting B. dendrobatidis infection, even in animals that are clinically unaffected, thus positive results should be interpreted with caution.

Progress toward the maintenance and repair of degenerating retinal circuitry.

PubMed

Vugler, Anthony A

2010-01-01

Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

ApoER2 Function in the Establishment and Maintenance of Retinal Synaptic Connectivity

PubMed Central

Trotter, Justin H.; Klein, Martin; Jinwal, Umesh K.; Abisambra, Jose F.; Dickey, Chad A.; Tharkur, Jeremy; Masiulis, Irene; Ding, Jindong; Locke, Kirstin G.; Rickman, Catherine Bowes; Birch, David G.; Weeber, Edwin J.; Herz, Joachim

2011-01-01

The cellular and molecular mechanisms responsible for the development of inner retinal circuitry are poorly understood. Reelin and apolipoprotein E (apoE), ligands of apoE receptor 2 (ApoER2), are involved in retinal development and degeneration, respectively. Here we describe the function of ApoER2 in the developing and adult retina. ApoER2 expression was highest during postnatal inner retinal synaptic development and was considerably lower in the mature retina. Both during development and in the adult ApoER2 was expressed by A-II amacrine cells. ApoER2 knockout (KO) mice had rod bipolar morphogenic defects, altered A-II amacrine dendritic development, and impaired rod-driven retinal responses. The presence of an intact ApoER2 NPxY motif, necessary for binding disabled-1 (Dab1) and transducing the Reelin signal, was also necessary for development of the rod bipolar pathway while the alternatively-spliced exon19 was not. Mice deficient in another Reelin receptor, very low-density lipoprotein receptor (VLDLR), had normal rod bipolar morphology but altered A-II amacrine dendritic development. VLDLR KO mice also had reductions in oscillatory potentials and delayed synaptic response intervals. Interestingly, age-related reductions in rod and cone function were observed in both ApoER2 and VLDLR KOs. These results support a pivotal role for ApoER2 in the establishment and maintenance of normal retinal synaptic connectivity. PMID:21976526

Unilateral retinitis pigmentosa sine pigmento.

PubMed

Pearlman, J T; Saxton, J; Hoffman, G

1976-05-01

A patient presented with unilateral findings of night blindness shown by impaired rod function and dark adaptation, constricted visual fields with good central acuity, a barely recordable electro-retinographic b-wave, and a unilaterally impaired electro-oculogram. There were none of the pigmentary changes usually associated with retinitis pigmentosa. The unaffected right eye was normal in all respects. Therefore the case is most probably one of unilateral retinitis pigmentosa sine pigmento.

Cone rod dystrophies

PubMed Central

Hamel, Christian P

2007-01-01

Cone rod dystrophies (CRDs) (prevalence 1/40,000) are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP), also called the rod cone dystrophies (RCDs) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7). Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far). The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs), CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs), and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs). It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is always advised. Currently

Unilateral retinitis pigmentosa sine pigmento.

PubMed Central

Pearlman, J T; Saxton, J; Hoffman, G

1976-01-01

A patient presented with unilateral findings of night blindness shown by impaired rod function and dark adaptation, constricted visual fields with good central acuity, a barely recordable electro-retinographic b-wave, and a unilaterally impaired electro-oculogram. There were none of the pigmentary changes usually associated with retinitis pigmentosa. The unaffected right eye was normal in all respects. Therefore the case is most probably one of unilateral retinitis pigmentosa sine pigmento. Images PMID:952804

Homing orientation in salamanders: A mechanism involving chemical cues

NASA Technical Reports Server (NTRS)

Madison, D. M.

1972-01-01

A detailed description is given of experiments made to determine the senses and chemical cues used by salamanders for homing orientation. Sensory impairment and cue manipulative techniques were used in the investigation. All experiments were carried out at night. Results show that sense impaired animals did not home as readily as those who were blind but retained their sensory mechanism. This fact suggests that the olfactory mechanism is necessary for homing in the salamander. It was determined that after the impaired salamander regenerated its sensory mechanism it too returned home. It was concluded that homing ability in salamanders is direction independent, distant dependent, and vision independent.

EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression

PubMed Central

McGuigan, David B.; Heon, Elise; Cideciyan, Artur V.; Ratnapriya, Rinki; Lu, Monica; Sumaroka, Alexander; Roman, Alejandro J.; Batmanabane, Vaishnavi; Garafalo, Alexandra V.; Stone, Edwin M.; Jacobson, Samuel G.

2017-01-01

Mutations in the EYS (eyes shut homolog) gene are a common cause of autosomal recessive (ar) retinitis pigmentosa (RP). Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT), and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit), some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK. PMID:28704921

Variation in sensitivity, absorption and density of the central rod distribution with eccentricity.

PubMed

Tornow, R P; Stilling, R

1998-01-01

To assess the human rod photopigment distribution and sensitivity with high spatial resolution within the central +/-15 degrees and to compare the results of pigment absorption, sensitivity and rod density distribution (number of rods per square degree). Rod photopigment density distribution was measured with imaging densitometry using a modified Rodenstock scanning laser ophthalmoscope. Dark-adapted sensitivity profiles were measured with green stimuli (17' arc diameter, 1 degrees spacing) using a T ubingen manual perimeter. Sensitivity profiles were plotted on a linear scale and rod photopigment optical density distribution profiles were converted to absorption profiles of the rod photopigment layer. Both the absorption profile of the rod photopigment and the linear sensitivity profile for green stimuli show a minimum at the foveal center and increase steeply with eccentricity. The variation with eccentricity corresponds to the rod density distribution. Rod photopigment absorption profiles, retinal sensitivity profiles, and the rod density distribution are linearly related within the central +/-15 degrees. This is in agreement with theoretical considerations. Both methods, imaging retinal densitometry using a scanning laser ophthalmoscope and dark-adapted perimetry with small green stimuli, are useful for assessing the central rod distribution and sensitivity. However, at present, both methods have limitations. Suggestions for improving the reliability of both methods are given.

Bromeliad Selection by Two Salamander Species in a Harsh Environment

PubMed Central

Ruano-Fajardo, Gustavo; Rovito, Sean M.; Ladle, Richard J.

2014-01-01

Bromeliad phytotelmata are frequently used by several Neotropical amphibian taxa, possibly due to their high humidity, microclimatic stability, and role as a refuge from predators. Indeed, the ability of phytotelmata to buffer against adverse environmental conditions may be instrumental in allowing some amphibian species to survive during periods of environmental change or to colonize sub-optimal habitats. Association between bromeliad traits and salamanders has not been studied at a fine scale, despite the intimate association of many salamander species with bromeliads. Here, we identify microhabitat characteristics of epiphytic bromeliads used by two species of the Bolitoglossa morio group (B. morio and B. pacaya) in forest disturbed by volcanic activity in Guatemala. Specifically, we measured multiple variables for bromeliads (height and position in tree, phytotelma water temperature and pH, canopy cover, phytotelma size, leaf size, and tree diameter at breast height), as well as salamander size. We employed a DNA barcoding approach to identify salamanders. We found that B. morio and B. pacaya occurred in microsympatry in bromeliads and that phytotelmata size and temperature of bromeliad microhabitat were the most important factors associated with the presence of salamanders. Moreover, phytotelmata with higher pH contained larger salamanders, suggesting that larger salamanders or aggregated individuals might modify pH. These results show that bromeliad selection is nonrandom with respect to microhabitat characteristics, and provide insight into the relationship between salamanders and this unique arboreal environment. PMID:24892414

Cone and Rod Loss in Stargardt Disease Revealed by Adaptive Optics Scanning Light Ophthalmoscopy

PubMed Central

Song, Hongxin; Rossi, Ethan A.; Latchney, Lisa; Bessette, Angela; Stone, Edwin; Hunter, Jennifer J.; Williams, David R.; Chung, Mina

2015-01-01

Importance Stargardt disease (STGD1) is characterized by macular atrophy and flecks in the retinal pigment epithelium. The causative ABCA4 gene encodes a protein localizing to photoreceptor outer segments. The pathologic steps by which ABCA4 mutations lead to clinically detectable retinal pigment epithelium changes remain unclear. We investigated early STGD1 using adaptive optics scanning light ophthalmoscopy. Observations Adaptive optics scanning light ophthalmoscopy imaging of 2 brothers with early STGD1 and their unaffected parents was compared with conventional imaging. Cone and rod spacing were increased in both patients (P <.001) with a dark cone appearance. No foveal cones were detected in the older brother. In the younger brother, foveal cones were enlarged with low density (peak cone density, 48.3 × 103 cones/mm2). The ratio of cone to rod spacing was increased in both patients, with greater divergence from normal approaching the foveal center, indicating that cone loss predominates centrally and rod loss increases peripherally. Both parents had normal photoreceptor mosaics. Genetic testing revealed 3 disease-causing mutations. Conclusions and Relevance This study provides in vivo images of rods and cones in STGD1. Although the primary clinical features of STGD1 are retinal pigment epithelial lesions, adaptive optics scanning light ophthalmoscopy reveals increased cone and rod spacing in areas that appear normal in conventional images, suggesting that photoreceptor loss precedes clinically detectable retinal pigment epithelial disease in STGD1. PMID:26247787

Impact of valley fills on streamside salamanders in southern West Virginia

USGS Publications Warehouse

Wood, Petra Bohall; Williams, Jennifer M.

2013-01-01

Valley fills associated with mountaintop-removal mining bury stream headwaters and affect water quality and ecological function of reaches below fills. We quantified relative abundance of streamside salamanders in southern West Virginia during 2002 in three streams below valley fills (VFS) and in three reference streams (RS). We surveyed 36 10- × 2-m stream transects, once in summer and fall, paired by order and structure. Of 2,343 salamanders captured, 66.7% were from RS. Total salamanders (adults plus larvae) were more abundant in RS than VFS for first-order and second-order reaches. Adult salamanders had greater abundance in first-order reaches of RS than VFS. Larval salamanders were more abundant in second-order reaches of RS than VFS. No stream width or mesohabitat variables differed between VFS and RS. Only two cover variables differed. Silt cover, greater in VFS than RS first-order reaches, is a likely contributor to reduced abundance of salamanders in VFS. Second-order RS had more boulder cover than second-order VFS, which may have contributed to the higher total and larval salamander abundance in RS. Water chemistry assessments of our VFS and RS reported elevated levels of metal and ion concentrations in VFS, which can depress macroinvertebrate populations and likely affect salamander abundance. Valley fills appear to have significant negative effects on stream salamander abundance due to alterations in habitat structure, water quality and chemistry, and macroinvertebrate communities in streams below fills.

Retinitis pigmentosa.

PubMed

Hamel, Christian

2006-10-11

Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms). Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis).

Retinitis pigmentosa

PubMed Central

Hamel, Christian

2006-01-01

Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms). Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis). PMID:17032466

RECOVERY OF ROD PHOTORESPONSES IN ABCR-DEFICIENT MICE

PubMed Central

Pawar, Ambarish S.; Qtaishat, Nasser M.; Little, Deborah M.; Pepperberg, David R.

2010-01-01

Purpose ABCR protein in the rod outer segment is thought to facilitate movement of the all-trans retinal photoproduct of rhodopsin bleaching out of the disk lumen. We investigated the extent to which ABCR deficiency affects post-bleach recovery of the rod photoresponse in ABCR-deficient (abcr−/−) mice. Methods Electroretinographic (ERG) a-wave responses were recorded from abcr−/− mice and two control strains. Using a bright probe flash, we examined the course of rod recovery following fractional rhodopsin bleaches of ~10−6, ~3×10−5, ~0.03 and ~0.30–0.40. Results Dark-adapted abcr−/− mice and controls exhibited similar normalized near-peak amplitudes of the paired-flash-ERG-derived, weak-flash response. Response recovery following ~10−6 bleaching exhibited an average exponential time constant of 319, 171 and 213 ms, respectively, in the abcr−/− and the two control strains. Recovery time constants determined for ~3×10−5 bleaching did not differ significantly among strains. However, those determined for the ~0.03 bleach indicated significantly faster recovery in abcr−/− (2.34 ± 0.74 min) than in the controls (5.36 ± 2.20 min, and 5.92 ± 2.44 min). Following ~0.30–0.40 bleaching, the initial recovery in the abcr−/− was on average faster than in controls. Conclusions By comparison with controls, abcr−/− mice exhibit faster rod recovery following a bleach of ~0.03. The data suggest that ABCR in normal rods may directly or indirectly prolong all-trans retinal clearance from the disk lumen over a significant bleaching range, and that the essential function of ABCR may be to promote the clearance of residual amounts of all-trans retinal that remain in the disks long after bleaching. PMID:18263807

A neuronal circuit for colour vision based on rod-cone opponency.

PubMed

Joesch, Maximilian; Meister, Markus

2016-04-14

In bright light, cone-photoreceptors are active and colour vision derives from a comparison of signals in cones with different visual pigments. This comparison begins in the retina, where certain retinal ganglion cells have 'colour-opponent' visual responses-excited by light of one colour and suppressed by another colour. In dim light, rod-photoreceptors are active, but colour vision is impossible because they all use the same visual pigment. Instead, the rod signals are thought to splice into retinal circuits at various points, in synergy with the cone signals. Here we report a new circuit for colour vision that challenges these expectations. A genetically identified type of mouse retinal ganglion cell called JAMB (J-RGC), was found to have colour-opponent responses, OFF to ultraviolet (UV) light and ON to green light. Although the mouse retina contains a green-sensitive cone, the ON response instead originates in rods. Rods and cones both contribute to the response over several decades of light intensity. Remarkably, the rod signal in this circuit is antagonistic to that from cones. For rodents, this UV-green channel may play a role in social communication, as suggested by spectral measurements from the environment. In the human retina, all of the components for this circuit exist as well, and its function can explain certain experiences of colour in dim lights, such as a 'blue shift' in twilight. The discovery of this genetically defined pathway will enable new targeted studies of colour processing in the brain.

Salamander Saver

ERIC Educational Resources Information Center

Ilseman, Kelly; Hoffmann, Kristine

2016-01-01

On a spring morning in Maine, traps made of nets rise above vernal pools in a small wetland, ready to collect salamanders. The traps were designed by groups of rural and urban high school students from Maine and Massachusetts participating in the University of Maine Upward Bound Math Science Program (UBMS) at the university campus in Orono, Maine.…

Sodium-bicarbonate cotransport in retinal Müller (glial) cells of the salamander.

PubMed

Newman, E A

1991-12-01

An electrogenic Na+/HCO3- cotransport system was studied in freshly dissociated Müller cells of the salamander retina. Cotransporter currents were recorded from isolated cells using the whole-cell, voltage-clamp technique following the block of K+ conductance with external Ba2+ and internal Cs+. At constant pHo, an outward current was evoked when extracellular HCO3- concentration was raised by pressure ejecting a HCO3(-)-buffered solution onto the surface of cells bathed in nominally HCO3(-)-free solution. The HCO3(-)-evoked outward current was reduced to 4.4% of control by 0.5 mM DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonate), to 28.8% of control by 2 mM DNDS (4,4'-dinitrostilbene-2,2'-disulfonate), and to 28.4% of control by 2 mM harmaline. Substitution of choline for Na+ in bath and ejection solutions reduced the response to 1.3% of control. Bicarbonate-evoked currents of normal magnitude were recorded when methane sulfonate was substituted for Cl- in bath, ejection, and intracellular solutions. Similarly, an outward current was evoked when extracellular Na+ concentration was raised in the presence of HCO3-. The Na(+)-evoked response was reduced to 16.2% of control by 2 mM DNDS and was abolished by removal of HCO3- from bath and ejection solutions. Taken together, these results (block by stilbenes and harmaline, HCO3- and Na+ dependence, Cl- independence) indicate that salamander Müller cells possess an electrogenic Na+/HCO3- cotransport system. Na+/HCO3- cotransporter sites were localized primarily at the endfoot region of Müller cells. Ejection of HCO3- onto the endfoot evoked outward currents 10 times larger than currents evoked by ejections onto the opposite (distal) end of the cell. The reversal potential of the cotransporter was determined by DNDS block of cotransport current. In the absence of a transmembrane HCO3- gradient, the reversal potential varied systematically as a function of the transmembrane Na+ gradient. The reversal potential was

Predicting variation in microhabitat utilization of terrestrial salamanders

Treesearch

Katherine M. O' Donnell; Frank R. Thompson; Raymond D. Semlitsch

2014-01-01

Understanding patterns of microhabitat use among terrestrial salamanders is important for predicting their responses to natural and anthropogenic disturbances. The dependence of terrestrial salamanders on cutaneous respiration limits their spatial distribution to moist, humid areas. Although many studies have shown negative effects of canopy removal on terrestrial...

Multiple rod-cone and cone-rod photoreceptor transmutations in snakes: evidence from visual opsin gene expression.

PubMed

Simões, Bruno F; Sampaio, Filipa L; Loew, Ellis R; Sanders, Kate L; Fisher, Robert N; Hart, Nathan S; Hunt, David M; Partridge, Julian C; Gower, David J

2016-01-27

In 1934, Gordon Walls forwarded his radical theory of retinal photoreceptor 'transmutation'. This proposed that rods and cones used for scotopic and photopic vision, respectively, were not fixed but could evolve into each other via a series of morphologically distinguishable intermediates. Walls' prime evidence came from series of diurnal and nocturnal geckos and snakes that appeared to have pure-cone or pure-rod retinas (in forms that Walls believed evolved from ancestors with the reverse complement) or which possessed intermediate photoreceptor cells. Walls was limited in testing his theory because the precise identity of visual pigments present in photoreceptors was then unknown. Subsequent molecular research has hitherto neglected this topic but presents new opportunities. We identify three visual opsin genes, rh1, sws1 and lws, in retinal mRNA of an ecologically and taxonomically diverse sample of snakes central to Walls' theory. We conclude that photoreceptors with superficially rod- or cone-like morphology are not limited to containing scotopic or photopic opsins, respectively. Walls' theory is essentially correct, and more research is needed to identify the patterns, processes and functional implications of transmutation. Future research will help to clarify the fundamental properties and physiology of photoreceptors adapted to function in different light levels. © 2016 The Author(s).

Transient release kinetics of rod bipolar cells revealed by capacitance measurement of exocytosis from axon terminals in rat retinal slices.

PubMed

Oltedal, Leif; Hartveit, Espen

2010-05-01

Presynaptic transmitter release has mostly been studied through measurements of postsynaptic responses, but a few synapses offer direct access to the presynaptic terminal, thereby allowing capacitance measurements of exocytosis. For mammalian rod bipolar cells, synaptic transmission has been investigated in great detail by recording postsynaptic currents in AII amacrine cells. Presynaptic measurements of the dynamics of vesicular cycling have so far been limited to isolated rod bipolar cells in dissociated preparations. Here, we first used computer simulations of compartmental models of morphologically reconstructed rod bipolar cells to adapt the 'Sine + DC' technique for capacitance measurements of exocytosis at axon terminals of intact rod bipolar cells in retinal slices. In subsequent physiological recordings, voltage pulses that triggered presynaptic Ca(2+) influx evoked capacitance increases that were proportional to the pulse duration. With pulse durations 100 ms, the increase saturated at 10 fF, corresponding to the size of a readily releasable pool of vesicles. Pulse durations 400 ms evoked additional capacitance increases, probably reflecting recruitment from additional pools of vesicles. By using Ca(2+) tail current stimuli, we separated Ca(2+) influx from Ca(2+) channel activation kinetics, allowing us to estimate the intrinsic release kinetics of the readily releasable pool, yielding a time constant of 1.1 ms and a maximum release rate of 2-3 vesicles (release site)(1) ms(1). Following exocytosis, we observed endocytosis with time constants ranging from 0.7 to 17 s. Under physiological conditions, it is likely that release will be transient, with the kinetics limited by the activation kinetics of the voltage-gated Ca(2+) channels.

Science Review for the Scott Bar Salamander (Plethodon asupak) and the Siskiyou Mountains Salamander (P. stormi): Biology, Taxonomy, Habitat, and Detection Probabilities/Occupancy

USGS Publications Warehouse

DeGross, Douglas J.; Bury, R. Bruce

2007-01-01

The Plethodon elongatus Complex in the Klamath-Siskiyou Ecoregion of southern Oregon and northern California includes three species: the Del Norte salamander, Plethodon elongatus; the Siskiyou Mountains salamander, P. stormi; and the Scott Bar salamander, P. asupak. This review aims to summarize the current literature and information available on select topics for P. stormi and P. asupak. These are both terrestrial salamanders belonging to the Family Plethodontidae, which contains more species and has a wider geographic distribution than any other family of salamanders (Wake 1966, 2006; Pough 1989). The genera of this family have greatly diversified ecologically across North America, Central America, northern South America, Sardinia, southeastern France and northwestern Italy, and have recently been discovered on the Korean peninsula (Min et al. 2005). The genus Plethodon is found exclusively in North America and is split into three distinct clades, based upon morphology and phylogenetics (Highton and Larson 1979): eastern small Plethodon, eastern large Plethodon, and the western Plethodon. The western Plethodon are the greatest representation of Plethodontidae in the Pacific Northwest, with 8 species. The two species with the most restricted ranges of these regional congeners are the Siskiyou Mountains and Scott Bar salamanders. These salamanders occupy the interior of the Klamath-Siskiyou Ecoregion which straddles the California and Oregon state lines, between Siskiyou County (CA) and Jackson and Josephine Counties (OR). The relatively recent discovery of P. asupak (Mead et al. 2005) and the limited range of both species have created an environment of uncertain conservation status for these species. This review will focus on four central topics of concern for land and resource managers: Biology; Taxonomy; Habitat; and Detection Probabilities/Occupancy.

The retina visual cycle is driven by cis retinol oxidation in the outer segments of cones

PubMed Central

Sato, Shinya; Frederiksen, Rikard; Cornwall, M. Carter; Kefalov, Vladimir J.

2017-01-01

Vertebrate rod and cone photoreceptors require continuous supply of chromophore for regenerating their visual pigments after photoactivation. Cones, which mediate our daytime vision, demand a particularly rapid supply of 11-cis retinal chromophore in order to maintain their function in bright light. An important contribution to this process is thought to be the chromophore precursor 11-cis retinol, which is supplied to cones from Müller cells in the retina and subsequently oxidized to 11-cis retinal as part of the retina visual cycle. However, the molecular identity of the cis retinol oxidase in cones remains unclear. Here, as a first step in characterizing this enzymatic reaction, we sought to determine the subcellular localization of this activity in salamander red cones. We found that the onset of dark adaptation of isolated salamander red cones was substantially faster when exposing directly their outer vs. their inner segment to 9-cis retinol, an analogue of 11-cis retinol. In contrast, this difference was not observed when treating the outer vs. inner segment with 9-cis retinal, a chromophore analogue which can directly support pigment regeneration. These results suggest, surprisingly, that the cis-retinol oxidation occurs in the outer segments of cone photoreceptors. Confirming this notion, pigment regeneration with exogenously added 9-cis retinol was directly observed in the truncated outer segments of cones, but not in rods. We conclude that the enzymatic machinery required for the oxidation of recycled cis retinol as part of the retina visual cycle is present in the outer segments of cones. PMID:28359344

Native salamanders and introduced fish: Changing the nature of mountain lakes and ponds

USGS Publications Warehouse

Larson, Gary L.; Hoffman, Robert L.

2003-01-01

During the last century, many fishless mountain lakes and ponds in the Pacific Northwest were stocked with non-native fish, such as brook trout, for recreational purposes. These introduced fish replaced long-toed and northwestern salamander larvae as the top aquatic vertebrate predator by preying on salamander larvae. This predatory interaction has been shown to reduce the abundances of larval salamander populations. We conducted studies in two national parks to assess the abundances of salamander larvae in lakes with and without introduced fish. These studies suggest that the two salamander species were affected quite differently by the presence of introduced fish because of different life-history traits and different distributions of salamanders and fish within each park.

Light adaptation does not prevent early retinal abnormalities in diabetic rats

PubMed Central

Kur, Joanna; Burian, Michael A.; Newman, Eric A.

2016-01-01

The aetiology of diabetic retinopathy (DR), the leading cause of blindness in the developed world, remains controversial. One hypothesis holds that retinal hypoxia, exacerbated by the high O2 consumption of rod photoreceptors in the dark, is a primary cause of DR. Based on this prediction we investigated whether early retinal abnormalities in streptozotocin-induced diabetic rats are alleviated by preventing the rods from dark adapting. Diabetic rats and their non-diabetic littermates were housed in a 12:12 hour light-dim light photocycle (30 lux during the day and 3 lux at night). Progression of early retinal abnormalities in diabetic rats was assessed by monitoring the ERG b-wave and oscillatory potentials, Müller cell reactive gliosis, and neuronal cell death, as assayed by TUNEL staining and retinal thickness at 6 and 12 weeks after diabetes induction. Maintaining diabetic animals in a dim-adapting light did not slow the progression of these neuronal and glial changes when compared to diabetic rats maintained in a standard 12:12 hour light-dark photocycle (30 lux during the day and 0 lux at night). Our results indicate that neuronal and glial abnormalities in early stages of diabetes are not exacerbated by rod photoreceptor O2 consumption in the dark. PMID:26852722

Developing rods transplanted into the degenerating retina of Crx-knockout mice exhibit neural activity similar to native photoreceptors

PubMed Central

Homma, Kohei; Okamoto, Satoshi; Mandai, Michiko; Gotoh, Norimoto; Rajasimha, Harsha K.; Chang, Yi-Sheng; Chen, Shan; Li, Wei; Cogliati, Tiziana; Swaroop, Anand; Takahashi, Masayo

2013-01-01

Replacement of dysfunctional or dying photoreceptors offers a promising approach for retinal neurodegenerative diseases, including age-related macular degeneration and retinitis pigmentosa. Several studies have demonstrated the integration and differentiation of developing rod photoreceptors when transplanted in wild type or degenerating retina; however, the physiology and function of the donor cells are not adequately defined. Here, we describe the physiological properties of developing rod photoreceptors that are tagged with GFP driven by the promoter of rod differentiation factor, Nrl. GFP-tagged developing rods show Ca2+ responses and rectifier outward currents that are smaller than those observed in fully developed photoreceptors, suggesting their immature developmental state. These immature rods also exhibit hyperpolarization-activated current (Ih) induced by the activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. When transplanted into the subretinal space of wild type or retinal degeneration mice, GFP-tagged developing rods can integrate into the photoreceptor outer nuclear layer in wild-type mouse retina, and exhibit Ca2+ responses and membrane current comparable to native rod photoreceptors. A proportion of grafted rods develop rhodopsin-positive outer segment-like structures within two weeks after transplantation into the retina of Crx-knockout mice, and produce rectifier outward current and Ih upon membrane depolarization and hyperpolarization. GFP-positive rods derived from induced pluripotent stem (iPS) cells also display similar membrane current Ih as native developing rod photoreceptors, express rod-specific phototransduction genes, and HCN-1 channels. We conclude that Nrl-promoter driven GFP-tagged donor photoreceptors exhibit physiological characteristics of rods and that iPS cell-derived rods in vitro may provide a renewable source for cell replacement therapy. PMID:23495178

Local and landscape scale factors influencing edge effects on woodland salamanders.

PubMed

Moseley, Kurtis R; Ford, W Mark; Edwards, John W

2009-04-01

We examined local and landscape-scale variable influence on the depth and magnitude of edge effects on woodland salamanders in mature mixed mesophytic and northern hardwood forest adjacent to natural gas well sites maintained as wildlife openings. We surveyed woodland salamander occurrence from June-August 2006 at 33 gas well sites in the Monongahela National Forest, West Virginia. We used an information-theoretic approach to test nine a priori models explaining landscape-scale effects on woodland salamander capture proportion within 20 m of field edge. Salamander capture proportion was greater within 0-60 m than 61-100 m of field edges. Similarly, available coarse woody debris proportion was greater within 0-60 m than 61-100 m of field edge. Our ASPECT model, that incorporated the single variable aspect, received the strongest support for explaining landscape-scale effects on salamander capture proportion within 20 m of opening edge. The ASPECT model indicated that fewer salamanders occurred within 20 m of opening edges on drier, hotter southwestern aspects than in moister, cooler northeastern aspects. Our results suggest that forest habitat adjacent to maintained edges and with sufficient cover still can provide suitable habitat for woodland salamander species in central Appalachian mixed mesophytic and northern hardwood forests. Additionally, our modeling results support the contention that edge effects are more severe on southwesterly aspects. These results underscore the importance of distinguishing among different edge types as well as placing survey locations within a landscape context when investigating edge impacts on woodland salamanders.

Tiger salamanders' (Ambystoma tigrinum) response learning and usage of visual cues.

PubMed

Kundey, Shannon M A; Millar, Roberto; McPherson, Justin; Gonzalez, Maya; Fitz, Aleyna; Allen, Chadbourne

2016-05-01

We explored tiger salamanders' (Ambystoma tigrinum) learning to execute a response within a maze as proximal visual cue conditions varied. In Experiment 1, salamanders learned to turn consistently in a T-maze for reinforcement before the maze was rotated. All learned the initial task and executed the trained turn during test, suggesting that they learned to demonstrate the reinforced response during training and continued to perform it during test. In a second experiment utilizing a similar procedure, two visual cues were placed consistently at the maze junction. Salamanders were reinforced for turning towards one cue. Cue placement was reversed during test. All learned the initial task, but executed the trained turn rather than turning towards the visual cue during test, evidencing response learning. In Experiment 3, we investigated whether a compound visual cue could control salamanders' behaviour when it was the only cue predictive of reinforcement in a cross-maze by varying start position and cue placement. All learned to turn in the direction indicated by the compound visual cue, indicating that visual cues can come to control their behaviour. Following training, testing revealed that salamanders attended to stimuli foreground over background features. Overall, these results suggest that salamanders learn to execute responses over learning to use visual cues but can use visual cues if required. Our success with this paradigm offers the potential in future studies to explore salamanders' cognition further, as well as to shed light on how features of the tiger salamanders' life history (e.g. hibernation and metamorphosis) impact cognition.

Retinal adaptation to dim light vision in spectacled caimans (Caiman crocodilus fuscus): Analysis of retinal ultrastructure.

PubMed

Karl, Anett; Agte, Silke; Zayas-Santiago, Astrid; Makarov, Felix N; Rivera, Yomarie; Benedikt, Jan; Francke, Mike; Reichenbach, Andreas; Skatchkov, Serguei N; Bringmann, Andreas

2018-05-19

oblique arrangement of many Müller cell trunks/processes in the inner plexiform layer and the large Müller cell somata in the inner nuclear layer may suggest that light guidance through Müller cells increases the visual sensitivity. Furthermore, an adaptation of the caiman retina to low light levels is strongly supported by detailed ultrastructural data of other retinal parts, e.g. by (i) the presence of a guanine-based retinal tapetum, (ii) the rod dominance of the retina, (iii) the presence of photoreceptor cell nuclei, which penetrate the outer limiting membrane, (iv) the relatively low densities of photoreceptor and neuronal cells which is compensated by (v) the presence of rods with long and thick outer segments, that may increase the probability of photon absorption. According to a cell number analysis, the central and temporal areas of the dorsal tapetal retina, which supports downward prey detection in darker water, are the sites of the highest diurnal contrast/color vision, i.e. cone vision and of the highest retinal light sensitivity, i.e. rod vision. Copyright © 2018 Elsevier Ltd. All rights reserved.

Normal central retinal function and structure preserved in retinitis pigmentosa.

PubMed

Jacobson, Samuel G; Roman, Alejandro J; Aleman, Tomas S; Sumaroka, Alexander; Herrera, Waldo; Windsor, Elizabeth A M; Atkinson, Lori A; Schwartz, Sharon B; Steinberg, Janet D; Cideciyan, Artur V

2010-02-01

To determine whether normal function and structure, as recently found in forms of Usher syndrome, also occur in a population of patients with nonsyndromic retinitis pigmentosa (RP). Patients with simplex, multiplex, or autosomal recessive RP (n = 238; ages 9-82 years) were studied with static chromatic perimetry. A subset was evaluated with optical coherence tomography (OCT). Co-localized visual sensitivity and photoreceptor nuclear layer thickness were measured across the central retina to establish the relationship of function and structure. Comparisons were made to patients with Usher syndrome (n = 83, ages 10-69 years). Cross-sectional psychophysical data identified patients with RP who had normal rod- and cone-mediated function in the central retina. There were two other patterns with greater dysfunction, and longitudinal data confirmed that progression can occur from normal rod and cone function to cone-only central islands. The retinal extent of normal laminar architecture by OCT corresponded to the extent of normal visual function in patients with RP. Central retinal preservation of normal function and structure did not show a relationship with age or retained peripheral function. Usher syndrome results were like those in nonsyndromic RP. Regional disease variation is a well-known finding in RP. Unexpected was the observation that patients with presumed recessive RP can have regions with functionally and structurally normal retina. Such patients will require special consideration in future clinical trials of either focal or systemic treatment. Whether there is a common molecular mechanism shared by forms of RP with normal regions of retina warrants further study.

Alteration of rod and cone function in children with Usher syndrome.

PubMed

Malm, Eva; Ponjavic, Vesna; Möller, Claes; Kimberling, William J; Stone, Edwin S; Andréasson, Sten

2011-01-01

To evaluate the retinal function, with emphasis on phenotype and rate of progression, in infants and children with different genotypes of Usher syndrome. Fourteen children (2-10 years of age) with retinitis pigmentosa and hearing impairment were examined with full-field electroretinography (ERG) during general anesthesia, ophthalmologic examination, and genetic analysis. Five children were repeatedly examined (follow-up 5-10 years) with full-field ERG under local anesthesia and in 2 children multifocal ERG and optical coherence tomography (OCT) were performed. These results were compared to full-field ERG data from 58 children without retinal eye disorder. Six children were genotyped as Usher 1B, 2A, and 3A. Full-field ERG demonstrated early alterations corresponding to a rod-cone dystrophy in all children. A remaining rod function could be verified in the majority of the children up to 4 years of age. After 4 years of age, there was a further deterioration of the rod function; the progress was severe in Usher types 1 and 2 and moderate in Usher type 3. In all children, the cone function was moderately reduced, in a few cases almost normal. The results from the 58 children without retinal disorder confirm that full-field ERG during general anesthesia is reliable. Multifocal ERG confirmed a preserved central cone function and in OCT there were discrete structural alterations. Full-field ERG during general anesthesia in children with Usher syndrome demonstrates variable phenotypes and different degrees in rate of progression during childhood.

Detection of Batrachochytrium dendrobatidis in endemic salamander species from central Texas.

PubMed

Gaertner, James P; Forstner, Michael R J; O'Donnell, Lisa; Hahn, Dittmar

2009-03-01

A nested PCR protocol was used to analyze five endemic salamander species from Central Texas for the presence of the emerging pathogen, chytrid fungus (Batrachochytrium dendrobatidis). Chytrid fungus was detected from samples of each of the five species sampled: with low abundance, in the Texas salamander (Eurycea neotenes) (1 positive out of 16 individuals tested; 1/16), the Blanco River Springs salamander (E. pterophila) (1/20), the threatened San Marcos salamander (E. nana) (1/17), and the endangered Barton Springs salamander (E. sosorum) (1/7); much higher abundance was obtained for the Jollyville Plateau salamander (E. tonkawae) (6/14), which has recently been petitioned for addition to the USA endangered species list. With one exception, sequences of PCR products were identical to the 5.8S rRNA gene, and nearly so for the flanking internal transcribed spacer (ITS) regions of B. dendrobatidis which confirmed the detection of chytrid fungus, and thus demonstrated the presence of this pathogen in populations of endangered species in Central Texas. These confirmations were obtained from nonconsumptive tail clippings which confirms the applicability of historically collected samples from other studies in the examination of the fungus across time.

Lipofuscin and N-Retinylidene-N-Retinylethanolamine (A2E) Accumulate in Retinal Pigment Epithelium in Absence of Light Exposure

PubMed Central

Boyer, Nicholas P.; Higbee, Daniel; Currin, Mark B.; Blakeley, Lorie R.; Chen, Chunhe; Ablonczy, Zsolt; Crouch, Rosalie K.; Koutalos, Yiannis

2012-01-01

The age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) has been associated with the development of retinal diseases, particularly age-related macular degeneration and Stargardt disease. A major component of lipofuscin is the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). The current model for the formation of A2E requires photoactivation of rhodopsin and subsequent release of all-trans-retinal. To understand the role of light exposure in the accumulation of lipofuscin and A2E, we analyzed RPEs and isolated rod photoreceptors from mice of different ages and strains, reared either in darkness or cyclic light. Lipofuscin levels were determined by fluorescence imaging, whereas A2E levels were quantified by HPLC and UV-visible absorption spectroscopy. The identity of A2E was confirmed by tandem mass spectrometry. Lipofuscin and A2E levels in the RPE increased with age and more so in the Stargardt model Abca4−/− than in the wild type strains 129/sv and C57Bl/6. For each strain, the levels of lipofuscin precursor fluorophores in dark-adapted rods and the levels and rates of increase of RPE lipofuscin and A2E were not different between dark-reared and cyclic light-reared animals. Both 11-cis- and all-trans-retinal generated lipofuscin-like fluorophores when added to metabolically compromised rod outer segments; however, it was only 11-cis-retinal that generated such fluorophores when added to metabolically intact rods. The results suggest that lipofuscin originates from the free 11-cis-retinal that is continuously supplied to the rod for rhodopsin regeneration and outer segment renewal. The physiological role of Abca4 may include the translocation of 11-cis-retinal complexes across the disk membrane. PMID:22570475

Diagnostic and molecular evaluation of three iridovirus-associated salamander mortality events

USGS Publications Warehouse

Docherty, D.E.; Meteyer, C.U.; Wang, Jingyuan; Mao, J.; Case, S.T.; Chinchar, V.G.

2003-01-01

In 1998 viruses were isolated from tiger salamander larvae (Ambystoma tigrinum diaboli and A. tigrinum melanostictum) involved in North Dakota and Utah (USA) mortality events and spotted salamander (A. maculatum) larvae in a third event in Maine (USA). Although sympatric caudates and anurans were present at all three sites only ambystomid larvae appeared to be affected. Mortality at the North Dakota site was in the thousands while at the Utah and Maine sites mortality was in the hundreds. Sick larvae were lethargic and slow moving. They swam in circles with obvious buoyancy problems and were unable to remain upright. On the ventral surface, near the gills and hind limbs, red spots or swollen areas were noted. Necropsy findings included: hemorrhages and ulceration of the skin, subcutaneous and intramuscular edema, swollen and pale livers with multifocal hemorrhage, and distended fluid-filled intestines with areas of hemorrhage. Light microscopy revealed intracytoplasmic inclusions, suggestive of a viral infection, in a variety of organs. Electron microscopy of ultra thin sections of the same tissues revealed iridovirus-like particles within the inclusions. These viruses were isolated from a variety of organs, indicating a systemic infection. Representative viral isolates from the three mortality events were characterized using molecular assays. Characterization confirmed that the viral isolates were iridoviruses and that the two tiger salamander isolates were similar and could be distinguished from the spotted salamander isolate. The spotted salamander isolate was similar to frog virus 3, the type species of the genus Ranavirus, while the tiger salamander isolates were not. These data indicate that different species of salamanders can become infected and die in association with different iridoviruses. Challenge assays are required to determine the fish and amphibian host range of these isolates and to assess the susceptibility of tiger and spotted salamanders to

[Sulfhydryl group distribution along the axis of the rod outer segment in the frog].

PubMed

Derevianchenko, T G; Fedorovich, I B; Ostrovskiĭ, M A

1985-10-01

The existence of SH-group concentration axial gradient in frog's retinal rod outer segments has been shown. A diminution of SH-groups in the outer segment apical part points to a damage of the vision pigment during the life span of the rod disks.

Restoration of vision in the pde6β-deficient dog, a large animal model of rod-cone dystrophy.

PubMed

Petit, Lolita; Lhériteau, Elsa; Weber, Michel; Le Meur, Guylène; Deschamps, Jack-Yves; Provost, Nathalie; Mendes-Madeira, Alexandra; Libeau, Lyse; Guihal, Caroline; Colle, Marie-Anne; Moullier, Philippe; Rolling, Fabienne

2012-11-01

Defects in the β subunit of rod cGMP phosphodiesterase 6 (PDE6β) are associated with autosomal recessive retinitis pigmentosa (RP), a childhood blinding disease with early retinal degeneration and vision loss. To date, there is no treatment for this pathology. The aim of this preclinical study was to test recombinant adeno-associated virus (AAV)-mediated gene addition therapy in the rod-cone dysplasia type 1 (rcd1) dog, a large animal model of naturally occurring PDE6β deficiency that strongly resembles the human pathology. A total of eight rcd1 dogs were injected subretinally with AAV2/5RK.cpde6β (n = 4) or AAV2/8RK.cpde6β (n = 4). In vivo and post-mortem morphological analysis showed a significant preservation of the retinal structure in transduced areas of both AAV2/5RK.cpde6β- and AAV2/8RK.cpde6β-treated retinas. Moreover, substantial rod-derived electroretinography (ERG) signals were recorded as soon as 1 month postinjection (35% of normal eyes) and remained stable for at least 18 months (the duration of the study) in treated eyes. Rod-responses were undetectable in untreated contralateral eyes. Most importantly, dim-light vision was restored in all treated rcd1 dogs. These results demonstrate for the first time that gene therapy effectively restores long-term retinal function and vision in a large animal model of autosomal recessive rod-cone dystrophy, and provide great promise for human treatment.

Plethodon cinereus (Redback Salamander) predation

USGS Publications Warehouse

Jung, R.E.; Ward, W.L.; Kings, C.O.; Weir, L.A.

2000-01-01

In 1999 at the Patuxent Research Refuge, we observed a large rove beetle (Staphylinus maculosus) consuming an eviscerated redback salamander (Plethodon cinereus) underneath a coverboard. Rove beetles typically eat invertebrates.

Comparing population size estimators for plethodontid salamanders

USGS Publications Warehouse

Bailey, L.L.; Simons, T.R.; Pollock, K.H.

2004-01-01

Despite concern over amphibian declines, few studies estimate absolute abundances because of logistic and economic constraints and previously poor estimator performance. Two estimation approaches recommended for amphibian studies are mark-recapture and depletion (or removal) sampling. We compared abundance estimation via various mark-recapture and depletion methods, using data from a three-year study of terrestrial salamanders in Great Smoky Mountains National Park. Our results indicate that short-term closed-population, robust design, and depletion methods estimate surface population of salamanders (i.e., those near the surface and available for capture during a given sampling occasion). In longer duration studies, temporary emigration violates assumptions of both open- and closed-population mark-recapture estimation models. However, if the temporary emigration is completely random, these models should yield unbiased estimates of the total population (superpopulation) of salamanders in the sampled area. We recommend using Pollock's robust design in mark-recapture studies because of its flexibility to incorporate variation in capture probabilities and to estimate temporary emigration probabilities.

Characterization of the ecological requirements for three plethodontid salamander species

Treesearch

Jessica A. Wooten; William B. Sutton; Thomas K. Pauley

2010-01-01

Increased availability of habitat and climate data has facilitated much research concerning the influence of these characteristics on the structure of salamander communities. We aimed to outline environmental requirements influencing the distribution of three sympatric plethodontid salamander species, including Plethodon cinereus, Desmognathus ochrophaeus...

Evaluation of terrestrial and streamside salamander monitoring techniques at Shenandoah National Park

USGS Publications Warehouse

Jung, R.E.; Droege, S.; Sauer, J.R.; Landy, R.B.

2000-01-01

In response to concerns about amphibian declines, a study evaluating and validating amphibian monitoring techniques was initiated in Shenandoah and Big Bend National Parks in the spring of 1998. We evaluate precision, bias, and efficiency of several sampling methods for terrestrial and streamside salamanders in Shenandoah National Park and assess salamander abundance in relation to environmental variables, notably soil and water pH. Terrestrial salamanders, primarily redback salamanders (Plethodon cinereus), were sampled by searching under cover objects during the day in square plots (10 to 35 m2). We compared population indices (mean daily and total counts) with adjusted population estimates from capture-recapture. Analyses suggested that the proportion of salamanders detected (p) during sampling varied among plots, necessitating the use of adjusted population estimates. However, adjusted population estimates were less precise than population indices, and may not be efficient in relating salamander populations to environmental variables. In future sampling, strategic use of capture-recapture to verify consistency of p's among sites may be a reasonable compromise between the possibility of bias in estimation of population size and deficiencies due to inefficiency associated with the estimation of p. The streamside two-lined salamander (Eurycea bislineata) was surveyed using four methods: leaf litter refugia bags, 1 m2 quadrats, 50 x 1 m visual encounter transects, and electric shocking. Comparison of survey methods at nine streams revealed congruent patterns of abundance among sites, suggesting that relative bias among the methods is similar, and that choice of survey method should be based on precision and logistical efficiency. Redback and two-lined salamander abundance were not significantly related to soil or water pH, respectively.

Patch-clamp, ion-sensing, and glutamate-sensing techniques to study glutamate transport in isolated retinal glial cells.

PubMed

Billups, B; Szatkowski, M; Rossi, D; Attwell, D

1998-01-01

We have described how a combination of electrical, ion-sensing, and glutamate-sensing techniques has advanced our understanding of glutamate uptake into isolated salamander retinal glial cells. The next steps in understanding glutamate transport will inevitably depend strongly on molecular biological methods, as described elsewhere in this book, but will also require more detailed study of transporters in their normal environment, perhaps by using patch-clamping or imaging techniques to study cells in situ.

Reprogramming metabolism by targeting sirtuin 6 attenuates retinal degeneration

PubMed Central

Zhang, Lijuan; Du, Jianhai; Justus, Sally; Hsu, Chun-Wei; Bonet-Ponce, Luis; Wu, Wen-Hsuan; Tsai, Yi-Ting; Wu, Wei-Pu; Jia, Yading; Duong, Jimmy K.; Mahajan, Vinit B.; Lin, Chyuan-Sheng; Wang, Shuang; Hurley, James B.

2016-01-01

Retinitis pigmentosa (RP) encompasses a diverse group of Mendelian disorders leading to progressive degeneration of rods and then cones. For reasons that remain unclear, diseased RP photoreceptors begin to deteriorate, eventually leading to cell death and, consequently, loss of vision. Here, we have hypothesized that RP associated with mutations in phosphodiesterase-6 (PDE6) provokes a metabolic aberration in rod cells that promotes the pathological consequences of elevated cGMP and Ca2+, which are induced by the Pde6 mutation. Inhibition of sirtuin 6 (SIRT6), a histone deacetylase repressor of glycolytic flux, reprogrammed rods into perpetual glycolysis, thereby driving the accumulation of biosynthetic intermediates, improving outer segment (OS) length, enhancing photoreceptor survival, and preserving vision. In mouse retinae lacking Sirt6, effectors of glycolytic flux were dramatically increased, leading to upregulation of key intermediates in glycolysis, TCA cycle, and glutaminolysis. Both transgenic and AAV2/8 gene therapy–mediated ablation of Sirt6 in rods provided electrophysiological and anatomic rescue of both rod and cone photoreceptors in a preclinical model of RP. Due to the extensive network of downstream effectors of Sirt6, this study motivates further research into the role that these pathways play in retinal degeneration. Because reprogramming metabolism by enhancing glycolysis is not gene specific, this strategy may be applicable to a wide range of neurodegenerative disorders. PMID:27841758

GUCY2D Cone-Rod Dystrophy-6 Is a "Phototransduction Disease" Triggered by Abnormal Calcium Feedback on Retinal Membrane Guanylyl Cyclase 1.

PubMed

Sato, Shinya; Peshenko, Igor V; Olshevskaya, Elena V; Kefalov, Vladimir J; Dizhoor, Alexander M

2018-03-21

The Arg838Ser mutation in retinal membrane guanylyl cyclase 1 (RetGC1) has been linked to autosomal dominant cone-rod dystrophy type 6 (CORD6). It is believed that photoreceptor degeneration is caused by the altered sensitivity of RetGC1 to calcium regulation via guanylyl cyclase activating proteins (GCAPs). To determine the mechanism by which this mutation leads to degeneration, we investigated the structure and function of rod photoreceptors in two transgenic mouse lines, 362 and 379, expressing R838S RetGC1. In both lines, rod outer segments became shorter than in their nontransgenic siblings by 3-4 weeks of age, before the eventual photoreceptor degeneration. Despite the shortening of their outer segments, the dark current of transgenic rods was 1.5-2.2-fold higher than in nontransgenic controls. Similarly, the dim flash response amplitude in R838S + rods was larger, time to peak was delayed, and flash sensitivity was increased, all suggesting elevated dark-adapted free cGMP in transgenic rods. In rods expressing R838S RetGC1, dark-current noise increased and the exchange current, detected after a saturating flash, became more pronounced. These results suggest disrupted Ca 2+ phototransduction feedback and abnormally high free-Ca 2+ concentration in the outer segments. Notably, photoreceptor degeneration, which typically occurred after 3 months of age in R838S RetGC1 transgenic mice in GCAP1,2 +/+ or GCAP1,2 +/- backgrounds, was prevented in GCAP1,2 -/- mice lacking Ca 2+ feedback to guanylyl cyclase. In summary, the dysregulation of guanylyl cyclase in RetGC1-linked CORD6 is a "phototransduction disease," which means it is associated with increased free-cGMP and Ca 2+ levels in photoreceptors. SIGNIFICANCE STATEMENT In a mouse model expressing human membrane guanylyl cyclase 1 (RetGC1, GUCY2D ), a mutation associated with early progressing congenital blindness, cone-rod dystrophy type 6 (CORD6), deregulates calcium-sensitive feedback of phototransduction to

Plethodontid salamander response to Silvilcultural Practices in Missouri Ozark forests

Treesearch

Laura A. Herbeck; David R. Larsen

1999-01-01

There is little information on the effects of tree harvest on salamander populations in the midwestern United States. We present data on plethodontid salamander densities in replicated stands of three forest age classes in the southeastern Ozarks of Missouri. Forest age classes consisted of regeneration-cut sites

Bone marrow–derived stem cells preserve cone vision in retinitis pigmentosa

PubMed Central

Smith, Lois E.H.

2004-01-01

Retinitis pigmentosa is a heritable group of blinding diseases resulting from loss of photoreceptors, primarily rods and secondarily cones, that mediate central vision. Loss of retinal vasculature is a presumed metabolic consequence of photoreceptor degeneration. A new study shows that autologous bone marrow–derived lineage-negative hematopoietic stem cells, which incorporate into the degenerating blood vessels in two murine models of retinitis pigmentosa, rd1 and rd10, prevent cone loss. The use of autologous bone marrow might avoid problems with rejection while preserving central cone vision in a wide variety of genetically disparate retinal degenerative diseases. PMID:15372096

Stream water temperature limits occupancy of salamanders in mid-Atlantic protected areas

USGS Publications Warehouse

Grant, Evan H. Campbell; Wiewel, Amber N. M.; Rice, Karen C.

2014-01-01

Stream ecosystems are particularly sensitive to urbanization, and tolerance of water-quality parameters is likely important to population persistence of stream salamanders. Forecasted climate and landscape changes may lead to significant changes in stream flow, chemical composition, and temperatures in coming decades. Protected areas where landscape alterations are minimized will therefore become increasingly important for salamander populations. We surveyed 29 streams at three national parks in the highly urbanized greater metropolitan area of Washington, DC. We investigated relationships among water-quality variables and occupancy of three species of stream salamanders (Desmognathus fuscus, Eurycea bislineata, and Pseudotriton ruber). With the use of a set of site-occupancy models, and accounting for imperfect detection, we found that stream-water temperature limits salamander occupancy. There was substantial uncertainty about the effects of the other water-quality variables, although both specific conductance (SC) and pH were included in competitive models. Our estimates of occupancy suggest that temperature, SC, and pH have some importance in structuring stream salamander distribution.

Modeling photo-bleaching kinetics to map local variations in rod rhodopsin density

NASA Astrophysics Data System (ADS)

Ehler, M.; Dobrosotskaya, J.; King, E. J.; Czaja, W.; Bonner, R. F.

2011-03-01

Localized rod photoreceptor and rhodopsin losses have been observed in post mortem histology both in normal aging and in age-related maculopathy. We propose to noninvasively map local rod rhodopsin density through analysis of the brightening of the underlying lipofuscin autofluorescence (LAF) in confocal scanning laser ophthalmoscopy (cSLO) imaging sequences starting in the dark adapted eye. The detected LAF increases as rhodopsin is bleached (time constant ~ 25sec) by the average retinal irradiance of the cSLO 488nm laser beam. We fit parameters of analytical expressions for the kinetics of rhodopsin bleaching that Lamb validated using electroretinogram recordings in human. By performing localized (~ 100μm) kinetic analysis, we create high resolution maps of the rhodopsin density. This new noninvasive imaging and analysis approach appears well-suited for measuring localized changes in the rod photoreceptors and correlating them at high spatial resolution with localized pathological changes of the retinal pigment epithelium (RPE) seen in steady-state LAF images.

Restoration of Vision in the pde6β-deficient Dog, a Large Animal Model of Rod-cone Dystrophy

PubMed Central

Petit, Lolita; Lhériteau, Elsa; Weber, Michel; Le Meur, Guylène; Deschamps, Jack-Yves; Provost, Nathalie; Mendes-Madeira, Alexandra; Libeau, Lyse; Guihal, Caroline; Colle, Marie-Anne; Moullier, Philippe; Rolling, Fabienne

2012-01-01

Defects in the β subunit of rod cGMP phosphodiesterase 6 (PDE6β) are associated with autosomal recessive retinitis pigmentosa (RP), a childhood blinding disease with early retinal degeneration and vision loss. To date, there is no treatment for this pathology. The aim of this preclinical study was to test recombinant adeno-associated virus (AAV)-mediated gene addition therapy in the rod-cone dysplasia type 1 (rcd1) dog, a large animal model of naturally occurring PDE6β deficiency that strongly resembles the human pathology. A total of eight rcd1 dogs were injected subretinally with AAV2/5RK.cpde6β (n = 4) or AAV2/8RK.cpde6β (n = 4). In vivo and post-mortem morphological analysis showed a significant preservation of the retinal structure in transduced areas of both AAV2/5RK.cpde6β- and AAV2/8RK.cpde6β-treated retinas. Moreover, substantial rod-derived electroretinography (ERG) signals were recorded as soon as 1 month postinjection (35% of normal eyes) and remained stable for at least 18 months (the duration of the study) in treated eyes. Rod-responses were undetectable in untreated contralateral eyes. Most importantly, dim-light vision was restored in all treated rcd1 dogs. These results demonstrate for the first time that gene therapy effectively restores long-term retinal function and vision in a large animal model of autosomal recessive rod-cone dystrophy, and provide great promise for human treatment. PMID:22828504

Retinitis pigmentosa and allied conditions today: a paradigm of translational research

PubMed Central

2010-01-01

Monogenic human retinal dystrophies are a group of disorders characterized by progressive loss of photoreceptor cells leading to visual handicap. Retinitis pigmentosa is a type of retinal dystrophy where degeneration of rod photoreceptors occurs at the early stages. At present, there are no available effective therapies to maintain or improve vision in patients affected with retinitis pigmentosa, but post-genomic studies are allowing the development of potential therapeutic approaches. This review summarizes current knowledge on genes that have been identified to be responsible for retinitis pigmentosa, the involvement of these genes in the different forms of the disorder, the role of the proteins encoded by these genes in retinal function, the utility of genotyping, and current efforts to develop novel therapies. PMID:20519033

Rod Photopigment Kinetics After Photodisruption of the Retinal Pigment Epithelium

PubMed Central

Masella, Benjamin D.; Hunter, Jennifer J.; Williams, David R.

2014-01-01

Purpose. Advances in retinal imaging have led to the discovery of long-lasting retinal changes caused by light exposures below published safety limits, including disruption of the RPE. To investigate the functional consequences of RPE disruption, we combined adaptive optics ophthalmoscopy with retinal densitometry. Methods. A modified adaptive optics scanning light ophthalmoscope (AOSLO) measured the apparent density and regeneration rate of rhodopsin in two macaques before and after four different 568-nm retinal radiant exposures (RREs; 400–3200 J/cm2). Optical coherence tomography (OCT) was used to measure the optical path length through the photoreceptor outer segments before and after RPE disruption. Results. All tested RREs caused visible RPE disruption. Apparent rhodopsin density was significantly reduced following 1600 (P = 0.01) and 3200 J/cm2 (P = 0.007) exposures. No significant change in apparent density was observed in response to 800 J/cm2. Surprisingly, exposure to 400 J/cm2 showed a significant increase in apparent density (P = 0.047). Rhodopsin recovery rate was not significantly affected by these RREs. Optical coherence tomography measurements showed a significant decrease in the optical path length through the photoreceptor outer segments for RREs above 800 J/cm2 (P < 0.001). Conclusions. At higher RREs, optical path length through the outer segments was reduced. However, the rate of photopigment regeneration was unchanged. While some ambiguity remains as to the correlation between measured reflectivity and absolute rhodopsin density; at the lowest RREs, RPE disruption appears not to be accompanied by a loss of apparent rhodopsin density, which would have been indicative of functional loss. PMID:25316724

Clinical characteristics and current therapies for inherited retinal degenerations.

PubMed

Sahel, José-Alain; Marazova, Katia; Audo, Isabelle

2014-10-16

Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307-316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod-cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone-rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Hypoxic preconditioning protects photoreceptors against light damage independently of hypoxia inducible transcription factors in rods.

PubMed

Kast, Brigitte; Schori, Christian; Grimm, Christian

2016-05-01

Hypoxic preconditioning protects photoreceptors against light-induced degeneration preserving retinal morphology and function. Although hypoxia inducible transcription factors 1 and 2 (HIF1, HIF2) are the main regulators of the hypoxic response, photoreceptor protection does not depend on HIF1 in rods. Here we used rod-specific Hif2a single and Hif1a;Hif2a double knockout mice to investigate the potential involvement of HIF2 in rods for protection after hypoxic preconditioning. To identify potential HIF2 target genes in rods we determined the retinal transcriptome of hypoxic control and rod-specific Hif2a knockouts by RNA sequencing. We show that rods do not need HIF2 for hypoxia-induced increased survival after light exposure. The transcriptomic analysis revealed a number of genes that are potentially regulated by HIF2 in rods; among those were Htra1, Timp3 and Hmox1, candidates that are interesting due to their connection to human degenerative diseases of the retina. We conclude that neither HIF1 nor HIF2 are required in photoreceptors for protection by hypoxic preconditioning. We hypothesize that HIF transcription factors may be needed in other cells to produce protective factors acting in a paracrine fashion on photoreceptor cells. Alternatively, hypoxic preconditioning induces a rod-intrinsic response that is independent of HIF transcription factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Loukoumasomes Are Distinct Subcellular Structures from Rods and Rings and Are Structurally Associated with MAP2 and the Nuclear Envelope in Retinal Cells

PubMed Central

Noble, Jake W.; Hunter, Diana V.; Roskelley, Calvin D.; Chan, Edward K. L.; Mills, Julia

2016-01-01

“Rods and rings” (RR) and loukoumasomes are similarly shaped, subcellular macromolecular structures with as yet unknown function. RR, so named because of their shape, are formed in response to inhibition in the GTP or CTP synthetic pathways and are highly enriched in the two key enzymes of the nucleotide synthetic pathway. Loukoumasomes also occur as linear and toroidal bodies and were initially inferred to be the same as RR, largely due to their shared shape and size and the fact that it was unclear if they shared the same subcomponents. In human retinoblastoma tissue and cells we have observed toroidal, perinuclear, macromolecular structures of similar size and antigenicity to those previously reported in neurons (neuronal-loukoumasomes). To further characterize the subcomponents of the retinal-loukoumasomes, confocal analysis following immunocytochemical staining for alpha-tubulin, beta-III tubulin and detyrosinated tubulin was performed. These studies indicate that retinal-loukoumasomes are enriched for beta-III tubulin and other tubulins associated with microtubules. Immunofluorescence together with the in situ proximity ligation assay (PLA), confirmed that beta-III tubulin colocalized with detyrosinated tubulin within loukoumasomes. Our results indicate that these tissues contain only loukoumasomes because these macromolecular structures are immunoreactive with an anti-tubulin antibody but are not recognized by the prototype anti-RR/inosine monophosphate dehydrogenase (IMPDH) antibody (It2006). To further compare the RR and retinal-loukoumasomes, retinoblastoma cells were exposed to the IMPDH-inhibitor ribavirin, a drug known to induce the formation of RR. In contrast to RR, the production of retinal-loukoumasomes was unaffected. Coimmunostaining of Y79 cells for beta-III tubulin and IMPDH indicate that these cells, when treated with ribavirin, can contain both retinal-loukoumasomes and RR and that these structures are antigenically distinct. Subcellular

Loukoumasomes Are Distinct Subcellular Structures from Rods and Rings and Are Structurally Associated with MAP2 and the Nuclear Envelope in Retinal Cells.

PubMed

Noble, Jake W; Hunter, Diana V; Roskelley, Calvin D; Chan, Edward K L; Mills, Julia

2016-01-01

"Rods and rings" (RR) and loukoumasomes are similarly shaped, subcellular macromolecular structures with as yet unknown function. RR, so named because of their shape, are formed in response to inhibition in the GTP or CTP synthetic pathways and are highly enriched in the two key enzymes of the nucleotide synthetic pathway. Loukoumasomes also occur as linear and toroidal bodies and were initially inferred to be the same as RR, largely due to their shared shape and size and the fact that it was unclear if they shared the same subcomponents. In human retinoblastoma tissue and cells we have observed toroidal, perinuclear, macromolecular structures of similar size and antigenicity to those previously reported in neurons (neuronal-loukoumasomes). To further characterize the subcomponents of the retinal-loukoumasomes, confocal analysis following immunocytochemical staining for alpha-tubulin, beta-III tubulin and detyrosinated tubulin was performed. These studies indicate that retinal-loukoumasomes are enriched for beta-III tubulin and other tubulins associated with microtubules. Immunofluorescence together with the in situ proximity ligation assay (PLA), confirmed that beta-III tubulin colocalized with detyrosinated tubulin within loukoumasomes. Our results indicate that these tissues contain only loukoumasomes because these macromolecular structures are immunoreactive with an anti-tubulin antibody but are not recognized by the prototype anti-RR/inosine monophosphate dehydrogenase (IMPDH) antibody (It2006). To further compare the RR and retinal-loukoumasomes, retinoblastoma cells were exposed to the IMPDH-inhibitor ribavirin, a drug known to induce the formation of RR. In contrast to RR, the production of retinal-loukoumasomes was unaffected. Coimmunostaining of Y79 cells for beta-III tubulin and IMPDH indicate that these cells, when treated with ribavirin, can contain both retinal-loukoumasomes and RR and that these structures are antigenically distinct. Subcellular

Bright flash response recovery of mammalian rods in vivo is rate limited by RGS9

PubMed Central

Peinado Allina, Gabriel; Fortenbach, Christopher; Gross, Owen P.; Pugh, Edward N.

2017-01-01

The temporal resolution of scotopic vision is thought to be constrained by the signaling kinetics of retinal rods, which use a highly amplified G-protein cascade to transduce absorbed photons into changes in membrane potential. Much is known about the biochemical mechanisms that determine the kinetics of rod responses ex vivo, but the rate-limiting mechanisms in vivo are unknown. Using paired flash electroretinograms with improved signal-to-noise, we have recorded the amplitude and kinetics of rod responses to a wide range of flash strengths from living mice. Bright rod responses in vivo recovered nearly twice as fast as all previous recordings, although the kinetic consequences of genetic perturbations previously studied ex vivo were qualitatively similar. In vivo, the dominant time constant of recovery from bright flashes was dramatically reduced by overexpression of the RGS9 complex, revealing G-protein deactivation to be rate limiting for recovery. However, unlike previous ex vivo recordings, dim flash responses in vivo were relatively unaffected by RGS9 overexpression, suggesting that other mechanisms, such as calcium feedback dynamics that are strongly regulated by the restricted subretinal microenvironment, act to determine rod dim flash kinetics. To assess the consequences for scotopic vision, we used a nocturnal wheel-running assay to measure the ability of wild-type and RGS9-overexpressing mice to detect dim flickering stimuli and found no improvement when rod recovery was speeded by RGS9 overexpression. These results are important for understanding retinal circuitry, in particular as modeled in the large literature that addresses the relationship between the kinetics and sensitivity of retinal responses and visual perception. PMID:28302678

Rod- and cone-driven responses in mice expressing human L-cone pigment

PubMed Central

Atorf, Jenny; Neitz, Maureen; Neitz, Jay

2015-01-01

The mouse is commonly used for studying retinal processing, primarily because it is amenable to genetic manipulation. To accurately study photoreceptor driven signals in the healthy and diseased retina, it is of great importance to isolate the responses of single photoreceptor types. This is not easily achieved in mice because of the strong overlap of rod and M-cone absorption spectra (i.e., maxima at 498 and 508 nm, respectively). With a newly developed mouse model (Opn1lwLIAIS) expressing a variant of the human L-cone pigment (561 nm) instead of the mouse M-opsin, the absorption spectra are substantially separated, allowing retinal physiology to be studied using silent substitution stimuli. Unlike conventional chromatic isolation methods, this spectral compensation approach can isolate single photoreceptor subtypes without changing the retinal adaptation. We measured flicker electroretinograms in these mutants under ketamine-xylazine sedation with double silent substitution (silent S-cone and either rod or M/L-cones) and obtained robust responses for both rods and (L-)cones. Small signals were yielded in wild-type mice, whereas heterozygotes exhibited responses that were generally intermediate to both. Fundamental response amplitudes and phase behaviors (as a function of temporal frequency) in all genotypes were largely similar. Surprisingly, isolated (L-)cone and rod response properties in the mutant strain were alike. Thus the LIAIS mouse warrants a more comprehensive in vivo assessment of photoreceptor subtype-specific physiology, because it overcomes the hindrance of overlapping spectral sensitivities present in the normal mouse. PMID:26245314

Woodland salamander responses to a shelterwood harvest-prescribed burn silvicultural treatment within Appalachian mixed-oak forests

USGS Publications Warehouse

Ford, W. Mark; Mahoney, Kathleen R.; Russell, Kevin R.; Rodrigue, Jane L.; Riddle, Jason D.; Schuler, Thomas M.; Adams, Mary Beth

2015-01-01

Forest management practices that mimic natural canopy disturbances, including prescribed fire and timber harvests, may reduce competition and facilitate establishment of favorable vegetative species within various ecosystems. Fire suppression in the central Appalachian region for almost a century has contributed to a transition from oak-dominated to more mesophytic, fire-intolerant forest communities. Prescribed fire coupled with timber removal is currently implemented to aid in oak regeneration and establishment but responses of woodland salamanders to this complex silvicultural system is poorly documented. The purpose of our research was to determine how woodland salamanders respond to shelterwood harvests following successive burns in a central Appalachian mixed-oak forest. Woodland salamanders were surveyed using coverboard arrays in May, July, and August–September 2011 and 2012. Surveys were conducted within fenced shelterwood-burn (prescribed fires, shelterwood harvest, and fencing to prevent white-tailed deer [Odocoileus virginianus] herbivory), shelterwood-burn (prescribed fires and shelterwood harvest), and control plots. Relative abundance was modeled in relation to habitat variables measured within treatments for mountain dusky salamanders (Desmognathus ochrophaeus), slimy salamanders (Plethodon glutinosus), and eastern red-backed salamanders (Plethodon cinereus). Mountain dusky salamander relative abundance was positively associated with canopy cover and there were significantly more individuals within controls than either shelterwood-burn or fenced shelterwood-burn treatments. Conversely, habitat variables associated with slimy salamanders and eastern red-backed salamanders did not differ among treatments. Salamander age-class structure within controls did not differ from shelterwood-burn or fenced shelterwood-burn treatments for any species. Overall, the woodland salamander assemblage remained relatively intact throughout the shelterwoodburn

Retinal findings in a patient of French ancestry with CABP4-related retinal disease.

PubMed

Smirnov, Vasily Mikhaïlovitch; Zeitz, Christina; Soumittra, Nagasamy; Audo, Isabelle; Defoort-Dhellemmes, Sabine

2018-04-01

CABP4-related retinal dysfunction is a cone-rod synaptic transmission disorder with electronegative electroretinogram (ERG) waveform. It is a rare retinal dysfunction that can be classified into the incomplete form of congenital stationary night blindness. Absent foveal reflex and overall foveal thinning were previously reported, but in most cases the fundus appearance was described as nearly normal. We report here peculiar macular changes in a patient of French ancestry harbouring CABP4 mutations. Complete ocular examination and full-field ERG were performed at the initial presentation and follow-up. Multimodal fundus imagining, including spectral-domain optical coherence tomography, colour, infrared reflectance and short-wavelength autofluorescence photographs, was performed during follow-up visits. A 7-month-old infant was addressed to our department for visual unresponsiveness and nystagmus. ERG had an electronegative waveform, even for light-adapted stimuli, thus supporting the diagnosis of photoreceptor-bipolar cell transmission disorder. Genetic investigations discovered a compound heterozygous mutation in CABP4: c.646C > T, p.Arg216*/c.673C > T, p.Arg225*. Multimodal fundus imaging, performed at follow-up visits, showed fine radial folds at the vitreomacular interface and dark foveal dots in both eyes. Optic coherence tomography revealed a focal foveal ellipsoid zone gap. Initial presentation was misleading with Leber congenital amaurosis. The electronegative ERG waveform reoriented the genetic investigations and thus establishing a correct diagnosis. To the best of our knowledge, the peculiar fundus changes observed in our patient were never reported before. We hypothesized that a foveal ellipsoid zone interruption discovered in our patient could reflect mostly a cone dysfunction. It was unclear whether the fine radial folds in both maculae were linked with high hyperopia or were an intrinsic feature of the retinal disease. CABP4-related retinal

Effects of host species and environment on the skin microbiome of Plethodontid salamanders

USGS Publications Warehouse

Muletz-Wolz, Carly R.; Yarwood, Stephanie A.; Grant, Evan H. Campbell; Fleischer, Robert C.; Lips, Karen R.

2018-01-01

The amphibian skin microbiome is recognized for its role in defence against pathogens, including the deadly fungal pathogen Batrachochytrium dendrobatidis (Bd). Yet, we have little understanding of evolutionary and ecological processes that structure these communities, especially for salamanders and closely related species. We investigated patterns in the distribution of bacterial communities on Plethodon salamander skin across host species and environments.Quantifying salamander skin microbiome structure contributes to our understanding of how host-associated bacteria are distributed across the landscape, among host species, and their putative relationship with disease.We characterized skin microbiome structure (alpha-diversity, beta-diversity and bacterial operational taxonomic unit [OTU] abundances) using 16S rRNA gene sequencing for co-occurring Plethodon salamander species (35 Plethodon cinereus, 17 Plethodon glutinosus, 10 Plethodon cylindraceus) at three localities to differentiate the effects of host species from environmental factors on the microbiome. We sampled the microbiome of P. cinereus along an elevational gradient (n = 50, 700–1,000 m a.s.l.) at one locality to determine whether elevation predicts microbiome structure. Finally, we quantified prevalence and abundance of putatively anti-Bd bacteria to determine if Bd-inhibitory bacteria are dominant microbiome members.Co-occurring salamanders had similar microbiome structure, but among sites salamanders had dissimilar microbiome structure for beta-diversity and abundance of 28 bacterial OTUs. We found that alpha-diversity increased with elevation, beta-diversity and the abundance of 17 bacterial OTUs changed with elevation (16 OTUs decreasing, 1 OTU increasing). We detected 11 putatively anti-Bd bacterial OTUs that were present on 90% of salamanders and made up an average relative abundance of 83% (SD ± 8.5) per salamander. All salamanders tested negative for Bd.We conclude that

Tissue inhibitor of metalloproteinases 1 enhances rod survival in the rd1 mouse retina.

PubMed

Kim, Hwa Sun; Vargas, Andrew; Eom, Yun Sung; Li, Justin; Yamamoto, Kyra L; Craft, Cheryl Mae; Lee, Eun-Jin

2018-01-01

Retinitis pigmentosa (RP), an inherited retinal degenerative disease, is characterized by a progressive loss of rod photoreceptors followed by loss of cone photoreceptors. Previously, when tissue inhibitor of metalloproteinase 1 (TIMP1), a key extracellular matrix (ECM) regulator that binds to and inhibits activation of Matrix metallopeptidase 9 (MMP9) was intravitreal injected into eyes of a transgenic rhodopsin rat model of RP, S334ter-line3, we discovered cone outer segments are partially protected. In parallel, we reported that a specific MMP9 and MMP2 inhibitor, SB-3CT, interferes with mechanisms leading to rod photoreceptor cell death in an MMP9 dependent manner. Here, we extend our initial rat studies to examine the potential of TIMP1 as a treatment in retinal degeneration by investigating neuroprotective effects in a classic mouse retinal degeneration model, rdPde6b-/- (rd1). The results clearly demonstrate that intravitreal injections of TIMP1 produce extended protection to delay rod photoreceptor cell death. The mean total number of rods in whole-mount retinas was significantly greater in TIMP-treated rd1 retinas (postnatal (P) 30, P35 (P<0.0001) and P45 (P<0.05) than in saline-treated rd1 retinas. In contrast, SB-3CT did not delay rod cell death, leading us to further investigate alternative pathways that do not involve MMPs. In addition to inducing phosphorylated ERK1/2, TIMP1 significantly reduces BAX activity and delays attenuation of the outer nuclear layer (ONL). Physiological responses using scotopic electroretinograms (ERG) reveal b-wave amplitudes from TIMP1-treated retinas are significantly greater than from saline-treated rd1 retinas (P<0.05). In later degenerative stages of rd1 retinas, photopic b-wave amplitudes from TIMP1-treated rd1 retinas are significantly larger than from saline-treated rd1 retinas (P<0.05). Our findings demonstrate that TIMP1 delays photoreceptor cell death. Furthermore, this study provides new insights into how TIMP1

Moderate Light-Induced Degeneration of Rod Photoreceptors with Delayed Transducin Translocation in shaker1 Mice

PubMed Central

Zallocchi, Marisa; Wang, Wei-Min; Delimont, Duane; Cosgrove, Dominic

2011-01-01

Purpose. Usher syndrome is characterized by congenital deafness associated with retinitis pigmentosa (RP). Mutations in the myosin VIIa gene (MYO7A) cause a common and severe subtype of Usher syndrome (USH1B). Shaker1 mice have mutant MYO7A. They are deaf and have vestibular dysfunction but do not develop photoreceptor degeneration. The goal of this study was to investigate abnormalities of photoreceptors in shaker1 mice. Methods. Immunocytochemistry and hydroethidine-based detection of intracellular superoxide production were used. Photoreceptor cell densities under various conditions of light/dark exposures were evaluated. Results. In shaker1 mice, the rod transducin translocation is delayed because of a shift of its light activation threshold to a higher level. Even moderate light exposure can induce oxidative damage and significant rod degeneration in shaker1 mice. Shaker1 mice reared under a moderate light/dark cycle develop severe retinal degeneration in less than 6 months. Conclusions. These findings show that, contrary to earlier studies, shaker1 mice possess a robust retinal phenotype that may link to defective rod protein translocation. Importantly, USH1B animal models are likely vulnerable to light-induced photoreceptor damage, even under moderate light. PMID:21447681

Selective labeling of retinal ganglion cells with calcium indicators by retrograde loading in vitro

PubMed Central

Behrend, Matthew R.; Ahuja, Ashish K.; Humayun, Mark S.; Weiland, James D.; Chow, Robert H.

2012-01-01

Here we present a retrograde loading technique that makes it possible for the first time to rapidly load a calcium indicator in the majority of retinal ganglion cells (RGCs) in salamander retina, and then to observe physiological activity of these dye-loaded cells. Dextran-conjugated calcium indicator, dissolved in water, was applied to the optic nerve stump. Following dye loading, the isolated retina was mounted on a microelectrode array to demonstrate that electrical activity and calcium activity were preserved, as the retina responded to electrical stimuli. PMID:19428523

A new model of the spinal locomotor networks of a salamander and its properties.

PubMed

Liu, Qiang; Yang, Huizhen; Zhang, Jinxue; Wang, Jingzhuo

2018-05-22

A salamander is an ideal animal for studying the spinal locomotor network mechanism of vertebrates from an evolutionary perspective since it represents the transition from an aquatic to a terrestrial animal. However, little is known about the spinal locomotor network of a salamander. A spinal locomotor network model is a useful tool for exploring the working mechanism of the spinal networks of salamanders. A new spinal locomotor network model for a salamander is built for a three-dimensional (3D) biomechanical model of the salamander using a novel locomotion-controlled neural network model. Based on recent experimental data on the spinal circuitry and observational results of gaits of vertebrates, we assume that different interneuron sets recruited for mediating the frequency of spinal circuits are also related to the generation of different gaits. The spinal locomotor networks of salamanders are divided into low-frequency networks for walking and high-frequency networks for swimming. Additionally, a new topological structure between the body networks and limb networks is built, which only uses the body networks to coordinate the motion of limbs. There are no direct synaptic connections among limb networks. These techniques differ from existing salamander spinal locomotor network models. A simulation is performed and analyzed to validate the properties of the new spinal locomotor networks of salamanders. The simulation results show that the new spinal locomotor networks can generate a forward walking gait, a backward walking gait, a swimming gait, and a turning gait during swimming and walking. These gaits can be switched smoothly by changing external inputs from the brainstem. These properties are consistent with those of a real salamander. However, it is still difficult for the new spinal locomotor networks to generate highly efficient turning during walking, 3D swimming, nonrhythmic movements, and so on. New experimental data are required for further validation.

Reintroduction and Post-Release Survival of a Living Fossil: The Chinese Giant Salamander

PubMed Central

Zhang, Lu; Jiang, Wei; Wang, Qi-Jun; Zhao, Hu; Zhang, Hong-Xing; Marcec, Ruth M.; Willard, Scott T.; Kouba, Andrew J.

2016-01-01

Captive rearing and reintroduction / translocation are increasingly used as tools to supplement wild populations of threatened species. Reintroducing captive-reared Chinese giant salamanders may help to augment the declining wild populations and conserve this critically endangered amphibian. We released 31 captive-reared juvenile giant salamanders implanted with VHF radio transmitters at the Heihe River (n = 15) and the Donghe River (n = 16) in the Qinling Mountains of central China. Salamanders were monitored every day for survival from April 28th 2013 to September 3rd 2014. We attempted to recapture all living individuals by the end of the study, measured their body mass and total body length, and checked for abnormalities and presence of external parasites. Two salamanders at the Heihe River and 10 animals at the Donghe River survived through the project timeline. Nine salamanders were confirmed dead, while the status of the other 10 animals was undetermined. The annual survival rate of giant salamanders at the Donghe River (0.702) was 1.7-fold higher than that at the Heihe River (0.405). Survival increased as individuals were held longer following surgery, whereas body mass did not have a significant impact on survival rate. All salamanders recaptured from the Donghe River (n = 8) increased in mass (0.50 ± 0.13 kg) and length (5.5 ± 1.5 cm) after approximately 11 months in the wild, and they were only 7% lighter than wild animals of the same length (mean residual = -0.033 ± 0.025). Our results indicate that captive-reared Chinese giant salamanders can survive in the wild one year after release and adequate surgical recovery time is extremely important to post-release survival. Future projects may reintroduce older juveniles to achieve better survival and longer monitoring duration. PMID:27258650

A sign-reversing pathway from rods to double and single cones in the retina of the tiger salamander.

PubMed

Attwell, D; Werblin, F S; Wilson, M; Wu, S M

1983-03-01

Signal transmission between rods and cones was studied by passing current into a rod and recording the voltage response in a nearby double or single cone and vice versa. Two types of rod-cone interaction were found. Between immediately adjacent rods and cones, passage of current into either receptor elicited in the other receptor a sustained voltage response of the same sign as the injected current. These signals were still seen in the presence of Co2+, and are probably mediated by the electrical synapses which have been seen anatomically between adjacent rods and cones. In addition to this short-range sign-preserving interaction, passing current into a rod elicited a transient sign-inverted signal in cones up to at least 80 micron from the injected rod. No such response was seen in rods for current injection into cones. This signal was greatly reduced by Co2+ ions. Hyperpolarization of the cone to about -65 mV, with about 0.1 nA current, reversed this signal, which is presumed to be mediated by a chemical synaptic input to cones. Light flashes suppressed the sign-inverted signal for a period which was longer for brighter flashes. The time of reappearance of the signal was correlated with the return of the rod and horizontal cell potentials to their dark levels. This suppression could also be produced by an annulus of light which produced no light response in the receptors at the centre of the annulus, but which did polarize horizontal cells under the centre of the annulus. The wave form of the sign-inverted signal was similar to that produced in horizontal cells by current injection into rods, but of opposite sign. If an electrode was left in a cone for some time, the normal hyperpolarizing light response diminished, leaving a depolarizing response produced, presumably, by feed-back from horizontal cells. This signal was reversed when the cone was hyperpolarized with about 0.1 nA current. These data suggest that the sign-inverted response is mediated by feed

Seasonality and microhabitat selection in a forest-dwelling salamander

NASA Astrophysics Data System (ADS)

Basile, Marco; Romano, Antonio; Costa, Andrea; Posillico, Mario; Scinti Roger, Daniele; Crisci, Aldo; Raimondi, Ranieri; Altea, Tiziana; Garfì, Vittorio; Santopuoli, Giovanni; Marchetti, Marco; Salvidio, Sebastiano; De Cinti, Bruno; Matteucci, Giorgio

2017-10-01

Many small terrestrial vertebrates exhibit limited spatial movement and are considerably exposed to changes in local environmental variables. Among such vertebrates, amphibians at present experience a dramatic decline due to their limited resilience to environmental change. Since the local survival and abundance of amphibians is intrinsically related to the availability of shelters, conservation plans need to take microhabitat requirements into account. In order to gain insight into the terrestrial ecology of the spectacled salamander Salamandrina perspicillata and to identify appropriate forest management strategies, we investigated the salamander's seasonal variability in habitat use of trees as shelters in relation to tree features (size, buttresses, basal holes) and environmental variables in a beech forest in Italy. We used the occupancy approach to assess tree suitability on a non-conventional spatial scale. Our approach provides fine-grained parameters of microhabitat suitability and elucidates many aspects of the salamander's terrestrial ecology . Occupancy changed with the annual life cycle and was higher in autumn than in spring, when females were found closer to the stream in the study area. Salamanders showed a seasonal pattern regarding the trees they occupied and a clear preference for trees with a larger diameter and more burrows. With respect to forest management, we suggest maintaining a suitable number of trees with a trunk diameter exceeding 30 cm. A practice of selective logging along the banks of streams could help maintain an adequate quantity of the appropriate microhabitat. Furthermore, in areas with a presence of salamanders, a good forest management plan requires leaving an adequate buffer zone around streams, which should be wider in autumn than in spring.

77 FR 36287 - Proposed Low-Effect Habitat Conservation Plan for the California Tiger Salamander, Calaveras...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-18

...-FXES11120800000F2-123-F2] Proposed Low-Effect Habitat Conservation Plan for the California Tiger Salamander... animal, the threatened Central California Distinct Population Segment of the California tiger salamander (tiger salamander). The applicant would implement a conservation program to minimize and mitigate the...

Using passive integrated transponder (PIT) systems for terrestrial detection of blue-spotted salamanders (Ambystoma laterale) in situ

USGS Publications Warehouse

Ryan, Kevin J.; Zydlewski, Joseph D.; Calhoun, Aram J.K.

2014-01-01

Pure-diploid Blue-spotted Salamanders (Ambystoma laterale) are the smallest members of the family Ambystomatidae which makes tracking with radio-transmitters difficult because of small battery capacity. Passive integrated transponder (PIT) tags provide another tracking approach for small fossorial animals such as salamanders. We evaluated the use of portable PIT tag readers (PIT packs) to detect PIT tag-implanted pure-diploid Blue-spotted Salamanders in situ. We also examined the detection probability of salamanders with PIT tags held in enclosures in wetland and terrestrial habitats, as well as the underground detection range of PIT packs by scanning for buried tags not implanted into salamanders. Of the 532 PIT tagged salamanders, we detected 6.84% at least once during scanning surveys. We scanned systematically within a 13.37 ha area surrounding a salamander breeding pool on 34 occasions (~119 hours of survey time) and detected PIT tags 74 times. We detected 55% of PITs in tagged salamanders and 45%were expelled tags. We were able to reliably detect buried PIT tags from 1–22cm below the ground surface. Because nearly half the locations represented expelled tags, our data suggest this technique is inappropriate for future studies of pure-diploid Blue-spotted Salamanders, although it may be suitable for polyploid Blue-spotted Salamanders and other ambystomatid species, which are larger in size and may exhibit higher tag retention rates. It may also be prudent to conduct long-term tag retention studies in captivity before tagging and releasing salamanders for in situ study, and to double-mark individuals.

Chloride equilibrium potential in salamander cones

PubMed Central

Thoreson, Wallace B; Bryson, Eric J

2004-01-01

Background GABAergic inhibition and effects of intracellular chloride ions on calcium channel activity have been proposed to regulate neurotransmission from photoreceptors. To assess the impact of these and other chloride-dependent mechanisms on release from cones, the chloride equilibrium potential (ECl) was determined in red-sensitive, large single cones from the tiger salamander retinal slice. Results Whole cell recordings were done using gramicidin perforated patch techniques to maintain endogenous Cl- levels. Membrane potentials were corrected for liquid junction potentials. Cone resting potentials were found to average -46 mV. To measure ECl, we applied long depolarizing steps to activate the calcium-activated chloride current (ICl(Ca)) and then determined the reversal potential for the current component that was inhibited by the Cl- channel blocker, niflumic acid. With this method, ECl was found to average -46 mV. In a complementary approach, we used a Cl-sensitive dye, MEQ, to measure the Cl- flux produced by depolarization with elevated concentrations of K+. The membrane potentials produced by the various high K+ solutions were measured in separate current clamp experiments. Consistent with electrophysiological experiments, MEQ fluorescence measurements indicated that ECl was below -36 mV. Conclusions The results of this study indicate that ECl is close to the dark resting potential. This will minimize the impact of chloride-dependent presynaptic mechanisms in cone terminals involving GABAa receptors, glutamate transporters and ICl(Ca). PMID:15579212

At random meetings to the creation of new species of Salamander

NASA Astrophysics Data System (ADS)

Brillant, Marie-Pierre

2013-04-01

The pupils in final year of high school (15-18 years old) study the notion "species" and the creation of new species in various ways. Having studied genetic admixtures, this activity allows the pupils to build a scenario explaining the creation of a new species of Salamander in southern California from an ancestral population existing in northern Oregon. They can observe, on Google Earth, various populations of Salamander of the genus Ensatina. Salamanders of the genus Ensatina live in California around the Joaquin and Sacramento dry valleys. In this software, the pupils get information about the salamanders' environment and photographs of individuals and environments. During a migratory movement toward new territories to be colonized, these salamanders meet an inhospitable environment that they can not occupy. This population then splits up into two migratory branches, east and west, each overcoming the obstacles in different ways. The two groups gradually colonized southern territories but they avoided the too dry and hot San Joaquin plains. The two main branches of the original population gradually move away from each other, and genetic exchanges between them decrease over time. Eventually, we can find various populations of Salamander on both sides of the valleys, since the salamanders occupied new territories and diversified along the way. Among mutations that randomly occur, only those mutations that are best adapted in the origin were conserved in the genetic heritage of every population. When the individuals stemming from different western populations met, they were interfertile and give fertile hybrids, which was verified in the laboratory. Likewise, when individuals of the different eastern subspecies met accidentally, fertile hybrids also could arise from these crossings. The pupils can observe what happens in the overlap of various populations : interfertility or not. They also have geological, geographical and climatic information about the San Joaquin

Leaf litter bags as an index to populations of northern two-lined salamanders (Eurycea bislineata)

USGS Publications Warehouse

Chalmers, R.J.; Droege, S.

2002-01-01

Concern about recent amphibian declines has led to research on amphibian populations, but few statistically tested, standardized methods of counting amphibians exist. We tested whether counts of northern two-lined salamander larvae (Eurycea bislineata) sheltered in leaf litter bags--a relatively new, easily replicable survey technique--had a linear correlation to total number of larvae. Using experimental enclosures placed in streams, we compared number of salamanders found in artificial habitat (leaf litter bags) with total number of salamanders in each enclosure. Low numbers of the animals were found in leaf litter bags, and the relative amount of variation in the index (number of animals in leaf litter bags compared to total number of animals in stream enclosures) was high. The index of salamanders in leaf litter bags was not significantly related to total number of salamanders in enclosures for two-thirds of the replicates or with pooled replicates (P= 0.066). Consequently, we cannot recommend using leaf litter bags to index populations of northern two-lined salamanders.

A nondestructive technique to monitor the relative abundance of terrestrial salamanders

Treesearch

Richard M. DeGraaf; Mariko Yamasaki

1992-01-01

Salamanders are abundant vertebrates in many forest ecosystems, and their annual biomass production can be important in forest food webs (Pough et al. 1987). Population densities of eastern redback salamanders (Plethodon cinereus) can exceed 2 individuals/m2 in deciduous forests of the United States (Heatwole 1962, Jaeger 1980...

Recent introduction of a chytrid fungus endangers Western Palearctic salamanders

PubMed Central

Martel, A.; Beukema, W.; Fisher, M. C.; Farrer, R. A.; Schmidt, B. R.; Tobler, U.; Goka, K.; Lips, K. R.; Muletz, C.; Zamudio, K. R.; Bosch, J.; Lötters, S.; Wombwell, E.; Garner, T.W. J.; Cunningham, A. A.; Spitzen-van der Sluijs, A.; Salvidio, S.; Ducatelle, R.; Nishikawa, K.; Nguyen, T. T.; Kolby, J. E.; Van Bocxlaer, I.; Bossuyt, F.; Pasmans, F.

2018-01-01

Emerging infectious diseases are reducing biodiversity on a global scale. Recently, the emergence of the chytrid fungus Batrachochytrium salamandrivorans resulted in rapid declines in populations of European fire salamanders. Here, we screened more than 5000 amphibians from across four continents and combined experimental assessment of pathogenicity with phylogenetic methods to estimate the threat that this infection poses to amphibian diversity. Results show that B. salamandrivorans is restricted to, but highly pathogenic for, salamanders and newts (Urodela). The pathogen likely originated and remained in coexistence with a clade of salamander hosts for millions of years in Asia. As a result of globalization and lack of biosecurity, it has recently been introduced into naïve European amphibian populations, where it is currently causing biodiversity loss. PMID:25359973

Effects of microhabitat and land use on stream salamander abundance in the southwest Virginia coalfields

USGS Publications Warehouse

Sweeten, Sara E.; Ford, W. Mark

2015-01-01

Large-scale land uses such as residential wastewater discharge and coal mining practices, particularly surface coal extraction and associated valley fills, are of particular ecological concern in central Appalachia. Identification and quantification of both alterations across scales are a necessary first-step to mitigate negative consequences to biota. In central Appalachian headwater streams absent of fish, salamanders are the dominant, most abundant vertebrate predator providing a significant intermediate trophic role. Stream salamander species are considered to be sensitive to aquatic stressors and environmental alterations, and past research has shown linkages among microhabitat parameters, large-scale land use such as urbanization and logging with salamander abundances. However, little is known about these linkages in the coalfields of central Appalachia. In the summer of 2013, we visited 70 sites (sampled three times each) in the southwest Virginia coalfields to survey salamanders and quantify stream and riparian microhabitat parameters. Using an information-theoretic framework we compared the effects of microhabitat and large-scale land use on salamander abundances. Our findings indicate that dusky salamander (Desmognathus spp.) abundances are more correlated to microhabitat parameters such as canopy cover than to subwatershed land uses. Brook salamander (Eurycea spp.) abundances show strong negative associations to the suspended sediments and stream substrate embeddedness. Neither Desmognathus spp. nor Eurycea spp. abundances were influenced by water conductivity. These suggest protection or restoration of riparian habitats and erosion control is an important conservation component for maintaining stream salamanders in the mined landscapes of central Appalachia.

Successful gene therapy in the RPGRIP1-deficient dog: a large model of cone-rod dystrophy.

PubMed

Lhériteau, Elsa; Petit, Lolita; Weber, Michel; Le Meur, Guylène; Deschamps, Jack-Yves; Libeau, Lyse; Mendes-Madeira, Alexandra; Guihal, Caroline; François, Achille; Guyon, Richard; Provost, Nathalie; Lemoine, Françoise; Papal, Samantha; El-Amraoui, Aziz; Colle, Marie-Anne; Moullier, Philippe; Rolling, Fabienne

2014-02-01

For the development of new therapies, proof-of-concept studies in large animal models that share clinical features with their human counterparts represent a pivotal step. For inherited retinal dystrophies primarily involving photoreceptor cells, the efficacy of gene therapy has been demonstrated in canine models of stationary cone dystrophies and progressive rod-cone dystrophies but not in large models of progressive cone-rod dystrophies, another important cause of blindness. To address the last issue, we evaluated gene therapy in the retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1)-deficient dog, a model exhibiting a severe cone-rod dystrophy similar to that seen in humans. Subretinal injection of AAV5 (n = 5) or AAV8 (n = 2) encoding the canine Rpgrip1 improved photoreceptor survival in transduced areas of treated retinas. Cone function was significantly and stably rescued in all treated eyes (18-72% of those recorded in normal eyes) up to 24 months postinjection. Rod function was also preserved (22-29% of baseline function) in four of the five treated dogs up to 24 months postinjection. No detectable rod function remained in untreated contralateral eyes. More importantly, treatment preserved bright- and dim-light vision. Efficacy of gene therapy in this large animal model of cone-rod dystrophy provides great promise for human treatment.

[Retinal pigmentary degeneration--clinical features, diagnostics and possibilities of treatment].

PubMed

Grześk, Magdalena; Malukiewicz-Wiśniewska, Grazyna

2007-01-01

The purpose of this study was to evaluate clinical course of retinitis pigmentosa taking into consideration models of inheritance and possible treatment. Retinitis pigmentosa belongs to heterogeneous group of hereditary disorders, which are connected with gradual loss of the photoreceptor function, firstly rod cells subsequently cones, which is accompanied by the retinal pigmentary epithelium disorder. Retinitis pigmentosa connected with X chromosome is one of the most severe form of this disease that in polish population takes place with frequency at average 10-15% which is similar to ADRP--10-20%. Course of RP, despite many similarities may differ from each other and prognosis depends on model of inheritance. Unfortunately, in spite of many efforts, nowadays medicine do not have successful treatment for patients with RP.

Early Microglia Activation Precedes Photoreceptor Degeneration in a Mouse Model of CNGB1-Linked Retinitis Pigmentosa.

PubMed

Blank, Thomas; Goldmann, Tobias; Koch, Mirja; Amann, Lukas; Schön, Christian; Bonin, Michael; Pang, Shengru; Prinz, Marco; Burnet, Michael; Wagner, Johanna E; Biel, Martin; Michalakis, Stylianos

2017-01-01

Retinitis pigmentosa (RP) denotes a family of inherited blinding eye diseases characterized by progressive degeneration of rod and cone photoreceptors in the retina. In most cases, a rod-specific genetic defect results in early functional loss and degeneration of rods, which is followed by degeneration of cones and loss of daylight vision at later stages. Microglial cells, the immune cells of the central nervous system, are activated in retinas of RP patients and in several RP mouse models. However, it is still a matter of debate whether activated microglial cells may be responsible for the amplification of the typical degenerative processes. Here, we used Cngb1 -/- mice, which represent a slow degenerative mouse model of RP, to investigate the extent of microglia activation in retinal degeneration. With a combination of FACS analysis, immunohistochemistry and gene expression analysis we established that microglia in the Cngb1 -/- retina were already activated in an early, predegenerative stage of the disease. The evidence available so far suggests that early retinal microglia activation represents a first step in RP, which might initiate or accelerate photoreceptor degeneration.

Cannibalistic-morph Tiger Salamanders in unexpected ecological contexts

USGS Publications Warehouse

McLean, Kyle I.; Stockwell, Craig A.; Mushet, David M.

2016-01-01

Barred tiger salamanders [Ambystoma mavortium (Baird, 1850)] exhibit two trophic morphologies; a typical and a cannibalistic morph. Cannibalistic morphs, distinguished by enlarged vomerine teeth, wide heads, slender bodies, and cannibalistic tendencies, are often found where conspecifics occur at high density. During 2012 and 2013, 162 North Dakota wetlands and lakes were sampled for salamanders. Fifty-one contained A. mavortium populations; four of these contained cannibalistic morph individuals. Two populations with cannibalistic morphs occurred at sites with high abundances of conspecifics. However, the other two populations occurred at sites with unexpectedly low conspecific but high fathead minnow [Pimephales promelas (Rafinesque, 1820)] abundances. Further, no typical morphs were observed in either of these later two populations, contrasting with earlier research suggesting cannibalistic morphs only occur at low frequencies in salamander populations. Another anomaly of all four populations was the occurrence of cannibalistic morphs in permanent water sites, suggesting their presence was due to factors other than faster growth allowing them to occupy ephemeral habitats. Therefore, our findings suggest environmental factors inducing the cannibalistic morphism may be more complex than previously thought.

Olfactory Dysfunction in Patients With CNGB1-Associated Retinitis Pigmentosa.

PubMed

Charbel Issa, Peter; Reuter, Peggy; Kühlewein, Laura; Birtel, Johannes; Gliem, Martin; Tropitzsch, Anke; Whitcroft, Katherine L; Bolz, Hanno J; Ishihara, Kenji; MacLaren, Robert E; Downes, Susan M; Oishi, Akio; Zrenner, Eberhart; Kohl, Susanne; Hummel, Thomas

2018-05-24

Co-occurrence of retinitis pigmentosa (RP) and olfactory dysfunction may have a common genetic cause. To report olfactory function and the retinal phenotype in patients with biallelic mutations in CNGB1, a gene coding for a signal transduction channel subunit expressed in rod photoreceptors and olfactory sensory neurons. This case series was conducted from August 2015 through July 2017. The setting was a multicenter study involving 4 tertiary referral centers for inherited retinal dystrophies. Participants were 9 patients with CNGB1-associated RP. Results of olfactory testing, ocular phenotyping, and molecular genetic testing using targeted next-generation sequencing. Nine patients were included in the study, 3 of whom were female. Their ages ranged between 34 and 79 years. All patients had an early onset of night blindness but were usually not diagnosed as having RP before the fourth decade because of slow retinal degeneration. Retinal features were characteristic of a rod-cone dystrophy. Olfactory testing revealed reduced or absent olfactory function, with all except one patient scoring in the lowest quartile in relation to age-related norms. Brain magnetic resonance imaging and electroencephalography measurements in response to olfactory stimulation were available for 1 patient and revealed no visible olfactory bulbs and reduced responses to odor, respectively. Molecular genetic testing identified 5 novel (c.1312C>T, c.2210G>A, c.2492+1G>A, c.2763C>G, and c.3044_3050delGGAAATC) and 5 previously reported mutations in CNGB1. Mutations in CNGB1 may cause an autosomal recessive RP-olfactory dysfunction syndrome characterized by a slow progression of retinal degeneration and variable anosmia or hyposmia.

Overwintered Bullfrog tadpoles negatively affect Salamanders and Anurans in native amphibian communities

USGS Publications Warehouse

Boone, M.D.; Little, E.E.; Semlitsch, R.D.

2004-01-01

We examined the interactive effects of overwintered Bullfrog (Rana catesbeiana) tadpoles and pond hydroperiod on a community of larval amphibians in outdoor mesocosms including American Toads (Bufo americanus), Southern Leopard Frogs (Rana sphenocephala), and Spotted Salamanders (Ambystoma maculatum) - species within the native range of Bullfrogs. Spotted Salamanders and Southern Leopard Frogs were negatively influenced by the presence of overwintered Bullfrogs. Spotted Salamanders had shorter larval periods and slightly smaller masses at metamorphosis, and Southern Leopard Frogs had smaller masses at metamorphosis when reared with Bullfrogs than without. Presence of overwintered Bullfrogs, however, did not significantly affect American Toads. Longer pond hydroperiods resulted in greater survival, greater size at metamorphosis, longer larval periods, and later time until emergence of the first metamorphs for Southern Leopard Frog tadpoles and Spotted Salamander larvae. Our study demonstrated that overwintered Bullfrog tadpoles can respond to changing pond hydroperiods and can negatively impact metamorphosis of native amphibians.

Retinal pigment epithelial dystrophy in Briard dogs.

PubMed

Lightfoot, R M; Cabral, L; Gooch, L; Bedford, P G; Boulton, M E

1996-01-01

The eyes of normal Briard dogs, Briards affected with inherited retinal pigment epithelial dystrophy (RPED) and a range of normal crossbred and beagle dogs were examined and the histopathology of RPED in the Briard was compared with the histopathological features of ageing in the normal canine retina. RPED was characterised by the accumulation of auto-fluorescent lipofuscin-like inclusions in the retinal pigment epithelium (RPE), which initially involved only non-pigmented RPE cells overlying the tapetum but subsequently spread to all pigmented RPE cells. Secondary neuro-retinal degeneration was characterised by a gradual loss of the outer nuclear layer and the subsequent atrophy and degeneration of the inner retina. The loss of primary photoreceptors in the peripheral retina was accompanied by the migration of photoreceptor nuclei and appeared to resemble severe changes due to ageing. Intra-vitreal radiolabelled leucine was used to examine the rate of turnover of the outer segments of the rods in some Briards, but no significant variations were found. The activity of acid phosphatase in RPE was assayed in vitro and showed comparable regional variations in Briard and crossbred dogs. The results suggest that RPED in the Briard is unlikely to be due either to an increased rate of turnover of rod outer segments (and thus an increased phagocytic load) or to a primary insufficiency of lysosomal enzyme.

Influence of headwater site conditions and riparian buffers on terrestrial salamander response to forest thinning.

Treesearch

D.E. Rundio; D.H. Olson

2007-01-01

We examined the effect of forest thinning and riparian buffers along headwater streams on terrestrial salamanders at two sites in western Oregon. Salamander numbers were reduced postthinning at one site with lower down-wood volume. Terrestrial salamander distributions along stream-to-upslope transects suggest benefits of one and two site-potential tree-height stream...

Dramatic declines in neotropical salamander populations are an important part of the global amphibian crisis

PubMed Central

Rovito, Sean M.; Parra-Olea, Gabriela; Vásquez-Almazán, Carlos R.; Papenfuss, Theodore J.; Wake, David B.

2009-01-01

We document major declines of many species of salamanders at several sites in Central America and Mexico, with emphasis on the San Marcos region of Guatemala, one of the best studied and most diverse salamander communities in the Neotropics. Profound declines of several formerly abundant species, including 2 apparent extinctions, are revealed. Terrestrial microhabitat specialists at mid- to high elevations have declined more than microhabitat generalists. These terrestrial microhabitat specialists have largely disappeared from multiple sites in western Guatemala, including in well-protected areas, suggesting that the phenomenon cannot be explained solely by localized habitat destruction. Major declines in southern Mexican plethodontid salamanders occurred in the late 1970s to early 1980s, concurrent with or preceding many reported frog declines. The species in decline comprise several major evolutionary lineages of tropical salamanders, underscoring that significant portions of the phylogenetic diversity of Neotropical salamanders are at risk. Our results highlight the urgent need to document and understand Neotropical salamander declines as part of the larger effort to conserve global amphibian diversity. PMID:19204286

Mechanics of lung ventilation in a post-metamorphic salamander, Ambystoma Tigrinum.

PubMed

Simons, R S; Bennett, W O; Brainerd, E L

2000-03-01

The mechanics of lung ventilation in frogs and aquatic salamanders has been well characterized, whereas lung ventilation in terrestrial-phase (post-metamorphic) salamanders has received little attention. We used electromyography (EMG), X-ray videography, standard videography and buccal and body cavity pressure measurements to characterize the ventilation mechanics of adult (post-metamorphic) tiger salamanders (Ambystoma tigrinum). Three results emerged: (i) under terrestrial conditions or when floating at the surface of the water, adult A. tigrinum breathed through their nares using a two-stroke buccal pump; (ii) in addition to this narial two-stroke pump, adult tiger salamanders also gulped air in through their mouths using a modified two-stroke buccal pump when in an aquatic environment; and (iii) exhalation in adult tiger salamanders is active during aquatic gulping breaths, whereas exhalation appears to be passive during terrestrial breathing at rest. Active exhalation in aquatic breaths is indicated by an increase in body cavity pressure during exhalation and associated EMG activity in the lateral hypaxial musculature, particularly the M. transversus abdominis. In terrestrial breathing, no EMG activity in the lateral hypaxial muscles is generally present, and body cavity pressure decreases during exhalation. In aquatic breaths, tidal volume is larger than in terrestrial breaths, and breathing frequency is much lower (approximately 1 breath 10 min(-)(1 )versus 4-6 breaths min(-)(1)). The use of hypaxial muscles to power active exhalation in the aquatic environment may result from the need for more complete exhalation and larger tidal volumes when breathing infrequently. This hypothesis is supported by previous findings that terrestrial frogs ventilate their lungs with small tidal volumes and exhale passively, whereas aquatic frogs and salamanders use large tidal volumes and and exhale actively.

Spatial variation in water loss predicts terrestrial salamander distribution and population dynamics.

PubMed

Peterman, W E; Semlitsch, R D

2014-10-01

Many patterns observed in ecology, such as species richness, life history variation, habitat use, and distribution, have physiological underpinnings. For many ectothermic organisms, temperature relationships shape these patterns, but for terrestrial amphibians, water balance may supersede temperature as the most critical physiologically limiting factor. Many amphibian species have little resistance to water loss, which restricts them to moist microhabitats, and may significantly affect foraging, dispersal, and courtship. Using plaster models as surrogates for terrestrial plethodontid salamanders (Plethodon albagula), we measured water loss under ecologically relevant field conditions to estimate the duration of surface activity time across the landscape. Surface activity time was significantly affected by topography, solar exposure, canopy cover, maximum air temperature, and time since rain. Spatially, surface activity times were highest in ravine habitats and lowest on ridges. Surface activity time was a significant predictor of salamander abundance, as well as a predictor of successful recruitment; the probability of a juvenile salamander occupying an area with high surface activity time was two times greater than an area with limited predicted surface activity. Our results suggest that survival, recruitment, or both are demographic processes that are affected by water loss and the ability of salamanders to be surface-active. Results from our study extend our understanding of plethodontid salamander ecology, emphasize the limitations imposed by their unique physiology, and highlight the importance of water loss to spatial population dynamics. These findings are timely for understanding the effects that fluctuating temperature and moisture conditions predicted for future climates will have on plethodontid salamanders.

Ambystoma maculatum (spotted salamander). Reproduction

USGS Publications Warehouse

Glorioso, Brad M.; Waddle, Hardin; Hefner, Jeromi

2012-01-01

The Spotted Salamander is a wide-ranging salamander of the eastern United States that typically breeds in winter or early spring in ephemeral pools in lowland forests. Ambystoma maculatum is known to deposit 2-4 egg masses per year, each containing 1-250 eggs. As part of ongoing research into the ecology and reproductive biology of Spotted Salamanders in the Kisatchie District of Kisatchie National Forest in Natchitoches Parish, Louisiana, USA, we have been counting the number of embryos per egg mass. We captured seven female A. maculatum in a small pool, six of which were still gravid. We took standard measurements, including SVL, and then implanted a Passive Integrated Transponder (PIT tag) into each adult female as was the protocol. About an hour after processing these animals we marked new A. maculatum egg masses found in the same small pool using PVC pin flags pushed carefully through the outer jelly. We did not have enough time to process them that evening, and it was not until a few days later that we photographed those masses. We discovered that one of the masses contained a PIT tag in the outer jelly that corresponded to one of the six gravid females that were marked that same evening. To our knowledge, this is the first report of PIT tags being the means, albeit coincidentally, by which a particular egg mass of Ambystoma maculatum has been assigned to a particular female. For our purposes, losing the PIT tag from the adult female is counter to the goals of our study of this population, and we will no longer be implanting PIT tags into gravid females.

Detection of an enigmatic plethodontid Salamander using Environmental DNA

USGS Publications Warehouse

Pierson, Todd W.; Mckee, Anna; Spear, Stephen F.; Maerz, John C.; Camp, Carlos D.; Glenn, Travis C.

2016-01-01

The isolation and identification of environmental DNA (eDNA) offers a non-invasive and efficient method for the detection of rare and secretive aquatic wildlife, and it is being widely integrated into inventory and monitoring efforts. The Patch-Nosed Salamander (Urspelerpes brucei) is a tiny, recently discovered species of plethodontid salamander known only from headwater streams in a small region of Georgia and South Carolina. Here, we present results of a quantitative PCR-based eDNA assay capable of detecting Urspelerpes in more than 75% of 33 samples from five confirmed streams. We deployed the method at 31 additional streams and located three previously undocumented populations of Urspelerpes. We compare the results of our eDNA assay with our attempt to use aquatic leaf litterbags for the rapid detection of Urspelerpes and demonstrate the relative efficacy of the eDNA assay. We suggest that eDNA offers great potential for use in detecting other aquatic and semi-aquatic plethodontid salamanders.

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays.

PubMed

Light, Jacob G; Fransen, James W; Adekunle, Adewumi N; Adkins, Alice; Pangeni, Gobinda; Loudin, James; Mathieson, Keith; Palanker, Daniel V; McCall, Maureen A; Pardue, Machelle T

2014-11-01

Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6-12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16-26 weeks post-implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission. Published

Proinsulin slows retinal degeneration and vision loss in the P23H rat model of retinitis pigmentosa.

PubMed

Fernández-Sánchez, Laura; Lax, Pedro; Isiegas, Carolina; Ayuso, Eduard; Ruiz, José M; de la Villa, Pedro; Bosch, Fatima; de la Rosa, Enrique J; Cuenca, Nicolás

2012-12-01

Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin on photoreceptor degeneration, synaptic connectivity, and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H homozygous rats received an intramuscular injection of an adeno-associated viral vector serotype 1 (AAV1) expressing human proinsulin (hPi+) or AAV1-null vector (hPi-) at P20. Levels of hPi in serum were determined by enzyme-linked immunosorbent assay (ELISA), and visual function was evaluated by electroretinographic (ERG) recording at P30, P60, P90, and P120. Preservation of retinal structure was assessed by immunohistochemistry at P120. Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from 1.1 nM (P30) to 1.4 nM (P120). ERG recordings showed an amelioration of vision loss in hPi+ animals. The scotopic b-waves were significantly higher in hPi+ animals than in control rats at P90 and P120. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. hPi+ animals had 48.7% more photoreceptors than control animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in hPi+ P23H rats. Furthermore, in hPi+ rat retinas the number of rod bipolar cell bodies was greater than in control rats. Our data demonstrate that hPi expression preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in the P23H rat. These data strongly support the further development of proinsulin-based therapy to counteract retinitis pigmentosa.

Antifungal Bacteria on Woodland Salamander Skin Exhibit High Taxonomic Diversity and Geographic Variability

PubMed Central

DiRenzo, Graziella V.; Yarwood, Stephanie A.; Campbell Grant, Evan H.; Fleischer, Robert C.; Lips, Karen R.

2017-01-01

ABSTRACT Diverse bacteria inhabit amphibian skin; some of those bacteria inhibit growth of the fungal pathogen Batrachochytrium dendrobatidis. Yet there has been no systematic survey of anti-B. dendrobatidis bacteria across localities, species, and elevations. This is important given geographic and taxonomic variations in amphibian susceptibility to B. dendrobatidis. Our collection sites were at locations within the Appalachian Mountains where previous sampling had indicated low B. dendrobatidis prevalence. We determined the numbers and identities of anti-B. dendrobatidis bacteria on 61 Plethodon salamanders (37 P. cinereus, 15 P. glutinosus, 9 P. cylindraceus) via culturing methods and 16S rRNA gene sequencing. We sampled co-occurring species at three localities and sampled P. cinereus along an elevational gradient (700 to 1,000 meters above sea level [masl]) at one locality. We identified 50 anti-B. dendrobatidis bacterial operational taxonomic units (OTUs) and found that the degree of B. dendrobatidis inhibition was not correlated with relatedness. Five anti-B. dendrobatidis bacterial strains occurred on multiple amphibian species at multiple localities, but none were shared among all species and localities. The prevalence of anti-B. dendrobatidis bacteria was higher at Shenandoah National Park (NP), VA, with 96% (25/26) of salamanders hosting at least one anti-B. dendrobatidis bacterial species compared to 50% (7/14) at Catoctin Mountain Park (MP), MD, and 38% (8/21) at Mt. Rogers National Recreation Area (NRA), VA. At the individual level, salamanders at Shenandoah NP had more anti-B. dendrobatidis bacteria per individual (μ = 3.3) than those at Catoctin MP (μ = 0.8) and at Mt. Rogers NRA (μ = 0.4). All salamanders tested negative for B. dendrobatidis. Anti-B. dendrobatidis bacterial species are diverse in central Appalachian Plethodon salamanders, and their distribution varied geographically. The antifungal bacterial species that we identified may play a

Antifungal Bacteria on Woodland Salamander Skin Exhibit High Taxonomic Diversity and Geographic Variability.

PubMed

Muletz-Wolz, Carly R; DiRenzo, Graziella V; Yarwood, Stephanie A; Campbell Grant, Evan H; Fleischer, Robert C; Lips, Karen R

2017-05-01

Diverse bacteria inhabit amphibian skin; some of those bacteria inhibit growth of the fungal pathogen Batrachochytrium dendrobatidis Yet there has been no systematic survey of anti- B. dendrobatidis bacteria across localities, species, and elevations. This is important given geographic and taxonomic variations in amphibian susceptibility to B. dendrobatidis Our collection sites were at locations within the Appalachian Mountains where previous sampling had indicated low B. dendrobatidis prevalence. We determined the numbers and identities of anti- B. dendrobatidis bacteria on 61 Plethodon salamanders (37 P. cinereus , 15 P. glutinosus , 9 P. cylindraceus ) via culturing methods and 16S rRNA gene sequencing. We sampled co-occurring species at three localities and sampled P. cinereus along an elevational gradient (700 to 1,000 meters above sea level [masl]) at one locality. We identified 50 anti- B. dendrobatidis bacterial operational taxonomic units (OTUs) and found that the degree of B. dendrobatidis inhibition was not correlated with relatedness. Five anti- B. dendrobatidis bacterial strains occurred on multiple amphibian species at multiple localities, but none were shared among all species and localities. The prevalence of anti- B. dendrobatidis bacteria was higher at Shenandoah National Park (NP), VA, with 96% (25/26) of salamanders hosting at least one anti- B. dendrobatidis bacterial species compared to 50% (7/14) at Catoctin Mountain Park (MP), MD, and 38% (8/21) at Mt. Rogers National Recreation Area (NRA), VA. At the individual level, salamanders at Shenandoah NP had more anti- B. dendrobatidis bacteria per individual (μ = 3.3) than those at Catoctin MP (μ = 0.8) and at Mt. Rogers NRA (μ = 0.4). All salamanders tested negative for B. dendrobatidis Anti- B. dendrobatidis bacterial species are diverse in central Appalachian Plethodon salamanders, and their distribution varied geographically. The antifungal bacterial species that we identified may play a

Salamander abundance along road edges and within abandoned logging roads in Appalachian forests.

PubMed

Semlitsch, Raymond D; Ryan, Travis J; Hamed, Kevin; Chatfield, Matt; Drehman, Bethany; Pekarek, Nicole; Spath, Mike; Watland, Angie

2007-02-01

Roads may be one of the most common disturbances in otherwise continuous forested habitat in the southern Appalachian Mountains. Despite their obvious presence on the landscape, there is limited data on the ecological effects along a road edge or the size of the "road-effect zone." We sampled salamanders at current and abandoned road sites within the Nantahala National Forest, North Carolina (U.S.A.) to determine the road-effect zone for an assemblage of woodland salamanders. Salamander abundance near the road was reduced significantly, and salamanders along the edges were predominantly large individuals. These results indicate that the road-effect zone for these salamanders extended 35 m on either side of the relatively narrow, low-use forest roads along which we sampled. Furthermore, salamander abundance was significantly lower on old, abandoned logging roads compared with the adjacent upslope sites. These results indicate that forest roads and abandoned logging roads have negative effects on forest-dependent species such as plethodontid salamanders. Our results may apply to other protected forests in the southern Appalachians and may exemplify a problem created by current and past land use activities in all forested regions, especially those related to road building for natural-resource extraction. Our results show that the effect of roads reached well beyond their boundary and that abandonment or the decommissioning of roads did not reverse detrimental ecological effects; rather, our results indicate that management decisions have significant repercussions for generations to come. Furthermore, the quantity of suitable forested habitat in the protected areas we studied was significantly reduced: between 28.6% and 36.9% of the area was affected by roads. Management and policy decisions must use current and historical data on land use to understand cumulative impacts on forest-dependent species and to fully protect biodiversity on national lands.

Patients and animal models of CNGβ1-deficient retinitis pigmentosa support gene augmentation approach

PubMed Central

Petersen-Jones, Simon M.; Occelli, Laurence M.; Winkler, Paige A.; Lee, Winston; Sparrow, Janet R.; Tsukikawa, Mai; Boye, Sanford L.; Chiodo, Vince; Capasso, Jenina E.; Becirovic, Elvir; Schön, Christian; Seeliger, Mathias W.; Levin, Alex V.; Hauswirth, William W.

2017-01-01

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene augmentation using adeno-associated virus vectors robustly sustained the rescue of rod function and preserved retinal structure in the dog model. Together, our results reveal an early loss of rod function in CNGB1-deficient patients and a wide window for therapeutic intervention. Moreover, the identification of potential biomarkers of outcome measures, availability of relevant animal models, and robust functional rescue from gene augmentation therapy support future work to move CNGB1-RP therapies toward clinical trials. PMID:29202463

Retinal Structure Measurements as Inclusion Criteria for Stem Cell-Based Therapies of Retinal Degenerations.

PubMed

Jacobson, Samuel G; Matsui, Rodrigo; Sumaroka, Alexander; Cideciyan, Artur V

2016-04-01

We reviewed and illustrated the most optimal retinal structural measurements to make in stem cell clinical trials. Optical coherence tomography (OCT) and autofluorescence (AF) imaging were used to evaluate patients with severe visual loss from nonsyndromic and syndromic retinitis pigmentosa (RP), ABCA4-Stargardt disease, and nonneovascular age-related macular degeneration (AMD). Outer nuclear layer (ONL), rod outer segment (ROS) layer, inner retina, ganglion cell layer (GCL), and nerve fiber layer (NFL) thicknesses were quantified. All patients had severely reduced visual acuities. Retinitis pigmentosa patients had limited visual fields; maculopathy patients had central scotomas with retained peripheral function. For the forms of RP illustrated, there was detectable albeit severely reduced ONL across the scanned retina, and normal or hyperthick GCL and NFL. Maculopathy patients had no measurable ONL centrally; it became detectable with eccentricity. Some maculopathy patients showed unexpected GCL losses. Autofluorescence imaging illustrated central losses of RPE integrity. A hypothetical scheme to relate patient data with different phases of retinal remodeling in animal models of retinal degeneration was presented. Stem cell science is advancing, but it is not too early to open the discussion of criteria for patient selection and monitoring. Available clinical tools, such as OCT and AF imaging, can provide inclusion/exclusion criteria and robust objective outcomes. Accepting that early trials may not lead to miraculous cures, we should be prepared to know why-scientifically and clinically-so we can improve subsequent trials. We also must determine if retinal remodeling is an impediment to efficacy.

The Neural Circuit Mechanisms Underlying the Retinal Response to Motion Reversal

PubMed Central

Chen, Eric Y.; Chou, Janice; Park, Jeongsook; Schwartz, Greg

2014-01-01

To make up for delays in visual processing, retinal circuitry effectively predicts that a moving object will continue moving in a straight line, allowing retinal ganglion cells to anticipate the object's position. However, a sudden reversal of motion triggers a synchronous burst of firing from a large group of ganglion cells, possibly signaling a violation of the retina's motion prediction. To investigate the neural circuitry underlying this response, we used a combination of multielectrode array and whole-cell patch recordings to measure the responses of individual retinal ganglion cells in the tiger salamander to reversing stimuli. We found that different populations of ganglion cells were responsible for responding to the reversal of different kinds of objects, such as bright versus dark objects. Using pharmacology and designed stimuli, we concluded that ON and OFF bipolar cells both contributed to the reversal response, but that amacrine cells had, at best, a minor role. This allowed us to formulate an adaptive cascade model (ACM), similar to the one previously used to describe ganglion cell responses to motion onset. By incorporating the ON pathway into the ACM, we were able to reproduce the time-varying firing rate of fast OFF ganglion cells for all experimentally tested stimuli. Analysis of the ACM demonstrates that bipolar cell gain control is primarily responsible for generating the synchronized retinal response, as individual bipolar cells require a constant time delay before recovering from gain control. PMID:25411485

Estimation of stream salamander (Plethodontidae, Desmognathinae and Plethodontinae) populations in Shenandoah National Park, Virginia, USA

USGS Publications Warehouse

Jung, R.E.; Royle, J. Andrew; Sauer, J.R.; Addison, C.; Rau, R.D.; Shirk, J.L.; Whissel, J.C.

2005-01-01

Stream salamanders in the family Plethodontidae constitute a large biomass in and near headwater streams in the eastern United States and are promising indicators of stream ecosystem health. Many studies of stream salamanders have relied on population indices based on counts rather than population estimates based on techniques such as capture-recapture and removal. Application of estimation procedures allows the calculation of detection probabilities (the proportion of total animals present that are detected during a survey) and their associated sampling error, and may be essential for determining salamander population sizes and trends. In 1999, we conducted capture-recapture and removal population estimation methods for Desmognathus salamanders at six streams in Shenandoah National Park, Virginia, USA. Removal sampling appeared more efficient and detection probabilities from removal data were higher than those from capture-recapture. During 2001-2004, we used removal estimation at eight streams in the park to assess the usefulness of this technique for long-term monitoring of stream salamanders. Removal detection probabilities ranged from 0.39 to 0.96 for Desmognathus, 0.27 to 0.89 for Eurycea and 0.27 to 0.75 for northern spring (Gyrinophilus porphyriticus) and northern red (Pseudotriton ruber) salamanders across stream transects. Detection probabilities did not differ across years for Desmognathus and Eurycea, but did differ among streams for Desmognathus. Population estimates of Desmognathus decreased between 2001-2002 and 2003-2004 which may be related to changes in stream flow conditions. Removal-based procedures may be a feasible approach for population estimation of salamanders, but field methods should be designed to meet the assumptions of the sampling procedures. New approaches to estimating stream salamander populations are discussed.

Two R7 RGS proteins shape retinal bipolar cell signaling

PubMed Central

Mojumder, Deb Kumar; Qian, Yan; Wensel, Theodore G.

2009-01-01

RGS7, RGS11, and their binding partner Gβ5 are localized to the dendritic tips of retinal ON bipolar cells (ON-BPC), where mGluR6 responds to glutamate released from photoreceptor terminals by activation of the RGS7/RGS11 substrate, Gαo. To determine their functions in retinal signaling, we investigated cell-specific expression patterns of RGS7 and RGS11 by immunostaining, and measured light responses by electroretinography (ERG) in mice with targeted disruptions of the genes encoding them. RGS7 staining is present in dendritic tips of all rod ON-BPC, but missing in those for subsets of cone ON-BPC, whereas the converse was true for RGS11 staining. Genetic disruption of either RGS7 or RGS11 produced delays in the ON-BPC-derived electroretinogram b-wave, but no changes in the photoreceptor-derived a-wave. Homozygous RGS7 mutant mice had delays in rod-driven b-waves, whereas, RGS11 mutant mice had delays in rod-driven, and especially in cone-driven b-waves. The b-wave delays were further enhanced in mice homozygous for both RGS7 and RGS11 gene disruptions. Thus, RGS7 and RGS11 act in parallel to regulate the kinetics of ON bipolar cell responses, with differential impacts on the rod and cone pathways. PMID:19535587

Design tradeoffs in long-term research for stream salamanders

USGS Publications Warehouse

Brand, Adrianne B,; Grant, Evan H. Campbell

2017-01-01

Long-term research programs can benefit from early and periodic evaluation of their ability to meet stated objectives. In particular, consideration of the spatial allocation of effort is key. We sampled 4 species of stream salamanders intensively for 2 years (2010–2011) in the Chesapeake and Ohio Canal National Historical Park, Maryland, USA to evaluate alternative distributions of sampling locations within stream networks, and then evaluated via simulation the ability of multiple survey designs to detect declines in occupancy and to estimate dynamic parameters (colonization, extinction) over 5 years for 2 species. We expected that fine-scale microhabitat variables (e.g., cobble, detritus) would be the strongest determinants of occupancy for each of the 4 species; however, we found greater support for all species for models including variables describing position within the stream network, stream size, or stream microhabitat. A monitoring design focused on headwater sections had greater power to detect changes in occupancy and the dynamic parameters in each of 3 scenarios for the dusky salamander (Desmognathus fuscus) and red salamander (Pseudotriton ruber). Results for transect length were more variable, but across all species and scenarios, 25-m transects are most suitable as a balance between maximizing detection probability and describing colonization and extinction. These results inform sampling design and provide a general framework for setting appropriate goals, effort, and duration in the initial planning stages of research programs on stream salamanders in the eastern United States.

The Effects of Diabetic Retinopathy and Pan-Retinal Photocoagulation on Photoreceptor Cell Function as Assessed by Dark Adaptometry

PubMed Central

Bavinger, J. Clay; Dunbar, Grace E.; Stem, Maxwell S.; Blachley, Taylor S.; Kwark, Leon; Farsiu, Sina; Jackson, Gregory R.; Gardner, Thomas W.

2016-01-01

Purpose The pathophysiology of vision loss in persons with diabetic retinopathy (DR) is complex and incompletely defined. We hypothesized that retinal pigment epithelium (RPE) and rod and cone photoreceptor dysfunction, as measured by dark adaptometry, would increase with severity of DR, and that pan-retinal photocoagulation (PRP) would exacerbate this dysfunction. Methods Dark adaptation (DA) was measured in subjects with diabetes mellitus and healthy controls. Dark adaptation was measured at 5° superior to the fovea following a flash bleach, and the data were analyzed to yield cone and rod sensitivity curves. Retinal layer thicknesses were quantified using spectral-domain optical coherence tomography (OCT). Results The sample consisted of 23 controls and 73 diabetic subjects. Subjects with moderate nonproliferative diabetic retinopathy (NPDR) exhibited significant impairment of rod recovery rate compared with control subjects (P = 0.04). Cone sensitivity was impaired in subjects with proliferative diabetic retinopathy (PDR) (type 1 diabetes mellitus [T1DM]: P = 0.0047; type 2 diabetes mellitus [T2DM]: P < 0.001). Subjects with untreated PDR compared with subjects treated with PRP exhibited similar rod recovery rates and cone sensitivities. Thinner RPE as assessed by OCT was associated with slower rod recovery and lower cone sensitivity, and thinner photoreceptor inner segment/outer segment layer was associated with lower cone sensitivity. Conclusions The results suggest that RPE and photoreceptor cell dysfunction, as assessed by cone sensitivity level and rod- and RPE-mediated dark adaptation, progresses with worsening DR, and rod recovery dysfunction occurs earlier than cone dysfunction. Function was preserved following PRP. The findings suggest multiple defects in retinoid function and provide potential points to improve visual function in persons with PDR. PMID:26803796

Genetic drift and mutational hazard in the evolution of salamander genomic gigantism.

PubMed

Mohlhenrich, Erik Roger; Mueller, Rachel Lockridge

2016-12-01

Salamanders have the largest nuclear genomes among tetrapods and, excepting lungfishes, among vertebrates as a whole. Lynch and Conery (2003) have proposed the mutational-hazard hypothesis to explain variation in genome size and complexity. Under this hypothesis, noncoding DNA imposes a selective cost by increasing the target for degenerative mutations (i.e., the mutational hazard). Expansion of noncoding DNA, and thus genome size, is driven by increased levels of genetic drift and/or decreased mutation rates; the former determines the efficiency with which purifying selection can remove excess DNA, whereas the latter determines the level of mutational hazard. Here, we test the hypothesis that salamanders have experienced stronger long-term, persistent genetic drift than frogs, a related clade with more typically sized vertebrate genomes. To test this hypothesis, we compared dN/dS and Kr/Kc values of protein-coding genes between these clades. Our results do not support this hypothesis; we find that salamanders have not experienced stronger genetic drift than frogs. Additionally, we find evidence consistent with a lower nucleotide substitution rate in salamanders. This result, along with previous work showing lower rates of small deletion and ectopic recombination in salamanders, suggests that a lower mutational hazard may contribute to genomic gigantism in this clade. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Methodological considerations for detection of terrestrial small-body salamander eDNA and implications for biodiversity conservation

USGS Publications Warehouse

Walker, Donald M.; Leys, Jacob E.; Dunham, Kelly E.; Oliver, Joshua C.; Schiller, Emily E.; Stephenson, Kelsey S.; Kimrey, John T.; Wooten, Jessica; Rogers, Mark W.

2017-01-01

Environmental DNA (eDNA) can be used as an assessment tool to detect populations of threatened species and provide fine-scale data required to make management decisions. The objectives of this project were to use quantitative PCR (qPCR) to: (i) detect spiked salamander DNA in soil, (ii) quantify eDNA degradation over time, (iii) determine detectability of salamander eDNA in a terrestrial environment using soil, faeces, and skin swabs, (iv) detect salamander eDNA in a mesocosm experiment. Salamander eDNA was positively detected in 100% of skin swabs and 66% of faecal samples and concentrations did not differ between the two sources. However, eDNA was not detected in soil samples collected from directly underneath wild-caught living salamanders. Salamander genomic DNA (gDNA) was detected in all qPCR reactions when spiked into soil at 10.0, 5.0, and 1.0 ng/g soil and spike concentration had a significant effect on detected concentrations. Only 33% of samples showed recoverable eDNA when spiked with 0.25 ng/g soil, which was the low end of eDNA detection. To determine the rate of eDNA degradation, gDNA (1 ng/g soil) was spiked into soil and quantified over seven days. Salamander eDNA concentrations decreased across days, but eDNA was still amplifiable at day 7. Salamander eDNA was detected in two of 182 mesocosm soil samples over 12 weeks (n = 52 control samples; n = 65 presence samples; n = 65 eviction samples). The discrepancy in detection success between experiments indicates the potential challenges for this method to be used as a monitoring technique for small-bodied wild terrestrial salamander populations.

Methodological considerations for detection of terrestrial small-body salamander eDNA and implications for biodiversity conservation.

PubMed

Walker, Donald M; Leys, Jacob E; Dunham, Kelly E; Oliver, Joshua C; Schiller, Emily E; Stephenson, Kelsey S; Kimrey, John T; Wooten, Jessica; Rogers, Mark W

2017-11-01

Environmental DNA (eDNA) can be used as an assessment tool to detect populations of threatened species and provide fine-scale data required to make management decisions. The objectives of this project were to use quantitative PCR (qPCR) to: (i) detect spiked salamander DNA in soil, (ii) quantify eDNA degradation over time, (iii) determine detectability of salamander eDNA in a terrestrial environment using soil, faeces, and skin swabs, (iv) detect salamander eDNA in a mesocosm experiment. Salamander eDNA was positively detected in 100% of skin swabs and 66% of faecal samples and concentrations did not differ between the two sources. However, eDNA was not detected in soil samples collected from directly underneath wild-caught living salamanders. Salamander genomic DNA (gDNA) was detected in all qPCR reactions when spiked into soil at 10.0, 5.0, and 1.0 ng/g soil and spike concentration had a significant effect on detected concentrations. Only 33% of samples showed recoverable eDNA when spiked with 0.25 ng/g soil, which was the low end of eDNA detection. To determine the rate of eDNA degradation, gDNA (1 ng/g soil) was spiked into soil and quantified over seven days. Salamander eDNA concentrations decreased across days, but eDNA was still amplifiable at day 7. Salamander eDNA was detected in two of 182 mesocosm soil samples over 12 weeks (n = 52 control samples; n = 65 presence samples; n = 65 eviction samples). The discrepancy in detection success between experiments indicates the potential challenges for this method to be used as a monitoring technique for small-bodied wild terrestrial salamander populations. © 2017 John Wiley & Sons Ltd.

76 FR 44036 - Proposed Low-Effect Habitat Conservation Plan for the California Tiger Salamander, AT&T Portable...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-22

...] Proposed Low-Effect Habitat Conservation Plan for the California Tiger Salamander, AT&T Portable Generator... Federally listed animal, the California tiger salamander. The applicant would implement a conservation... permanently convert 1.24 acres of upland grassland habitat for the California tiger salamander into a new...

Mercury bioaccumulation in northern two-lined salamanders from streams in the northeastern United States

USGS Publications Warehouse

Bank, M.S.; Loftin, C.S.; Jung, R.E.

2005-01-01

Mercury (Hg) bioaccumulation in salamanders has received little attention despite widespread Hg contamination of aquatic ecosystems and worldwide amphibian declines. Here we report concentrations of methyl Hg (MeHg) and total Hg in larval northern two-lined salamanders (Eurycea bislineata bislineata) collected from streams in Acadia National Park (ANP), Maine, and Bear Brook Watershed, Maine (BBWM; a paired, gauged watershed treated with bimonthly applications (25 kg/ha/yr) of ammonium sulfate [(NH4)(2)SO4]) since 1989), and Shenandoah National Park (SNP), Virginia. MeHg comprised 73-97% of total Hg in the larval salamander composite samples from ANP. At BBWM we detected significantly higher total Hg levels in larvae from the (NH4)(2)SO4 treatment watershed. At ANP total Hg concentrations in salamander larvae were significantly higher from streams in unburned watersheds in contrast with larval samples collected from streams located in watersheds burned by the 1947 Bar Harbor fire. Additionally, total Hg levels were significantly higher in salamander larvae collected at ANP in contrast with SNP. Our results suggest that watershed-scale attributes including. re history, whole-catchment (NH4)(2)SO4 additions, wetland extent, and forest cover type influence mercury bioaccumulation in salamanders inhabiting lotic environments. We also discuss the use of this species as an indicator of Hg bioaccumulation in stream ecosystems.

Do silvicultural practices to restore oaks affect salamanders in the short term?

Treesearch

Amy L. Raybuck; Christopher E. Moorman; Sarah R. Fritts; Cathryn H. Greenberg; Christopher S. Deperno; Dean M. Simon; Gordon S. Warburton

2015-01-01

Salamanders are an important ecological component of eastern hardwood forests and may be affected by natural or silvicultural disturbances that alter habitat structure and associated microclimate. From May to August in 2008 (pre- treatment) and 2011 (post-treatment), we evaluated the response of salamanders to three silvicultural practices designed to promote oak...

Rapid Retinal Release from a Cone Visual Pigment Following Photoactivation*

PubMed Central

Chen, Min-Hsuan; Kuemmel, Colleen; Birge, Robert R.; Knox, Barry E.

2012-01-01

As part of the visual cycle, the retinal chromophore in both rod and cone visual pigments undergoes reversible Schiff base hydrolysis and dissociation following photobleaching. We characterized light-activated retinal release from a short-wavelength sensitive cone pigment (VCOP) in 0.1% dodecyl maltoside using fluorescence spectroscopy. The half-time (t1/2) of retinal release from VCOP was 7.1 s, 250-fold faster than rhodopsin. VCOP exhibited pH-dependent release kinetics, with the t1/2 decreasing from 23 s to 4 s with pH 4.1 to 8, respectively. However, the Arrhenius activation energy (Ea) for VCOP derived from kinetic measurements between 4° and 20°C was 17.4 kcal/mol, similar to 18.5 kcal/mol for rhodopsin. There was a small kinetic isotope (D2O) effect in VCOP, but less than that observed in rhodopsin. Mutation of the primary Schiff base counterion (VCOPD108A) produced a pigment with an unprotonated chromophore (⌊max = 360 nm) and dramatically slowed (t1/2 ~ 6.8 min) light-dependent retinal release. Using homology modeling, a VCOP mutant with two substitutions (S85D/ D108A) was designed to move the counterion one alpha helical turn into the transmembrane region from the native position. This double mutant had a UV-visible absorption spectrum consistent with a protonated Schiff base (⌊max = 420 nm). Moreover, VCOPS85D/D108A mutant had retinal release kinetics (t1/2 = 7 s) and Ea (18 kcal/mol) similar to the native pigment exhibiting no pH-dependence. By contrast, the single mutant VCOPS85D had a ~3-fold decrease in retinal release rate compared to the native pigment. Photoactivated VCOPD108A had kinetics comparable to a rhodopsin counterion mutant, RhoE113Q, both requiring hydroxylamine to fully release retinal. These results demonstrate that the primary counterion of cone visual pigments is necessary for efficient Schiff base hydrolysis. We discuss how the large differences in retinal release rates between rod and cone visual pigments arise, not from

Retinal Laminar Architecture in Human Retinitis Pigmentosa Caused by Rhodopsin Gene Mutations

PubMed Central

Aleman, Tomas S.; Cideciyan, Artur V.; Sumaroka, Alexander; Windsor, Elizabeth A. M.; Herrera, Waldo; White, D. Alan; Kaushal, Shalesh; Naidu, Anjani; Roman, Alejandro J.; Schwartz, Sharon B.; Stone, Edwin M.; Jacobson, Samuel G.

2008-01-01

Purpose. To determine the underlying retinal micropathology in subclasses of autosomal dominant retinitis pigmentosa (ADRP) caused by rhodopsin (RHO) mutations. Methods. Patients with RHO-ADRP (n = 17, ages 6–73 years), representing class A (R135W and P347L) and class B (P23H, T58R, and G106R) functional phenotypes, were studied with optical coherence tomography (OCT), and colocalized visual thresholds were determined by dark- and light-adapted chromatic perimetry. Autofluorescence imaging was performed with near-infrared light. Retinal histology in hT17M-rhodopsin mice was compared with the human results. Results. Class A patients had only cone-mediated vision. The outer nuclear layer (ONL) thinned with eccentricity and was not detectable within 3 to 4 mm of the fovea. Scotomatous extracentral retina showed loss of ONL, thickening of the inner retina, and demelanization of RPE. Class B patients had superior–inferior asymmetry in function and structure. The superior retina could have normal rod and cone vision, normal lamination (including ONL) and autofluorescence of the RPE melanin; laminopathy was found in the scotomas. With Fourier-domain-OCT, there was apparent inner nuclear layer (INL) thickening in regions with ONL thinning. Retinal regions without ONL had a thick hyporeflective layer that was continuous with the INL from neighboring regions with normal lamination. Transgenic mice had many of the laminar abnormalities found in patients. Conclusions. Retinal laminar abnormalities were present in both classes of RHO-ADRP and were related to the severity of colocalized vision loss. The results in human class B and the transgenic mice support the following disease sequence: ONL diminution with INL thickening; amalgamation of residual ONL with the thickened INL; and progressive retinal remodeling with eventual thinning. PMID:18385078

Melanopsin Phototransduction Contributes to Light-Evoked Choroidal Expansion and Rod L-Type Calcium Channel Function In Vivo.

PubMed

Berkowitz, Bruce A; Schmidt, Tiffany; Podolsky, Robert H; Roberts, Robin

2016-10-01

In humans, rodents, and pigeons, the dark → light transition signals nonretinal brain tissue to increase choroidal thickness, a major control element of choroidal blood flow, and thus of photoreceptor and retinal pigment epithelium function. However, it is unclear which photopigments in the retina relay the light signal to the brain. Here, we test the hypothesis that melanopsin (Opn4)-regulated phototransduction modulates light-evoked choroidal thickness expansion in mice. Two-month-old C57Bl/6 wild-type (B6), 4- to 5-month-old C57Bl/6/129S6 wild-type (B6 + S6), and 2-month-old melanopsin knockout (Opn4-/-) on a B6 + S6 background were studied. Retinal anatomy was evaluated in vivo by optical coherence tomography and MRI. Choroidal thickness in dark and light were measured by diffusion-weighted MRI. Rod cell L-type calcium channel (LTCC) function in dark and light (manganese-enhanced MRI [MEMRI]) was also measured. Opn4-/- mice did not show the light-evoked expansion of choroidal thickness observed in B6 and B6 + S6 controls. Additionally, Opn4-/- mice had lower than normal rod cell and inner retinal LTCC function in the dark but not in the light. These deficits were not due to structural abnormalities because retinal laminar architecture and thickness, and choroidal thickness in the Opn4-/- mice were similar to controls. First time evidence is provided that melanopsin phototransduction contributes to dark → light control of murine choroidal thickness. The data also highlight a contribution in vivo of melanopsin phototransduction to rod cell and inner retinal depolarization in the dark.

New Wrinkles in Retinal Densitometry

PubMed Central

Masella, Benjamin D.; Hunter, Jennifer J.; Williams, David R.

2014-01-01

Purpose. Retinal densitometry provides objective information about retinal function. But, a number of factors, including retinal reflectance changes that are not directly related to photopigment depletion, complicate its interpretation. We explore these factors and suggest a method to minimize their impact. Methods. An adaptive optics scanning light ophthalmoscope (AOSLO) was used to measure changes in photoreceptor reflectance in monkeys before and after photopigment bleaching with 514-nm light. Reflectance measurements at 514 nm and 794 nm were recorded simultaneously. Several methods of normalization to extract the apparent optical density of the photopigment were compared. Results. We identified stimulus-related fluctuations in 794-nm reflectance that are not associated with photopigment absorptance and occur in both rods and cones. These changes had a magnitude approaching those associated directly with pigment depletion, precluding the use of infrared reflectance for normalization. We used a spatial normalization method instead, which avoided the fluctuations in the near infrared, as well as a confocal AOSLO designed to minimize light from layers other than the receptors. However, these methods produced a surprisingly low estimate of the apparent rhodopsin density (animal 1: 0.073 ± 0.006, animal 2: 0.032 ± 0.003). Conclusions. These results confirm earlier observations that changes in photopigment absorption are not the only source of retinal reflectance change during dark adaptation. It appears that the stray light that has historically reduced the apparent density of cone photopigment in retinal densitometry arises predominantly from layers near the photoreceptors themselves. Despite these complications, this method provides a valuable, objective measure of retinal function. PMID:25316726

A novel homozygous truncating GNAT1 mutation implicated in retinal degeneration.

PubMed

Carrigan, Matthew; Duignan, Emma; Humphries, Pete; Palfi, Arpad; Kenna, Paul F; Farrar, G Jane

2016-04-01

The GNAT1 gene encodes the α subunit of the rod transducin protein, a key element in the rod phototransduction cascade. Variants in GNAT1 have been implicated in stationary night-blindness in the past, but unlike other proteins in the same pathway, it has not previously been implicated in retinitis pigmentosa. A panel of 182 retinopathy-associated genes was sequenced to locate disease-causing mutations in patients with inherited retinopathies. Sequencing revealed a novel homozygous truncating mutation in the GNAT1 gene in a patient with significant pigmentary disturbance and constriction of visual fields, a presentation consistent with retinitis pigmentosa. This is the first report of a patient homozygous for a complete loss-of-function GNAT1 mutation. The clinical data from this patient provide definitive evidence of retinitis pigmentosa with late onset in addition to the lifelong night-blindness that would be expected from a lack of transducin function. These data suggest that some truncating GNAT1 variants can indeed cause a recessive, mild, late-onset retinal degeneration in human beings rather than just stationary night-blindness as reported previously, with notable similarities to the phenotype of the Gnat1 knockout mouse. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Contributions of Rod and Cone Pathways to Retinal Direction Selectivity Through Development

PubMed Central

Rosa, Juliana M.; Morrie, Ryan D.; Baertsch, Hans C.

2016-01-01

Direction selectivity is a robust computation across a broad stimulus space that is mediated by activity of both rod and cone photoreceptors through the ON and OFF pathways. However, rods, S-cones, and M-cones activate the ON and OFF circuits via distinct pathways and the relative contribution of each to direction selectivity is unknown. Using a variety of stimulation paradigms, pharmacological agents, and knockout mice that lack rod transduction, we found that inputs from the ON pathway were critical for strong direction-selective (DS) tuning in the OFF pathway. For UV light stimulation, the ON pathway inputs to the OFF pathway originated with rod signaling, whereas for visible stimulation, the ON pathway inputs to the OFF pathway originated with both rod and M-cone signaling. Whole-cell voltage-clamp recordings revealed that blocking the ON pathway reduced directional tuning in the OFF pathway via a reduction in null-side inhibition, which is provided by OFF starburst amacrine cells (SACs). Consistent with this, our recordings from OFF SACs confirmed that signals originating in the ON pathway contribute to their excitation. Finally, we observed that, for UV stimulation, ON contributions to OFF DS tuning matured earlier than direct signaling via the OFF pathway. These data indicate that the retina uses multiple strategies for computing DS responses across different colors and stages of development. SIGNIFICANCE STATEMENT The retina uses parallel pathways to encode different features of the visual scene. In some cases, these distinct pathways converge on circuits that mediate a distinct computation. For example, rod and cone pathways enable direction-selective (DS) ganglion cells to encode motion over a wide range of light intensities. Here, we show that although direction selectivity is robust across light intensities, motion discrimination for OFF signals is dependent upon ON signaling. At eye opening, ON directional tuning is mature, whereas OFF DS tuning is

Predicted changes in climatic niche and climate refugia of conservation priority salamander species in the northeastern United States

USGS Publications Warehouse

Sutton, William B.; Barrett, Kyle; Moody, Allison T.; Loftin, Cynthia S.; deMaynadier, Phillip G.; Nanjappa, Priya

2015-01-01

Global climate change represents one of the most extensive and pervasive threats to wildlife populations. Amphibians, specifically salamanders, are particularly susceptible to the effects of changing climates due to their restrictive physiological requirements and low vagility; however, little is known about which landscapes and species are vulnerable to climate change. Our study objectives included, (1) evaluating species-specific predictions (based on 2050 climate projections) and vulnerabilities to climate change and (2) using collective species responses to identify areas of climate refugia for conservation priority salamanders in the northeastern United States. All evaluated salamander species were projected to lose a portion of their climatic niche. Averaged projected losses ranged from 3%–100% for individual species, with the Cow Knob Salamander (Plethodon punctatus), Cheat Mountain Salamander (Plethodon nettingi), Shenandoah Mountain Salamander (Plethodon virginia), Mabee’s Salamander (Ambystoma mabeei), and Streamside Salamander (Ambystoma barbouri) predicted to lose at least 97% of their landscape-scale climatic niche. The Western Allegheny Plateau was predicted to lose the greatest salamander climate refugia richness (i.e., number of species with a climatically-suitable niche in a landscape patch), whereas the Central Appalachians provided refugia for the greatest number of species during current and projected climate scenarios. Our results can be used to identify species and landscapes that are likely to be further affected by climate change and potentially resilient habitats that will provide consistent climatic conditions in the face of environmental change.

A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration.

PubMed

Chavali, Venkata R M; Khan, Naheed W; Cukras, Catherine A; Bartsch, Dirk-Uwe; Jablonski, Monica M; Ayyagari, Radha

2011-05-15

Late-onset retinal macular degeneration (L-ORD) is an autosomal dominant inherited disorder caused by a single missense mutation (S163R) in the CTRP5/C1QTNF5 protein. Early phenotypic features of L-ORD include: dark adaptation abnormalities, nyctalopia, and drusen deposits in the peripheral macular region. Apart from posterior segment abnormalities, these patients also develop abnormally long anterior lens zonules. In the sixth decade of life the rod and cone function declines, accompanied by electroretinogram (ERG) abnormalities. Some patients also develop choroidal neovascularization and glaucoma. In order to understand the disease pathology and mechanisms involved in retinal dystrophy, we generated a knock-in (Ctrp5(+/-)) mouse model carrying the disease-associated mutation in the mouse Ctrp5/C1QTNF5 gene. These mice develop slower rod-b wave recovery consistent with early dark adaptation abnormalities, accumulation of hyperautofluorescence spots, retinal pigment epithelium abnormalities, drusen, Bruch's membrane abnormalities, loss of photoreceptors, and retinal vascular leakage. The Ctrp5(+/-) mice, which have most of the pathological features of age-related macular degeneration, are unique and may serve as a valuable model both to understand the molecular pathology of late-onset retinal degeneration and to evaluate therapies.

AAV-mediated Gene Therapy Halts Retinal Degeneration in PDE6β-deficient Dogs

PubMed Central

Pichard, Virginie; Provost, Nathalie; Mendes-Madeira, Alexandra; Libeau, Lyse; Hulin, Philippe; Tshilenge, Kizito-Tshitoko; Biget, Marine; Ameline, Baptiste; Deschamps, Jack-Yves; Weber, Michel; Le Meur, Guylène; Colle, Marie-Anne; Moullier, Philippe; Rolling, Fabienne

2016-01-01

We previously reported that subretinal injection of AAV2/5 RK.cpde6β allowed long-term preservation of photoreceptor function and vision in the rod-cone dysplasia type 1 (rcd1) dog, a large animal model of naturally occurring PDE6β deficiency. The present study builds on these earlier findings to provide a detailed assessment of the long-term effects of gene therapy on the spatiotemporal pattern of retinal degeneration in rcd1 dogs treated at 20 days of age. We analyzed the density distribution of the retinal layers and of particular photoreceptor cells in 3.5-year-old treated and untreated rcd1 dogs. Whereas no rods were observed outside the bleb or in untreated eyes, gene transfer halted rod degeneration in all vector-exposed regions. Moreover, while gene therapy resulted in the preservation of cones, glial cells and both the inner nuclear and ganglion cell layers, no cells remained in vector-unexposed retinas, except in the visual streak. Finally, the retinal structure of treated 3.5-year-old rcd1 dogs was identical to that of unaffected 4-month-old rcd1 dogs, indicating near complete preservation. Our findings indicate that gene therapy arrests the degenerative process even if intervention is initiated after the onset of photoreceptor degeneration, and point to significant potential of this therapeutic approach in future clinical trials. PMID:26857842

AAV-mediated Gene Therapy Halts Retinal Degeneration in PDE6β-deficient Dogs.

PubMed

Pichard, Virginie; Provost, Nathalie; Mendes-Madeira, Alexandra; Libeau, Lyse; Hulin, Philippe; Tshilenge, Kizito-Tshitoko; Biget, Marine; Ameline, Baptiste; Deschamps, Jack-Yves; Weber, Michel; Le Meur, Guylène; Colle, Marie-Anne; Moullier, Philippe; Rolling, Fabienne

2016-05-01

We previously reported that subretinal injection of AAV2/5 RK.cpde6β allowed long-term preservation of photoreceptor function and vision in the rod-cone dysplasia type 1 (rcd1) dog, a large animal model of naturally occurring PDE6β deficiency. The present study builds on these earlier findings to provide a detailed assessment of the long-term effects of gene therapy on the spatiotemporal pattern of retinal degeneration in rcd1 dogs treated at 20 days of age. We analyzed the density distribution of the retinal layers and of particular photoreceptor cells in 3.5-year-old treated and untreated rcd1 dogs. Whereas no rods were observed outside the bleb or in untreated eyes, gene transfer halted rod degeneration in all vector-exposed regions. Moreover, while gene therapy resulted in the preservation of cones, glial cells and both the inner nuclear and ganglion cell layers, no cells remained in vector-unexposed retinas, except in the visual streak. Finally, the retinal structure of treated 3.5-year-old rcd1 dogs was identical to that of unaffected 4-month-old rcd1 dogs, indicating near complete preservation. Our findings indicate that gene therapy arrests the degenerative process even if intervention is initiated after the onset of photoreceptor degeneration, and point to significant potential of this therapeutic approach in future clinical trials.

The Abundance of Salamanders in Forest Stands with Different Histories of Disturbance

Treesearch

F. Harvey Pough; Donald H. Rhodes; Andres Collazo

1987-01-01

Because of the importance of salamanders in forest food chains, the effects of forest management practices on populations of these animals warrant consideration. We compared the numbers and activity patterns of salamanders in areas of a deciduous forest in central New York State that had been cut selectively for firewood, or c1earcut, or planted with conifers. Numbers...

Primate Short-Wavelength Cones Share Molecular Markers with Rods

PubMed Central

Craft, Cheryl M.; Huang, Jing; Possin, Daniel E.; Hendrickson, Anita

2015-01-01

Macaca, Callithrix jacchus marmoset monkey, Pan troglodytes chim- panzee and human retinas were examined to define if short wavelength (S) cones share molecular markers with L&M cone or rod photoreceptors. S cones showed consistent differences in their immunohistochemical staining and expression levels compared to L&M cones for “rod” Arrestin1 (S-Antigen), “cone” Arrestin4, cone alpha transducin, and Calbindin. Our data verify a similar pattern of expression in these primate retinas and provide clues to the structural divergence of rods and S cones versus L&M cones, suggesting S cone retinal function is “intermediate” between them. PMID:24664680

℮-conome: an automated tissue counting platform of cone photoreceptors for rodent models of retinitis pigmentosa.

PubMed

Clérin, Emmanuelle; Wicker, Nicolas; Mohand-Saïd, Saddek; Poch, Olivier; Sahel, José-Alain; Léveillard, Thierry

2011-12-20

Retinitis pigmentosa is characterized by the sequential loss of rod and cone photoreceptors. The preservation of cones would prevent blindness due to their essential role in human vision. Rod-derived Cone Viability Factor is a thioredoxin-like protein that is secreted by rods and is involved in cone survival. To validate the activity of Rod-derived Cone Viability Factors (RdCVFs) as therapeutic agents for treating retinitis Pigmentosa, we have developed e-conome, an automated cell counting platform for retinal flat mounts of rodent models of cone degeneration. This automated quantification method allows for faster data analysis thereby accelerating translational research. An inverted fluorescent microscope, motorized and coupled to a CCD camera records images of cones labeled with fluorescent peanut agglutinin lectin on flat-mounted retinas. In an average of 300 fields per retina, nine Z-planes at magnification X40 are acquired after two-stage autofocus individually for each field. The projection of the stack of 9 images is subject to a threshold, filtered to exclude aberrant images based on preset variables. The cones are identified by treating the resulting image using 13 variables empirically determined. The cone density is calculated over the 300 fields. The method was validated by comparison to the conventional stereological counting. The decrease in cone density in rd1 mouse was found to be equivalent to the decrease determined by stereological counting. We also studied the spatiotemporal pattern of the degeneration of cones in the rd1 mouse and show that while the reduction in cone density starts in the central part of the retina, cone degeneration progresses at the same speed over the whole retinal surface. We finally show that for mice with an inactivation of the Nucleoredoxin-like genes Nxnl1 or Nxnl2 encoding RdCVFs, the loss of cones is more pronounced in the ventral retina. The automated platform ℮-conome used here for retinal disease is a tool that

Apparent predation by Gray Jays, Perisoreus canadensis, on Long-toed Salamanders, Ambystoma macrodactylum, in the Oregon Cascade Range

USGS Publications Warehouse

Murray, M.P.; Pearl, C.A.; Bury, R.B.

2005-01-01

We report observations of Gray Jays (Perisoreus canadensis) appearing to consume larval Long-toed Salamanders (Ambystoma macrodactylum) in a drying subalpine pond in Oregon, USA. Corvids are known to prey upon a variety of anuran amphibians, but to our knowledge, this is the first report of predation by any corvid on aquatic salamanders. Long-toed Salamanders appear palatable to Gray Jays, and may provide a food resource to Gray Jays when salamander larvae are concentrated in drying temporary ponds.

Retinal and visual system: occupational and environmental toxicology.

PubMed

Fox, Donald A

2015-01-01

Occupational chemical exposure often results in sensory systems alterations that occur without other clinical signs or symptoms. Approximately 3000 chemicals are toxic to the retina and central visual system. Their dysfunction can have immediate, long-term, and delayed effects on mental health, physical health, and performance and lead to increased occupational injuries. The aims of this chapter are fourfold. First, provide references on retinal/visual system structure, function, and assessment techniques. Second, discuss the retinal features that make it especially vulnerable to toxic chemicals. Third, review the clinical and corresponding experimental data regarding retinal/visual system deficits produced by occupational toxicants: organic solvents (carbon disulfide, trichloroethylene, tetrachloroethylene, styrene, toluene, and mixtures) and metals (inorganic lead, methyl mercury, and mercury vapor). Fourth, discuss occupational and environmental toxicants as risk factors for late-onset retinal diseases and degeneration. Overall, the toxicants altered color vision, rod- and/or cone-mediated electroretinograms, visual fields, spatial contrast sensitivity, and/or retinal thickness. The findings elucidate the importance of conducting multimodal noninvasive clinical, electrophysiologic, imaging and vision testing to monitor toxicant-exposed workers for possible retinal/visual system alterations. Finally, since the retina is a window into the brain, an increased awareness and understanding of retinal/visual system dysfunction should provide additional insight into acquired neurodegenerative disorders. © 2015 Elsevier B.V. All rights reserved.

Effects of edge contrast on redback salamander distribution in even-aged northern hardwoods

Treesearch

Richard M. DeGraaf; Mariko Yamasaki

2002-01-01

Terrestrial salamanders are sensitive to forest disturbance associated with even-aged management. We studied the distribution of redback salamanders (Plethodon cinereus) for 4 yr at edges between even-aged northern hardwood stands along three replicate transects in each of three edge contrast types: regeneration/mature, sapling/mature, and...

Long-term partial cutting impacts on Desmognathus salamander abundance in West Virginia headwater streams

Treesearch

Kurtis R. Moseley; W. Mark Ford; Thomas M. Schuler

2008-01-01

To understand long-term impacts of partial cutting practices on stream-dwelling salamanders in the central Appalachians, we examined pooled abundance of Desmognathus fuscus and D. monticola salamanders (hereafter Desmognathus) in headwater streams located within long-term silvicultural research compartments on...

Müller glia: Stem cells for generation and regeneration of retinal neurons in teleost fish

PubMed Central

Lenkowski, Jenny R.; Raymond, Pamela A.

2014-01-01

Adult zebrafish generate new neurons in the brain and retina throughout life. Growth-related neurogenesis allows a vigorous regenerative response to damage, and fish can regenerate retinal neurons, including photoreceptors, and restore functional vision following photic, chemical, or mechanical destruction of the retina. Müller glial cells in fish function as radial-glial-like neural stem cells. During adult growth, Müller glial nuclei undergo sporadic, asymmetric, self-renewing mitotic divisions in the inner nuclear layer to generate a rod progenitor that migrates along the radial fiber of the Müller glia into the outer nuclear layer, proliferates, and differentiates exclusively into rod photoreceptors. When retinal neurons are destroyed, Müller glia in the immediate vicinity of the damage partially and transiently dedifferentiate, re-express retinal progenitor and stem cell markers, re-enter the cell cycle, undergo interkinetic nuclear migration (characteristic of neuroepithelial cells), and divide once in an asymmetric, self-renewing division to generate a retinal progenitor. This daughter cell proliferates rapidly to form a compact neurogenic cluster surrounding the Müller glia; these multipotent retinal progenitors then migrate along the radial fiber to the appropriate lamina to replace missing retinal neurons. Some aspects of the injury-response in fish Müller glia resemble gliosis as observed in mammals, and mammalian Müller glia exhibit some neurogenic properties, indicative of a latent ability to regenerate retinal neurons. Understanding the specific properties of fish Müller glia that facilitate their robust capacity to generate retinal neurons will inform and inspire new clinical approaches for treating blindness and visual loss with regenerative medicine. PMID:24412518

Anatomy, function, and evolution of jaw and hyobranchial muscles in cryptobranchoid salamander larvae.

PubMed

Kleinteich, Thomas; Herzen, Julia; Beckmann, Felix; Matsui, Masafumi; Haas, Alexander

2014-02-01

Larval salamanders (Lissamphibia: Caudata) are known to be effective suction feeders in their aquatic environments, although they will eventually transform into terrestrial tongue feeding adults during metamorphosis. Early tetrapods may have had a similar biphasic life cycle and this makes larval salamanders a particularly interesting model to study the anatomy, function, development, and evolution of the feeding apparatus in terrestrial vertebrates. Here, we provide a description of the muscles that are involved in the feeding strike in salamander larvae of the Hynobiidae and compare them to larvae of the paedomorphic Cryptobranchidae. We provide a functional and evolutionary interpretation for the observed muscle characters. The cranial muscles in larvae from species of the Hynobiidae and Cryptobranchidae are generally very similar. Most notable are the differences in the presence of the m. hyomandibularis, a muscle that connects the hyobranchial apparatus with the lower jaw. We found this muscle only in Onychodactylus japonicus (Hynobiidae) but not in other hynobiid or cryptobranchid salamanders. Interestingly, the m. hyomandibularis in O. japonicus originates from the ceratobranchial I and not the ceratohyal, and thus exhibits what was previously assumed to be the derived condition. Finally, we applied a biomechanical model to simulate suction feeding in larval salamanders. We provide evidence that a flattened shape of the hyobranchial apparatus in its resting position is beneficial for a fast and successful suction feeding strike. Copyright © 2013 Wiley Periodicals, Inc.

Larval long-toed salamanders incur nonconsumptive effects in the presence of nonnative trout

USGS Publications Warehouse

Kenison, Erin K.; Litt, Andrea R.; Pilliod, David S.; McMahon, Thomas E.

2016-01-01

Predators can influence prey directly through consumption or indirectly through nonconsumptive effects (NCEs) by altering prey behavior, morphology, and life history. We investigated whether predator-avoidance behaviors by larval long-toed salamanders (Ambystoma macrodactylum) in lakes with nonnative trout result in NCEs on morphology and development. Field studies in lakes with and without trout were corroborated by experimental enclosures, where prey were exposed only to visual and chemical cues of predators. We found that salamanders in lakes with trout were consistently smaller than in lakes without trout: 38% lower weight, 24% shorter body length, and 29% shorter tail length. Similarly, salamanders in protective enclosures grew 2.9 times slower when exposed to visual and olfactory trout cues than when no trout cues were present. Salamanders in trout-free lakes and enclosures were 22.7 times and 1.48 times, respectively, more likely to metamorphose during the summer season than those exposed to trout in lakes and/or their cues. Observed changes in larval growth rate and development likely resulted from a facultative response to predator-avoidance behavior and demonstrate NCEs occurred even when predation risk was only perceived. Reduced body size and growth, as well as delayed metamorphosis, could have ecological consequences for salamander populations existing with fish if those effects carry-over into lower recruitment, survival, and fecundity.

Generation of three-dimensional retinal organoids expressing rhodopsin and S- and M-cone opsins from mouse stem cells.

PubMed

Ueda, Kaori; Onishi, Akishi; Ito, Shin-Ichiro; Nakamura, Makoto; Takahashi, Masayo

2018-01-22

Three-dimensional retinal organoids can be differentiated from embryonic stem cells/induced pluripotent stem cells (ES/iPS cells) under defined medium conditions. We modified the serum-free floating culture of embryoid body-like aggregates with quick reaggregation (SFEBq) culture procedure to obtain retinal organoids expressing more rod photoreceptors and S- and M-cone opsins. Retinal organoids differentiated from mouse Nrl-eGFP iPS cells were cultured in various mediums during photoreceptor development. To promote rod photoreceptor development, organoids were maintained in media containing 9-cis retinoic acids (9cRA). To obtain retinal organoids with M-opsin expression, we cultured in medium with 1% fetal bovine serum (FBS) supplemented with T3, BMP4, and DAPT. Section immunohistochemistry was performed to visualize the expression of photoreceptor markers. In three-dimensional (3D) retinas exposed to 9cRA, rhodopsin was expressed earlier and S-cone opsins were suppressed. We could maintain 3D retinas up to DD 35 in culture media with 1% FBS. The 3D retinas expressed rhodopsin, S- and M-opsins, but most cone photoreceptors expressed either S- or M-opsins. By modifying culture conditions in the SFEBq protocol, we obtained rod-dominated 3D retinas and S- and M-opsin expressing 3D retinas. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibitory masking controls the threshold sensitivity of retinal ganglion cells

PubMed Central

Pan, Feng; Toychiev, Abduqodir; Zhang, Yi; Atlasz, Tamas; Ramakrishnan, Hariharasubramanian; Roy, Kaushambi; Völgyi, Béla; Akopian, Abram

2016-01-01

Key points Retinal ganglion cells (RGCs) in dark‐adapted retinas show a range of threshold sensitivities spanning ∼3 log units of illuminance.Here, we show that the different threshold sensitivities of RGCs reflect an inhibitory mechanism that masks inputs from certain rod pathways.The masking inhibition is subserved by GABAC receptors, probably on bipolar cell axon terminals.The GABAergic masking inhibition appears independent of dopaminergic circuitry that has been shown also to affect RGC sensitivity.The results indicate a novel mechanism whereby inhibition controls the sensitivity of different cohorts of RGCs. This can limit and thereby ensure that appropriate signals are carried centrally in scotopic conditions when sensitivity rather than acuity is crucial. Abstract The responses of rod photoreceptors, which subserve dim light vision, are carried through the retina by three independent pathways. These pathways carry signals with largely different sensitivities. Retinal ganglion cells (RGCs), the output neurons of the retina, show a wide range of sensitivities in the same dark‐adapted conditions, suggesting a divergence of the rod pathways. However, this organization is not supported by the known synaptic morphology of the retina. Here, we tested an alternative idea that the rod pathways converge onto single RGCs, but inhibitory circuits selectively mask signals so that one pathway predominates. Indeed, we found that application of GABA receptor blockers increased the sensitivity of most RGCs by unmasking rod signals, which were suppressed. Our results indicate that inhibition controls the threshold responses of RGCs under dim ambient light. This mechanism can ensure that appropriate signals cross the bottleneck of the optic nerve in changing stimulus conditions. PMID:27350405

Decadal changes in phenology of peak abundance patterns of woodland pond salamanders in northern Wisconsin

USGS Publications Warehouse

Donner, Deahn M.; Ribic, Christine; Beck, Albert J.; Higgins, Dale; Eklund, Dan; Reinecke, Susan

2015-01-01

Woodland ponds are important landscape features that help sustain populations of amphibians that require this aquatic habitat for successful reproduction. Species abundance patterns often reflect site-specific differences in hydrology, physical characteristics, and surrounding vegetation. Large-scale processes such as changing land cover and environmental conditions are other potential drivers influencing amphibian populations in the Upper Midwest, but little information exists on the combined effects of these factors. We used Blue-spotted (Ambystoma laterale Hallowell) and Spotted Salamander (A. maculatum Shaw) monitoring data collected at the same woodland ponds thirteen years apart to determine if changing environmental conditions and vegetation cover in surrounding landscapes influenced salamander movement phenology and abundance. Four woodland ponds in northern Wisconsin were sampled for salamanders in April 1992-1994 and 2005-2007. While Blue-spotted Salamanders were more abundant than Spotted Salamanders in all ponds, there was no change in the numbers of either species over the years. However, peak numbers of Blue-spotted Salamanders occurred 11.7 days earlier (range: 9-14 days) in the 2000s compared to the 1990s; Spotted Salamanders occurred 9.5 days earlier (range: 3 - 13 days). Air and water temperatures (April 13- 24) increased, on average, 4.8°C and 3.7°C, respectively, between the decades regardless of pond. There were no discernible changes in canopy openness in surrounding forests between decades that would have warmed the water sooner (i.e., more light penetration). Our finding that salamander breeding phenology can vary by roughly 10 days in Wisconsin contributes to growing evidence that amphibian populations have responded to changing climate conditions by shifting life-cycle events. Managers can use this information to adjust monitoring programs and forest management activities in the surrounding landscape to avoid vulnerable amphibian

Successful Gene Therapy in the RPGRIP1-deficient Dog: a Large Model of Cone–Rod Dystrophy

PubMed Central

Lhériteau, Elsa; Petit, Lolita; Weber, Michel; Le Meur, Guylène; Deschamps, Jack-Yves; Libeau, Lyse; Mendes-Madeira, Alexandra; Guihal, Caroline; François, Achille; Guyon, Richard; Provost, Nathalie; Lemoine, Françoise; Papal, Samantha; El-Amraoui, Aziz; Colle, Marie-Anne; Moullier, Philippe; Rolling, Fabienne

2014-01-01

For the development of new therapies, proof-of-concept studies in large animal models that share clinical features with their human counterparts represent a pivotal step. For inherited retinal dystrophies primarily involving photoreceptor cells, the efficacy of gene therapy has been demonstrated in canine models of stationary cone dystrophies and progressive rod–cone dystrophies but not in large models of progressive cone–rod dystrophies, another important cause of blindness. To address the last issue, we evaluated gene therapy in the retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1)-deficient dog, a model exhibiting a severe cone–rod dystrophy similar to that seen in humans. Subretinal injection of AAV5 (n = 5) or AAV8 (n = 2) encoding the canine Rpgrip1 improved photoreceptor survival in transduced areas of treated retinas. Cone function was significantly and stably rescued in all treated eyes (18–72% of those recorded in normal eyes) up to 24 months postinjection. Rod function was also preserved (22–29% of baseline function) in four of the five treated dogs up to 24 months postinjection. No detectable rod function remained in untreated contralateral eyes. More importantly, treatment preserved bright- and dim-light vision. Efficacy of gene therapy in this large animal model of cone–rod dystrophy provides great promise for human treatment. PMID:24091916

Aneides ferreus (clouded salamander): arboreal activity

Treesearch

William W. Price; Clinton P. Landon; Eric D. Forsman

2010-01-01

Aneides ferreus (clouded salamander) inhabits the forests of western Oregon and extreme northwestern California. Although thought to be primarily terrestrial, A. ferreus has occasionally been found as high as 60 m up in trees and two recent reports suggest that it may be more arboreal than previously believed. However, it is...

On the ecological role of salamanders

Treesearch

Robert D. Davic; Hartwell H. Welsh Jr.

2004-01-01

Salamanders are cryptic and, though largely unrecognized as such, extremely abundant vertebrates in a variety of primarily forest and grassland environments, where they regulate food webs and contribute to ecosystem resilience-resistance (= stability) in several ways: (a) As mid-level vertebrate predators, they provide direct and indirect biotic control of species...

Spatiotemporal regulation of ATP and Ca2+ dynamics in vertebrate rod and cone ribbon synapses

PubMed Central

Johnson, Jerry E.; Perkins, Guy A.; Giddabasappa, Anand; Chaney, Shawntay; Xiao, Weimin; White, Andrew D.; Brown, Joshua M.; Waggoner, Jenna; Ellisman, Mark H.

2007-01-01

Purpose In conventional neurons, Ca2+ enters presynaptic terminals during an action potential and its increased local concentration triggers transient exocytosis. In contrast, vertebrate photoreceptors are nonspiking neurons that maintain sustained depolarization and neurotransmitter release from ribbon synapses in darkness and produce light-dependent graded hyperpolarizing responses. Rods transmit single photon responses with high fidelity, whereas cones are less sensitive and exhibit faster response kinetics. These differences are likely due to variations in presynaptic Ca2+ dynamics. Metabolic coupling and cross-talk between mitochondria, endoplasmic reticulum (ER), plasma membrane Ca2+ ATPase (PMCA), and Na+-Ca2+ exchanger (NCX) coordinately control presynaptic ATP production and Ca2+ dynamics. The goal of our structural and functional studies was to determine the spatiotemporal regulation of ATP and Ca2+ dynamics in rod spherules and cone pedicles. Methods Central retina tissue from C57BL/6 mice was used. Laser scanning confocal microscopy (LSCM) experiments were conducted on fixed-frozen vertical sections. Primary antibodies were selected for their tissue/cellular specificity and ability to recognize single, multiple or all splice variants of selected isoforms. Electron microscopy (EM) and 3-D electron tomography (ET) studies used our standard procedures on thin- and thick-sectioned retinas, respectively. Calibrated fluo-3-Ca2+ imaging experiments of dark- and light-adapted rod and cone terminals in retinal slices were conducted. Results Confocal microscopy showed that mitochondria, ER, PMCA, and NCX1 exhibited distinct retinal lamination patterns and differential distribution in photoreceptor synapses. Antibodies for three distinct mitochondrial compartments differentially labeled retinal areas with high metabolic demand: rod and cone inner segments, previously undescribed cone juxtanuclear mitochondria and the two plexiform layers. Rod spherule membranes

Spatiotemporal regulation of ATP and Ca2+ dynamics in vertebrate rod and cone ribbon synapses.

PubMed

Johnson, Jerry E; Perkins, Guy A; Giddabasappa, Anand; Chaney, Shawntay; Xiao, Weimin; White, Andrew D; Brown, Joshua M; Waggoner, Jenna; Ellisman, Mark H; Fox, Donald A

2007-06-15

In conventional neurons, Ca2+ enters presynaptic terminals during an action potential and its increased local concentration triggers transient exocytosis. In contrast, vertebrate photoreceptors are nonspiking neurons that maintain sustained depolarization and neurotransmitter release from ribbon synapses in darkness and produce light-dependent graded hyperpolarizing responses. Rods transmit single photon responses with high fidelity, whereas cones are less sensitive and exhibit faster response kinetics. These differences are likely due to variations in presynaptic Ca2+ dynamics. Metabolic coupling and cross-talk between mitochondria, endoplasmic reticulum (ER), plasma membrane Ca2+ ATPase (PMCA), and Na+-Ca2+ exchanger (NCX) coordinately control presynaptic ATP production and Ca2+ dynamics. The goal of our structural and functional studies was to determine the spatiotemporal regulation of ATP and Ca2+ dynamics in rod spherules and cone pedicles. Central retina tissue from C57BL/6 mice was used. Laser scanning confocal microscopy (LSCM) experiments were conducted on fixed-frozen vertical sections. Primary antibodies were selected for their tissue/cellular specificity and ability to recognize single, multiple or all splice variants of selected isoforms. Electron microscopy (EM) and 3-D electron tomography (ET) studies used our standard procedures on thin- and thick-sectioned retinas, respectively. Calibrated fluo-3-Ca2+ imaging experiments of dark- and light-adapted rod and cone terminals in retinal slices were conducted. Confocal microscopy showed that mitochondria, ER, PMCA, and NCX1 exhibited distinct retinal lamination patterns and differential distribution in photoreceptor synapses. Antibodies for three distinct mitochondrial compartments differentially labeled retinal areas with high metabolic demand: rod and cone inner segments, previously undescribed cone juxtanuclear mitochondria and the two plexiform layers. Rod spherule membranes uniformly and intensely

Adaptive optics retinal imaging: emerging clinical applications.

PubMed

Godara, Pooja; Dubis, Adam M; Roorda, Austin; Duncan, Jacque L; Carroll, Joseph

2010-12-01

The human retina is a uniquely accessible tissue. Tools like scanning laser ophthalmoscopy and spectral domain-optical coherence tomography provide clinicians with remarkably clear pictures of the living retina. Although the anterior optics of the eye permit such non-invasive visualization of the retina and associated pathology, the same optics induce significant aberrations that obviate cellular-resolution imaging in most cases. Adaptive optics (AO) imaging systems use active optical elements to compensate for aberrations in the optical path between the object and the camera. When applied to the human eye, AO allows direct visualization of individual rod and cone photoreceptor cells, retinal pigment epithelium cells, and white blood cells. AO imaging has changed the way vision scientists and ophthalmologists see the retina, helping to clarify our understanding of retinal structure, function, and the etiology of various retinal pathologies. Here, we review some of the advances that were made possible with AO imaging of the human retina and discuss applications and future prospects for clinical imaging.

The rod-driven a-wave of the dark-adapted mammalian electroretinogram.

PubMed

Robson, John G; Frishman, Laura J

2014-03-01

The a-wave of the electroretinogram (ERG) reflects the response of photoreceptors to light, but what determines the exact waveform of the recorded voltage is not entirely understood. We have now simulated the trans-retinal voltage generated by the photocurrent of dark-adapted mammalian rods, using an electrical model based on the in vitro measurements of Hagins et al. (1970) and Arden (1976) in rat retinas. Our simulations indicate that in addition to the voltage produced by extracellular flow of photocurrent from rod outer to inner segments, a substantial fraction of the recorded a-wave is generated by current that flows in the outer nuclear layer (ONL) to hyperpolarize the rod axon and synaptic terminal. This current includes a transient capacitive component that contributes an initial negative "nose" to the trans-retinal voltage when the stimulus is strong. Recordings in various species of the a-wave, including the peak and initial recovery towards the baseline, are consistent with simulations showing an initial transient primarily related to capacitive currents in the ONL. Existence of these capacitive currents can explain why there is always a substantial residual transient a-wave when post-receptoral responses are pharmacologically inactivated in rodents and nonhuman primates, or severely genetically compromised in humans (e.g. complete congenital stationary night blindness) and nob mice. Our simulations and analysis of ERGs indicate that the timing of the leading edge and peak of dark-adapted a-waves evoked by strong stimuli could be used in a simple way to estimate rod sensitivity. Copyright © 2013 Elsevier Ltd. All rights reserved.

A key role for cyclic nucleotide gated (CNG) channels in cGMP-related retinitis pigmentosa.

PubMed

Paquet-Durand, François; Beck, Susanne; Michalakis, Stylianos; Goldmann, Tobias; Huber, Gesine; Mühlfriedel, Regine; Trifunović, Dragana; Fischer, M Dominik; Fahl, Edda; Duetsch, Gabriele; Becirovic, Elvir; Wolfrum, Uwe; van Veen, Theo; Biel, Martin; Tanimoto, Naoyuki; Seeliger, Mathias W

2011-03-01

The rd1 natural mutant is one of the first and probably the most commonly studied mouse model for retinitis pigmentosa (RP), a severe and frequently blinding human retinal degeneration. In several decades of research, the link between the increase in photoreceptor cGMP levels and the extremely rapid cell death gave rise to a number of hypotheses. Here, we provide clear evidence that the presence of cyclic nucleotide gated (CNG) channels in the outer segment membrane is the key to rod photoreceptor loss. In Cngb1(-/-) × rd1 double mutants devoid of regular CNG channels, cGMP levels are still pathologically high, but rod photoreceptor viability and outer segment morphology are greatly improved. Importantly, cone photoreceptors, the basis for high-resolution daylight and colour vision, survived and remained functional for extended periods of time. These findings strongly support the hypothesis of deleterious calcium (Ca(2+))-influx as the cause of rapid rod cell death and highlight the importance of CNG channels in this process. Furthermore, our findings suggest that targeting rod CNG channels, rather than general Ca(2+)-channel blockade, is a most promising symptomatic approach to treat otherwise incurable forms of cGMP-related RP.

Rod Monochromacy and the Coevolution of Cetacean Retinal Opsins

PubMed Central

Meredith, Robert W.; Gatesy, John; Emerling, Christopher A.; York, Vincent M.; Springer, Mark S.

2013-01-01

Cetaceans have a long history of commitment to a fully aquatic lifestyle that extends back to the Eocene. Extant species have evolved a spectacular array of adaptations in conjunction with their deployment into a diverse array of aquatic habitats. Sensory systems are among those that have experienced radical transformations in the evolutionary history of this clade. In the case of vision, previous studies have demonstrated important changes in the genes encoding rod opsin (RH1), short-wavelength sensitive opsin 1 (SWS1), and long-wavelength sensitive opsin (LWS) in selected cetaceans, but have not examined the full complement of opsin genes across the complete range of cetacean families. Here, we report protein-coding sequences for RH1 and both color opsin genes (SWS1, LWS) from representatives of all extant cetacean families. We examine competing hypotheses pertaining to the timing of blue shifts in RH1 relative to SWS1 inactivation in the early history of Cetacea, and we test the hypothesis that some cetaceans are rod monochomats. Molecular evolutionary analyses contradict the “coastal” hypothesis, wherein SWS1 was pseudogenized in the common ancestor of Cetacea, and instead suggest that RH1 was blue-shifted in the common ancestor of Cetacea before SWS1 was independently knocked out in baleen whales (Mysticeti) and in toothed whales (Odontoceti). Further, molecular evidence implies that LWS was inactivated convergently on at least five occasions in Cetacea: (1) Balaenidae (bowhead and right whales), (2) Balaenopteroidea (rorquals plus gray whale), (3) Mesoplodon bidens (Sowerby's beaked whale), (4) Physeter macrocephalus (giant sperm whale), and (5) Kogia breviceps (pygmy sperm whale). All of these cetaceans are known to dive to depths of at least 100 m where the underwater light field is dim and dominated by blue light. The knockout of both SWS1 and LWS in multiple cetacean lineages renders these taxa rod monochromats, a condition previously unknown among

Acquired retinal pigmentary degeneration in a child with 13q deletion syndrome.

PubMed

Aguilera, Zenia P; Belin, Peter J; Cavuoto, Kara M; Jayakar, Parul; McKeown, Craig A

2015-10-01

Orbeli syndrome, or 13q deletion syndrome, is a rare condition caused by a distal deletion in the long arm of chromosome 13. The syndrome is characterized by severe physical malformations and developmental delays and has been associated with numerous ocular manifestations. We report the case of a 10-year-old boy with 13q deletion syndrome, who was evaluated for impaired vision and found to have bilateral retinal pigmentary changes resembling those seen in retinitis pigmentosa. There has only been one other case of retinal pigment variation in association with 13q deletion syndrome; however, this represents the first case of bilateral symmetric retinal pigmentary changes with corresponding rod and cone dysfunction on electroretinography. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Antifungal bacteria on woodland salamander skin exhibit high taxonomic diversity and geographic variability

USGS Publications Warehouse

Muletz-Wolz, Carly R.; DiRenzo, Graziella V.; Yarwood, Stephanie A.; Grant, Evan H. Campbell; Fleischer, Robert C.; Lips, Karen R.

2017-01-01

Diverse bacteria inhabit amphibian skin; some of those bacteria inhibit growth of the fungal pathogen Batrachochytrium dendrobatidis. Yet there has been no systematic survey of anti-B. dendrobatidis bacteria across localities, species, and elevations. This is important given geographic and taxonomic variations in amphibian susceptibility to B. dendrobatidis. Our collection sites were at locations within the Appalachian Mountains where previous sampling had indicated low B. dendrobatidis prevalence. We determined the numbers and identities of anti-B. dendrobatidis bacteria on 61 Plethodon salamanders (37 P. cinereus, 15 P. glutinosus, 9 P. cylindraceus) via culturing methods and 16S rRNA gene sequencing. We sampled co-occurring species at three localities and sampled P. cinereus along an elevational gradient (700 to 1,000 meters above sea level [masl]) at one locality. We identified 50 anti-B. dendrobatidis bacterial operational taxonomic units (OTUs) and found that the degree of B. dendrobatidis inhibition was not correlated with relatedness. Five anti-B. dendrobatidis bacterial strains occurred on multiple amphibian species at multiple localities, but none were shared among all species and localities. The prevalence of anti-B. dendrobatidis bacteria was higher at Shenandoah National Park (NP), VA, with 96% (25/26) of salamanders hosting at least one anti-B. dendrobatidis bacterial species compared to 50% (7/14) at Catoctin Mountain Park (MP), MD, and 38% (8/21) at Mt. Rogers National Recreation Area (NRA), VA. At the individual level, salamanders at Shenandoah NP had more anti-B. dendrobatidis bacteria per individual (μ = 3.3) than those at Catoctin MP (μ = 0.8) and at Mt. Rogers NRA (μ = 0.4). All salamanders tested negative for B. dendrobatidis. Anti-B. dendrobatidis bacterial species are diverse in central Appalachian Plethodon salamanders, and their distribution varied geographically. The antifungal bacterial species that we identified may play a protective

Survey of Pathogenic Chytrid Fungi (Batrachochytrium dendrobatidis and B. salamandrivorans) in Salamanders from Three Mountain Ranges in Europe and the Americas.

PubMed

Parrott, Joshua Curtis; Shepack, Alexander; Burkart, David; LaBumbard, Brandon; Scimè, Patrick; Baruch, Ethan; Catenazzi, Alessandro

2017-06-01

Batrachochytrium salamandrivorans (Bsal) is a virulent fungal pathogen that infects salamanders. It is implicated in the recent collapse of several populations of fire salamanders in Europe. This pathogen seems much like that of its sister species, Batrachochytrium dendrobatidis (Bd), the agent responsible for anuran extinctions and extirpations worldwide, and is considered to be an emerging global threat to salamander communities. Bsal thrives at temperatures found in many mountainous regions rich in salamander species; because of this, we have screened specimens of salamanders representing 17 species inhabiting mountain ranges in three continents: The Smoky Mountains, the Swiss Alps, and the Peruvian Andes. We screened 509 salamanders, with 192 representing New World salamanders that were never tested for Bsal previously. Bsal was not detected, and Bd was mostly present at low prevalence except for one site in the Andes.

Multiple drivers, scales, and interactions influence southern Appalachian stream salamander occupancy

USGS Publications Warehouse

Cecala, Kristen K.; Maerz, John C.; Halstead, Brian J.; Frisch, John R.; Gragson, Ted L.; Hepinstall-Cymerman, Jeffrey; Leigh, David S.; Jackson, C. Rhett; Peterson, James T.; Pringle, Catherine M.

2018-01-01

Understanding how factors that vary in spatial scale relate to population abundance is vital to forecasting species responses to environmental change. Stream and river ecosystems are inherently hierarchical, potentially resulting in organismal responses to fine‐scale changes in patch characteristics that are conditional on the watershed context. Here, we address how populations of two salamander species are affected by interactions among hierarchical processes operating at different scales within a rapidly changing landscape of the southern Appalachian Mountains. We modeled reach‐level occupancy of larval and adult black‐bellied salamanders (Desmognathus quadramaculatus) and larval Blue Ridge two‐lined salamanders (Eurycea wilderae) as a function of 17 different terrestrial and aquatic predictor variables that varied in spatial extent. We found that salamander occurrence varied widely among streams within fully forested catchments, but also exhibited species‐specific responses to changes in local conditions. While D. quadramaculatus declined predictably in relation to losses in forest cover, larval occupancy exhibited the strongest negative response to forest loss as well as decreases in elevation. Conversely, occupancy of E. wilderae was unassociated with watershed conditions, only responding negatively to higher proportions of fast‐flowing stream habitat types. Evaluation of hierarchical relationships demonstrated that most fine‐scale variables were closely correlated with broad watershed‐scale variables, suggesting that local reach‐scale factors have relatively smaller effects within the context of the larger landscape. Our results imply that effective management of southern Appalachian stream salamanders must first focus on the larger scale condition of watersheds before management of local‐scale conditions should proceed. Our findings confirm the results of some studies while refuting the results of others, which may indicate that

Rank Order Coding: a Retinal Information Decoding Strategy Revealed by Large-Scale Multielectrode Array Retinal Recordings.

PubMed

Portelli, Geoffrey; Barrett, John M; Hilgen, Gerrit; Masquelier, Timothée; Maccione, Alessandro; Di Marco, Stefano; Berdondini, Luca; Kornprobst, Pierre; Sernagor, Evelyne

2016-01-01

How a population of retinal ganglion cells (RGCs) encodes the visual scene remains an open question. Going beyond individual RGC coding strategies, results in salamander suggest that the relative latencies of a RGC pair encode spatial information. Thus, a population code based on this concerted spiking could be a powerful mechanism to transmit visual information rapidly and efficiently. Here, we tested this hypothesis in mouse by recording simultaneous light-evoked responses from hundreds of RGCs, at pan-retinal level, using a new generation of large-scale, high-density multielectrode array consisting of 4096 electrodes. Interestingly, we did not find any RGCs exhibiting a clear latency tuning to the stimuli, suggesting that in mouse, individual RGC pairs may not provide sufficient information. We show that a significant amount of information is encoded synergistically in the concerted spiking of large RGC populations. Thus, the RGC population response described with relative activities, or ranks, provides more relevant information than classical independent spike count- or latency- based codes. In particular, we report for the first time that when considering the relative activities across the whole population, the wave of first stimulus-evoked spikes is an accurate indicator of stimulus content. We show that this coding strategy coexists with classical neural codes, and that it is more efficient and faster. Overall, these novel observations suggest that already at the level of the retina, concerted spiking provides a reliable and fast strategy to rapidly transmit new visual scenes.

Rod outer segment retinol formation is independent of Abca4, arrestin, rhodopsin kinase, and rhodopsin palmitylation.

PubMed

Blakeley, Lorie R; Chen, Chunhe; Chen, Ching-Kang; Chen, Jeannie; Crouch, Rosalie K; Travis, Gabriel H; Koutalos, Yiannis

2011-06-01

The reactive aldehyde all-trans retinal is released in rod photoreceptor outer segments by photoactivated rhodopsin and is eliminated through reduction to all-trans retinol. This study was undertaken to determine whether all-trans retinol formation depends on Abca4, arrestin, rhodopsin kinase, and the palmitylation of rhodopsin, all of which are factors that affect the release and sequestration of all-trans retinal. Experiments were performed in isolated retinas and single living rods derived from 129/sv wild-type mice and Abca4-, arrestin-, and rhodopsin kinase-deficient mice and in genetically modified mice containing unpalmitylated rhodopsin. Formation of all-trans retinol was measured by imaging its fluorescence and by HPLC of retina extracts. The release of all-trans retinal from photoactivated rhodopsin was measured in purified rod outer segment membranes according to the increase in tryptophan fluorescence. All experiments were performed at 37°C. The kinetics of all-trans retinol formation in the different types of genetically modified mice are in reasonable agreement with those in wild-type animals. The kinetics of all-trans retinol formation in 129/sv mice are similar to those in C57BL/6, although the latter are known to regenerate rhodopsin much more slowly. The release of all-trans retinal from rhodopsin in purified membranes is significantly faster than the formation of all-trans retinol in intact cells and is independent of the presence of the palmitate groups. The regeneration of rhodopsin and the recycling of its chromophore are not strongly coupled. Neither the activities of Abca4, rhodopsin kinase, and arrestin, nor the palmitylation of rhodopsin affects the formation of all-trans retinol.

Kinetics of Exocytosis Is Faster in Cones Than in Rods

PubMed Central

Rabl, Katalin; Cadetti, Lucia; Thoreson, Wallace B.

2006-01-01

Cone-driven responses of second-order retinal neurons are considerably faster than rod-driven responses. We examined whether differences in the kinetics of synaptic transmitter release from rods and cones may contribute to differences in postsynaptic response kinetics. Exocytosis from rods and cones was triggered by membrane depolarization and monitored in two ways: (1) by measuring EPSCs evoked in second-order neurons by depolarizing steps applied to presynaptic rods or cones during simultaneous paired whole-cell recordings or (2) by direct measurements of exocytotic increases in membrane capacitance. The kinetics of release was assessed by varying the length of the depolarizing test step. Both measures of release revealed two kinetic components to the increase in exocytosis as a function of the duration of a step depolarization. In addition to slow sustained components in both cell types, the initial fast component of exocytosis had a time constant of <5 ms in cones, >10-fold faster than that of rods. Rod/cone differences in the kinetics of release were substantiated by a linear correlation between depolarization-evoked capacitance increases and EPSC charge transfer. Experiments on isolated rods indicate that the slower kinetics of exocytosis from rods was not a result of rod–rod coupling. The initial rapid release of vesicles from cones can shape the postsynaptic response and may contribute to the faster responses of cone-driven cells observed at light offset. PMID:15872111

Exceptional soft tissues preservation in a mummified frog-eating Eocene salamander.

PubMed

Tissier, Jérémy; Rage, Jean-Claude; Laurin, Michel

2017-01-01

Fossils are almost always represented by hard tissues but we present here the exceptional case of a three-dimensionally preserved specimen that was 'mummified' (likely between 40 and 34 million years ago) in a terrestrial karstic environment. This fossil is the incomplete body of a salamander, Phosphotriton sigei , whose skeleton and external morphology are well preserved, as revealed by phase-contrast synchrotron X-ray microtomography. In addition, internal structures composed of soft tissues preserved in three dimensions are now identified: a lung, the spinal cord, a lumbosacral plexus, the digestive tract, muscles and urogenital organs that may be cloacal glands. These are among the oldest known cases of three-dimensional preservation of these organs in vertebrates and shed light on the ecology of this salamander. Indeed, the digestive tract contains remains of a frog, which represents the only known case of an extinct salamander that fed on a frog, an extremely rare type of predation in extant salamanders. These new data improve our scarce knowledge on soft tissue anatomy of early urodeles and should prove useful for future biologists and palaeontologists working on urodele evolutionary biology. We also suggest that the presence of bat guano and carcasses represented a close source of phosphorus, favouring preservation of soft tissues. Bone microanatomy indicates that P. sigei was likely amphibious or terrestrial, and was probably not neotenic.

The Chinese giant salamander exemplifies the hidden extinction of cryptic species.

PubMed

Yan, Fang; Lü, Jingcai; Zhang, Baolin; Yuan, Zhiyong; Zhao, Haipeng; Huang, Song; Wei, Gang; Mi, Xue; Zou, Dahu; Xu, Wei; Chen, Shu; Wang, Jie; Xie, Feng; Wu, Minyao; Xiao, Hanbin; Liang, Zhiqiang; Jin, Jieqiong; Wu, Shifang; Xu, CunShuan; Tapley, Benjamin; Turvey, Samuel T; Papenfuss, Theodore J; Cunningham, Andrew A; Murphy, Robert W; Zhang, Yaping; Che, Jing

2018-05-21

Overexploitation, habitat destruction, human-driven climate change and disease spread are resulting in the extinction of innumerable species, with amphibians being hit harder than most other groups [1]. Few species of amphibians are widespread, and those that are often represent complexes of multiple cryptic species. This is especially true for range-restricted salamanders [2]. Here, we used the widespread and critically endangered Chinese giant salamander (Andrias davidianus) to show how genetically uninformed management efforts can negatively affect species conservation. We find that this salamander consists of at least five species-level lineages. However, the extensive recent translocation of individuals between farms, where the vast majority of extant salamanders now live, has resulted in genetic homogenization. Mitochondrial DNA (mtDNA) haplotypes from northern China now predominate in farms. Unfortunately, hybrid offspring are being released back into the wild under well-intentioned, but misguided, conservation management. Our findings emphasize the necessity of genetic assessments for seemingly well-known, widespread species in conservation initiatives. Species serve as the primary unit for protection and management in conservation actions [3], so determining the taxonomic status of threatened species is a major concern, especially for amphibians. The level of threat to amphibians may be underestimated, and existing conservation strategies may be inadvertently harmful if conducted without genetic assessment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Retinitis pigmentosa: genes and disease mechanisms.

PubMed

Ferrari, Stefano; Di Iorio, Enzo; Barbaro, Vanessa; Ponzin, Diego; Sorrentino, Francesco S; Parmeggiani, Francesco

2011-06-01

Retinitis pigmentosa (RP) is a group of inherited disorders affecting 1 in 3000-7000 people and characterized by abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium of the retina which lead to progressive visual loss. RP can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. While usually limited to the eye, RP may also occur as part of a syndrome as in the Usher syndrome and Bardet-Biedl syndrome. Over 40 genes have been associated with RP so far, with the majority of them expressed in either the photoreceptors or the retinal pigment epithelium. The tremendous heterogeneity of the disease makes the genetics of RP complicated, thus rendering genotype-phenotype correlations not fully applicable yet. In addition to the multiplicity of mutations, in fact, different mutations in the same gene may cause different diseases. We will here review which genes are involved in the genesis of RP and how mutations can lead to retinal degeneration. In the future, a more thorough analysis of genetic and clinical data together with a better understanding of the genotype-phenotype correlation might allow to reveal important information with respect to the likelihood of disease development and choices of therapy.

Retinitis Pigmentosa: Genes and Disease Mechanisms

PubMed Central

Ferrari, Stefano; Di Iorio, Enzo; Barbaro, Vanessa; Ponzin, Diego; Sorrentino, Francesco S; Parmeggiani, Francesco

2011-01-01

Retinitis pigmentosa (RP) is a group of inherited disorders affecting 1 in 3000-7000 people and characterized by abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium of the retina which lead to progressive visual loss. RP can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. While usually limited to the eye, RP may also occur as part of a syndrome as in the Usher syndrome and Bardet-Biedl syndrome. Over 40 genes have been associated with RP so far, with the majority of them expressed in either the photoreceptors or the retinal pigment epithelium. The tremendous heterogeneity of the disease makes the genetics of RP complicated, thus rendering genotype-phenotype correlations not fully applicable yet. In addition to the multiplicity of mutations, in fact, different mutations in the same gene may cause different diseases. We will here review which genes are involved in the genesis of RP and how mutations can lead to retinal degeneration. In the future, a more thorough analysis of genetic and clinical data together with a better understanding of the genotype-phenotype correlation might allow to reveal important information with respect to the likelihood of disease development and choices of therapy. PMID:22131869

A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration

PubMed Central

Chavali, Venkata R.M.; Khan, Naheed W.; Cukras, Catherine A.; Bartsch, Dirk-Uwe; Jablonski, Monica M.; Ayyagari, Radha

2011-01-01

Late-onset retinal macular degeneration (L-ORD) is an autosomal dominant inherited disorder caused by a single missense mutation (S163R) in the CTRP5/C1QTNF5 protein. Early phenotypic features of L-ORD include: dark adaptation abnormalities, nyctalopia, and drusen deposits in the peripheral macular region. Apart from posterior segment abnormalities, these patients also develop abnormally long anterior lens zonules. In the sixth decade of life the rod and cone function declines, accompanied by electroretinogram (ERG) abnormalities. Some patients also develop choroidal neovascularization and glaucoma. In order to understand the disease pathology and mechanisms involved in retinal dystrophy, we generated a knock-in (Ctrp5+/−) mouse model carrying the disease-associated mutation in the mouse Ctrp5/C1QTNF5 gene. These mice develop slower rod-b wave recovery consistent with early dark adaptation abnormalities, accumulation of hyperautofluorescence spots, retinal pigment epithelium abnormalities, drusen, Bruch's membrane abnormalities, loss of photoreceptors, and retinal vascular leakage. The Ctrp5+/−mice, which have most of the pathological features of age-related macular degeneration, are unique and may serve as a valuable model both to understand the molecular pathology of late-onset retinal degeneration and to evaluate therapies. PMID:21349921

High sensitivity rod photoreceptor input to the blue-yellow color opponent pathway in macaque retina

PubMed Central

Field, Greg D.; Greschner, Martin; Gauthier, Jeffrey L.; Rangel, Carolina; Shlens, Jonathon; Sher, Alexander; Marshak, David W.; Litke, Alan M.; Chichilnisky, E.J.

2009-01-01

Small bistratified cells (SBCs) in the primate retina carry a major blue-yellow opponent signal to the brain. Here we show that SBCs also carry signals from rod photoreceptors, with the same sign as S cone input. SBCs exhibited robust responses under low scotopic conditions (<0.01 P*/rod/s). Physiological and anatomical experiments indicated that this rod input arose from the AII amacrine cell mediated rod pathway. Rod and cone signals were both present in SBCs at mesopic light levels. We discuss three implications of these findings. First, more retinal circuits than previously thought may multiplex rod and cone signals, efficiently exploiting the limited number of optic nerve fibers. Second, signals from AII amacrine cells may diverge to most or all of the <20 RGC types in the peripheral primate retina. Third, rod input to SBCs may be the substrate for behavioral biases toward perception of blue at mesopic light levels. PMID:19668201

Effects of hatching time for larval ambystomatid salamanders

USGS Publications Warehouse

Boone, M.D.; Scott, D.E.; Niewiarowski, P.H.

2002-01-01

In aquatic communities, the phenology of breeding may influence species interactions. In the early-breeding marbled salamander, Ambystoma opacum, timing of pond filling may determine whether interactions among larvae are competitive or predatory. The objectives of our studies were to determine how time of egg hatching affected size, larval period, and survival to metamorphosis in A. opacum, and if early-hatching in A. opacum influenced the competitive and predator-prey relationships with smaller larvae of the mole salamander, Ambystoma talpoideum. Salamander larvae were reared from hatching through metamorphosis in large, outdoor enclosures located in a natural temporary pond in Aiken County, South Carolina, in two experiments. In study 1, we reared early- and late-hatching A. opacum larvae separately from hatching through metamorphosis. In study 2, we examined how early- versus late-hatching A. opacum affected a syntopic species, A. talpoideum. In general, early-hatching A. opacum were larger and older at metamorphosis, had greater survival, and left the pond earlier than late-hatching larvae. Ambystoma talpoideum reared in the presence of early-hatching A. opacum had lower survival than in controls, suggesting that A. opacum may predate upon A. talpoideum when they gain a growth advantage over later-hatching larvae. Our studies demonstrate that time of pond filling and phenology of breeding may influence population dynamics and alter the nature of relationships that develop among species.

Photopigment quenching is Ca2+ dependent and controls response duration in salamander L-cone photoreceptors

PubMed Central

2010-01-01

The time scale of the photoresponse in photoreceptor cells is set by the slowest of the steps that quench the light-induced activity of the phototransduction cascade. In vertebrate photoreceptor cells, this rate-limiting reaction is thought to be either shutoff of catalytic activity in the photopigment or shutoff of the pigment's effector, the transducin-GTP–phosphodiesterase complex. In suction pipette recordings from isolated salamander L-cones, we found that preventing changes in internal [Ca2+] delayed the recovery of the light response and prolonged the dominant time constant for recovery. Evidence that the Ca2+-sensitive step involved the pigment itself was provided by the observation that removal of Cl− from the pigment's anion-binding site accelerated the dominant time constant for response recovery. Collectively, these observations indicate that in L-cones, unlike amphibian rods where the dominant time constant is insensitive to [Ca2+], pigment quenching rate limits recovery and provides an additional mechanism for modulating the cone response during light adaptation. PMID:20231373

Effect of acute low body temperature on predatory behavior and prey-capture efficiency in a plethodontid salamander.

PubMed

Marvin, Glenn A; Davis, Kayla; Dawson, Jacob

2016-05-01

The low-temperature limit for feeding in some salamander species (Desmognathus, Plethodontidae) has been inferred from field studies of seasonal variation in salamander activity and gut contents, which could not determine whether feeding is more dependent on environmental conditions influencing salamander foraging behavior or prey availability and movement. We performed two controlled laboratory experiments to examine the effect of short-term (acute) low body temperature on predatory behavior and prey-capture efficiency in a semiaquatic plethodontid salamander (Desmognathus conanti). In the first experiment, we quantified variation in the feeding responses of cold salamanders (at 1, 3, 5 and 7°C) to a video recording of a walking, warm (15°C) cricket to determine the lower thermal limit for predatory behavior, independent of any temperature effect on movement of prey. Experimental-group salamanders exhibited vigorous feeding responses at 5 and 7°C, large variation in feeding responses both among and within individuals (over time) at 3°C, and little to no feeding response at 1°C. Feeding responses at both 1 and 3°C were significantly less than at each higher temperature, whereas responses of control-group individuals at 15°C did not vary over time. In the second experiment, we quantified feeding by cold salamanders (at 3, 5, 7 and 11°C) on live, warm crickets to examine thermal effects on prey-capture ability. The mean feeding response to live crickets was significantly less at 3°C than at higher temperatures; however, 50% of salamanders captured and ingested prey with high efficiency at this temperature. We conclude that many individuals stalk and capture prey at very low temperatures (down to 3°C). Our results support a growing body of data that indicate many plethodontid salamanders feed at temperatures only a few degrees above freezing. Copyright © 2016 Elsevier Inc. All rights reserved.

Negative electroretinograms in pericentral pigmentary retinal degeneration.

PubMed

Hotta, Kazuki; Kondo, Mineo; Nakamura, Makoto; Hotta, Junko; Terasaki, Hiroko; Miyake, Yozo; Hida, Tetsuo

2006-01-01

The clinical presentation and electrophysiological findings are described of three consecutive cases with pericentral pigmentary retinal degeneration. The responses to bright flashes after dark adaptation showed negative waveform shape in all cases. Rod responses were strongly reduced compared with cone responses. Cone electroretinograms elicited by long-duration stimuli showed greater loss of the on-response than the off-response. The ratio of the on-response amplitude to off-response amplitude of these patients (0.52 +/- 0.12; mean +/- SD, n = 6) was significantly smaller than that of normal subject (0.83 +/- 0.21; mean +/- SD, n = 8) (Mann-Whitney U-test, P < 0.01). The electrophysiological findings of these cases suggest a greater defect of inner retinal function, especially in transmission between photoreceptors and depolarizing bipolar cells.

Diet of the Del Norte Salamander (Plethodon elongatus): Differences by age, gender, and season.

Treesearch

Clara A. Wheeler; Nancy E. Karraker; Hartwell H. Welsh; Lisa M. Ollivier

2007-01-01

Terrestrial salamanders are integral components of forest ecosystems and the examination of their feeding habits may provide useful information regarding various ecosystem processes. We studied the diet of the Del Norte Salamander (Plethodon elongatus) and assessed diet differences between age classes, genders, and seasons. The stomachs of 309...

Learned arbitrary responses to light in mice without rods or cones

NASA Astrophysics Data System (ADS)

Mrosovsky, N.; Salmon, Peggy

2002-10-01

The aim of this investigation was to discover whether mice lacking classical photoreceptors (rods and cones) can nevertheless be trained to respond to light. Mice with the coneless (cl) transgene have an attenuated diphtheria toxin fused to a cone opsin promotor. Mutant mice homozygous for the retinal degeneration (rd) gene undergo loss of their rods. By mating these two strains, mice lacking both cones and rods can be generated (Lucas et al. 1999). Such coneless-rodless mice were able to use light as a signal to make a behavioural response to avoid impending shock. Nevertheless, especially initially, they used the light as a cue less often than wildtype controls, indicating that normally the rods and cones are used for such responses. However, other photoreceptors are able to take over this role to some extent. When the lights were covered with opaque material, the performance of rodless-coneless mice dropped to chance level, indicating that they had been using the light as a cue for avoidance.

Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa.

PubMed

Beltran, William A; Cideciyan, Artur V; Lewin, Alfred S; Iwabe, Simone; Khanna, Hemant; Sumaroka, Alexander; Chiodo, Vince A; Fajardo, Diego S; Román, Alejandro J; Deng, Wen-Tao; Swider, Malgorzata; Alemán, Tomas S; Boye, Sanford L; Genini, Sem; Swaroop, Anand; Hauswirth, William W; Jacobson, Samuel G; Aguirre, Gustavo D

2012-02-07

Hereditary retinal blindness is caused by mutations in genes expressed in photoreceptors or retinal pigment epithelium. Gene therapy in mouse and dog models of a primary retinal pigment epithelium disease has already been translated to human clinical trials with encouraging results. Treatment for common primary photoreceptor blindness, however, has not yet moved from proof of concept to the clinic. We evaluated gene augmentation therapy in two blinding canine photoreceptor diseases that model the common X-linked form of retinitis pigmentosa caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, which encodes a photoreceptor ciliary protein, and provide evidence that the therapy is effective. After subretinal injections of adeno-associated virus-2/5-vectored human RPGR with human IRBP or GRK1 promoters, in vivo imaging showed preserved photoreceptor nuclei and inner/outer segments that were limited to treated areas. Both rod and cone photoreceptor function were greater in treated (three of four) than in control eyes. Histopathology indicated normal photoreceptor structure and reversal of opsin mislocalization in treated areas expressing human RPGR protein in rods and cones. Postreceptoral remodeling was also corrected: there was reversal of bipolar cell dendrite retraction evident with bipolar cell markers and preservation of outer plexiform layer thickness. Efficacy of gene therapy in these large animal models of X-linked retinitis pigmentosa provides a path for translation to human treatment.

Response of two terrestrial salamander species to spring burning in the Sierra Nevada, California

Treesearch

Karen E. Bagne; Kathryn L. Purcell

2009-01-01

Terrestrial salamanders may be vulnerable to prescribed fire applications due to their moist, permeable skin and limited mobility. We present data collected on terrestrial salamander populations in a ponderosa pine-dominated forest in the Sierra Nevada where fire was applied in the spring. Two species, Sierra ensatina (Ensatina eschscholtzi platensis...

Novel Animal Model of Crumbs-Dependent Progressive Retinal Degeneration That Targets Specific Cone Subtypes.

PubMed

Fu, Jinling; Nagashima, Mikiko; Guo, Chuanyu; Raymond, Pamela A; Wei, Xiangyun

2018-01-01

Human Crb1 is implicated in some forms of retinal degeneration, suggesting a role in photoreceptor maintenance. Multiple Crumbs (Crb) polarity genes are expressed in vertebrate retina, although their functional roles are not well understood. To gain further insight into Crb and photoreceptor maintenance, we compared retinal cell densities between wild-type and Tg(RH2-2:Crb2b-sfEX/RH2-2:GFP)pt108b transgenic zebrafish, in which the extracellular domain of Crb2b-short form (Crb2b-sfEX) is expressed in the retina as a secreted protein, which disrupts the planar organization of RGB cones (red, green, and blue) by interfering with Crb2a/2b-based cone-cone adhesion. We used standard morphometric techniques to assess age-related changes in retinal cell densities in adult zebrafish (3 to 27 months old), and to assess effects of the Crb2b-sfEX transgene on retinal structure and photoreceptor densities. Linear cell densities were measured in all retinal layers in radial sections with JB4-Feulgen histology. Planar (surface) densities of cones were determined in retinal flat-mounts. Cell counts from wild-type and pt108b transgenic fish were compared with both a "photoreceptor maintenance index" and statistical analysis of cell counts. Age-related changes in retinal cell linear densities and cone photoreceptor planar densities in wild-type adult zebrafish provided a baseline for analysis. Expression of Crb2b-sfEX caused progressive and selective degeneration of RGB cones, but had no effect on ultraviolet-sensitive (UV) cones, and increased numbers of rod photoreceptors. These differential responses of RGB cones, UV cones, and rods to sustained exposure to Crb2b-sfEX suggest that Crb-based photoreceptor maintenance mechanisms are highly selective.

Climate-mediated competition in a high-elevation salamander community

USGS Publications Warehouse

Dallalio, Eric A.; Brand, Adrianne B,; Grant, Evan H. Campbell

2017-01-01

The distribution of the federally endangered Shenandoah Salamander (Plethodon shenandoah) is presumed to be limited by competition with the Red-backed Salamander (Plethodon cinereus). In particular, the current distribution of P. shenandoah is understood to be restricted to warmer and drier habitats because of interspecific interactions. These habitats may be particularly sensitive to climate change, though the influence of competition may also be affected by temperature and relative humidity. We investigated the response of P. shenandoah to competition with P. cinereus under four climate scenarios in 3-dimensional mesocosms. The results suggest that, although climate change may alleviate competitive pressure from P. cinereus, warmer temperatures may also significantly influence the persistence of the species across its known range.

Role of habitat complexity in predator-prey dynamics between an introduced fish and larval Long-toed Salamanders (Ambystoma macrodactylum)

USGS Publications Warehouse

Kenison, Erin K; Litt, Andrea R.; Pilliod, David S.; McMahon, Tom E

2016-01-01

Predation by nonnative fishes has reduced abundance and increased extinction risk for amphibian populations worldwide. Although rare, fish and palatable amphibians have been observed to coexist where aquatic vegetation and structural complexity provide suitable refugia. We examined whether larval long-toed salamanders (Ambystoma macrodactylum Baird, 1849) increased use of vegetation cover in lakes with trout and whether adding vegetation structure could reduce predation risk and nonconsumptive effects (NCEs), such as reductions in body size and delayed metamorphosis. We compared use of vegetation cover by larval salamanders in lakes with and without trout and conducted a field experiment to investigate the influence of added vegetation structure on salamander body morphology and life history. The probability of catching salamanders in traps in lakes with trout was positively correlated with the proportion of submerged vegetation and surface cover. Growth rates of salamanders in enclosures with trout cues decreased as much as 85% and the probability of metamorphosis decreased by 56%. We did not find evidence that adding vegetation reduced NCEs in experimental enclosures, but salamanders in lakes with trout utilized more highly-vegetated areas which suggests that adding vegetation structure at the scale of the whole lake may facilitate coexistence between salamanders and introduced trout.

Habitat relationships of eastern red-backed salamanders (Plethodon cinereus) in Appalachian agroforestry and grazing systems

Treesearch

Breanna L. Riedel; Kevin R. Russell; W. Mark Ford; Katherine P. O' Neill; Harry W. Godwin

2008-01-01

Woodland salamander responses to either traditional grazing or silvopasture systems are virtually unknown. An information-theoretic modelling approach was used to evaluate responses of red-backed salamanders (Plethodon cinereus) to silvopasture and meadow conversions in southern West Virginia. Searches of area-constrained plots and artificial...

Long bone histology of the stem salamander Kokartus honorarius (Amphibia: Caudata) from the Middle Jurassic of Kyrgyzstan

PubMed Central

Skutschas, Pavel; Stein, Koen

2015-01-01

Kokartus honorarius from the Middle Jurassic (Bathonian) of Kyrgyzstan is one of the oldest salamanders in the fossil record, characterized by a mixture of plesiomorphic morphological features and characters shared with crown-group salamanders. Here we present a detailed histological analysis of its long bones. The analysis of a growth series demonstrates a significant histological maturation during ontogeny, expressed by the progressive appearance of longitudinally oriented primary vascular canals, primary osteons, growth marks, remodelling features in primary bone tissues, as well as progressive resorption of the calcified cartilage, formation of endochondral bone and development of cartilaginous to bony trabeculae in the epiphyses. Apart from the presence of secondary osteons, the long bone histology of Kokartus is very similar to that of miniaturized temnospondyls, other Jurassic stem salamanders, miniaturized seymouriamorphs and modern crown-group salamanders. We propose that the presence of secondary osteons in Kokartus honorarius is a plesiomorphic feature, and the loss of secondary osteons in the long bones of crown-group salamanders as well as in those of miniaturized temnospondyls is the result of miniaturization processes. Hitherto, all stem salamander long bong histology (Kokartus, Marmorerpeton and ‘salamander A’) has been generally described as having paedomorphic features (i.e. the presence of Katschenko's Line and a layer of calcified cartilage), these taxa were thus most likely neotenic forms. The absence of clear lines of arrested growth and annuli in long bones of Kokartus honorarius suggests that the animals lived in an environment with stable local conditions. PMID:25682890

Long bone histology of the stem salamander Kokartus honorarius (Amphibia: Caudata) from the Middle Jurassic of Kyrgyzstan.

PubMed

Skutschas, Pavel; Stein, Koen

2015-04-01

Kokartus honorarius from the Middle Jurassic (Bathonian) of Kyrgyzstan is one of the oldest salamanders in the fossil record, characterized by a mixture of plesiomorphic morphological features and characters shared with crown-group salamanders. Here we present a detailed histological analysis of its long bones. The analysis of a growth series demonstrates a significant histological maturation during ontogeny, expressed by the progressive appearance of longitudinally oriented primary vascular canals, primary osteons, growth marks, remodelling features in primary bone tissues, as well as progressive resorption of the calcified cartilage, formation of endochondral bone and development of cartilaginous to bony trabeculae in the epiphyses. Apart from the presence of secondary osteons, the long bone histology of Kokartus is very similar to that of miniaturized temnospondyls, other Jurassic stem salamanders, miniaturized seymouriamorphs and modern crown-group salamanders. We propose that the presence of secondary osteons in Kokartus honorarius is a plesiomorphic feature, and the loss of secondary osteons in the long bones of crown-group salamanders as well as in those of miniaturized temnospondyls is the result of miniaturization processes. Hitherto, all stem salamander long bong histology (Kokartus, Marmorerpeton and 'salamander A') has been generally described as having paedomorphic features (i.e. the presence of Katschenko's Line and a layer of calcified cartilage), these taxa were thus most likely neotenic forms. The absence of clear lines of arrested growth and annuli in long bones of Kokartus honorarius suggests that the animals lived in an environment with stable local conditions. © 2015 Anatomical Society.

Wide-field fundus autofluorescence abnormalities and visual function in patients with cone and cone-rod dystrophies.

PubMed

Oishi, Maho; Oishi, Akio; Ogino, Ken; Makiyama, Yukiko; Gotoh, Norimoto; Kurimoto, Masafumi; Yoshimura, Nagahisa

2014-05-20

To evaluate the clinical utility of wide-field fundus autofluorescence (FAF) in patients with cone dystrophy and cone-rod dystrophy. Sixteen patients with cone dystrophy (CD) and 41 patients with cone-rod dystrophy (CRD) were recruited at one institution. The right eye of each patient was included for analysis. We obtained wide-field FAF images using a ultra-widefield retinal imaging device and measured the area of abnormal FAF. The association between the area of abnormal FAF and the results of visual acuity measurements, kinetic perimetry, and electroretinography (ERG) were investigated. The mean age of the participants was 51.4 ± 17.4 years, and the mean logarithm of the minimum angle of resolution was 1.00 ± 0.57. The area of abnormal FAF correlated with the scotoma measured by the Goldman perimetry I/4e isopter (ρ = 0.79, P < 0.001). The area also correlated with amplitudes of the rod ERG (ρ = -0.63, P < 0.001), combined ERG a-wave (ρ = -0.72, P < 0.001), combined ERG b-wave (ρ = -0.66, P < 0.001), cone ERG (ρ = -0.44, P = 0.001), and flicker ERG (ρ = -0.47, P < 0.001). The extent of abnormal FAF reflects the severity of functional impairment in patients with cone-dominant retinal dystrophies. Fundus autofluorescence measurements are useful for predicting retinal function in these patients. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Mathematical models of retinitis pigmentosa: The oxygen toxicity hypothesis.

PubMed

Roberts, Paul A; Gaffney, Eamonn A; Luthert, Philip J; Foss, Alexander J E; Byrne, Helen M

2017-07-21

The group of genetically mediated diseases, known collectively as retinitis pigmentosa (RP), cause retinal degeneration and, hence, loss of vision. The most common inherited retinal degeneration, RP is currently untreatable. The retina detects light using cells known as photoreceptors, of which there are two types: rods and cones. In RP, genetic mutations cause patches of photoreceptors to degenerate and typically directly affect either rods or cones, but not both. During disease progression, degenerate patches spread and the unaffected photoreceptor type also begins to degenerate. The cause underlying these phenomena is currently unknown. The oxygen toxicity hypothesis proposes that secondary photoreceptor loss is due to hyperoxia (toxically high oxygen levels), which results from the decrease in oxygen uptake following the initial loss of photoreceptors. In this paper, we construct mathematical models, formulated as 1D systems of partial differential equations, to investigate this hypothesis. Using a combination of numerical simulations, asymptotic analysis and travelling wave analysis, we find that degeneration may spread due to hyperoxia, and generate spatio-temporal patterns of degeneration similar to those seen in vivo. We determine the conditions under which a degenerate patch will spread and show that the wave speed of degeneration is a monotone decreasing function of the local photoreceptor density. Lastly, the effects of treatment with antioxidants and trophic factors, and of capillary loss, upon the dynamics of photoreceptor loss and recovery are considered. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

[Early therapeutic trials for retinitis pigmentosa].

PubMed

Dufier, Jean-Louis

2003-01-01

Non syndromic forms of Retinitis Pigmentosa (RP) constitute a collection of clinically and genetically heterogeneous inherited retinal degenerative diseases. They are characterized by a bilateral progressive visual loss susceptible to cause blindness. These diseases are transmitted through pedigrees according to all known modes of inheritance. They are bilateral and usually start during infancy. However, very early clinical presentations exist, such as those observed in children affected by Leber Congenital Amaurosis, as well as late onset autosomal dominant forms of retinitis pigmentosa. The characteristic clinical aspect of the rod-cone RP dystrophies is marked by alterations of the peripheral retina associated with a night blindness and a progressive narrowing of the visual field. The ophthalmoscopic examination of RP patients commonly reveals thin retinal arteries and scattered pigmentary accumulations. In contrast, there are cone rod retinal dystrophies whose onset is marked by a decreased visual acuity before the appearance of any visual field alteration. Some forms of RPs display an ocular fundus devoid of any pigmentary alteration. Syndromic forms of RPs are not uncommon. The association of deafness with RP is detected in nearly 30% of the patients. Other associations with RP can include mental deficiency, facial dysmorphy, microcephaly, obesity, kidney deficiency, immune deficiencies, metabolic disorders. The existence of such syndromic forms of RP localizes RPs at the crossroad of several medical specialties. A long lasting collaboration between our department of ophthalmology and the department of medical genetics of the Necker-Sick Children Hospital has allowed us to establish numerous genotype-phenotype correlations, especially in LCA and Stargardt's disease. ABCR gene mutations cause Stargardt disease. ABCR mutations may also cause some types of Ages Related Macular Degenerations (AMD). Nowadays, there is no known efficient therapy available for

Evaluating multi-level models to test occupancy state responses of Plethodontid salamanders

USGS Publications Warehouse

Kroll, Andrew J.; Garcia, Tiffany S.; Jones, Jay E.; Dugger, Catherine; Murden, Blake; Johnson, Josh; Peerman, Summer; Brintz, Ben; Rochelle, Michael

2015-01-01

Plethodontid salamanders are diverse and widely distributed taxa and play critical roles in ecosystem processes. Due to salamander use of structurally complex habitats, and because only a portion of a population is available for sampling, evaluation of sampling designs and estimators is critical to provide strong inference about Plethodontid ecology and responses to conservation and management activities. We conducted a simulation study to evaluate the effectiveness of multi-scale and hierarchical single-scale occupancy models in the context of a Before-After Control-Impact (BACI) experimental design with multiple levels of sampling. Also, we fit the hierarchical single-scale model to empirical data collected for Oregon slender and Ensatina salamanders across two years on 66 forest stands in the Cascade Range, Oregon, USA. All models were fit within a Bayesian framework. Estimator precision in both models improved with increasing numbers of primary and secondary sampling units, underscoring the potential gains accrued when adding secondary sampling units. Both models showed evidence of estimator bias at low detection probabilities and low sample sizes; this problem was particularly acute for the multi-scale model. Our results suggested that sufficient sample sizes at both the primary and secondary sampling levels could ameliorate this issue. Empirical data indicated Oregon slender salamander occupancy was associated strongly with the amount of coarse woody debris (posterior mean = 0.74; SD = 0.24); Ensatina occupancy was not associated with amount of coarse woody debris (posterior mean = -0.01; SD = 0.29). Our simulation results indicate that either model is suitable for use in an experimental study of Plethodontid salamanders provided that sample sizes are sufficiently large. However, hierarchical single-scale and multi-scale models describe different processes and estimate different parameters. As a result, we recommend careful consideration of study questions

Progression of Pro23His Retinopathy in a Miniature Swine Model of Retinitis Pigmentosa

PubMed Central

Scott, Patrick A.; de Castro, Juan P. Fernandez; DeMarco, Paul J.; Ross, Jason W.; Njoka, Josephat; Walters, Eric; Prather, Randall S.; McCall, Maureen A.; Kaplan, Henry J.

2017-01-01

Purpose We characterize the progression of retinopathy in Filial 1 (F1) progeny of a transgenic (Tg) founder miniswine exhibiting severe Pro23His (P23H) retinopathy. Methods The F1 TgP23H miniswine progeny were created by crossing TgP23H founder miniswine 53-1 with wild type (WT) inbred miniature swine. Scotopic (rod-driven) and photopic (cone-driven) retinal functions were evaluated in F1 TgP23H and WT littermates using full field electroretinograms (ffERGs) at 1, 2, 3, 6, 9, 12, and 18 months of age, as well as the Tg founder miniswine at 6 years of age. Miniswine were euthanized and their retinas processed for morphologic evaluation at the light and electron microscopic level. Retinal morphology of a 36-month-old Tg miniswine also was examined. Results Wild type littermates reached mature scotopic and photopic retinal function by 3 months, while TgP23H miniswine showed abnormal scotopic ffERGs at the earliest time point, 1 month, and depressed photopic ffERGs after 2 months. Rod and cone photoreceptors (PR) exhibited morphologic abnormalities and dropout from the outer nuclear layer at 1 month, with only a monolayer of cone PR somata remaining after 2 months. The retinas showed progressive neural remodeling of the outer retina that included dendritic retraction of rod bipolar cells and glial seal formation by Müller cells. The TgP23H founder miniswine showed cone PR with relatively intact morphology exclusive to the area centralis. Conclusions The F1 Tg miniswine and the TgP23H founder miniswine exhibit similar retinopathy. Translational Relevance TgP23H miniswine are a useful large-eye model to study pathogenesis and preservation cone PRs in humans with retinitis pigmentosa. PMID:28316877

Using a GIS model to assess terrestrial salamander response to alternative forest management plans

Treesearch

Eric J. Gustafson; Nathan L. Murphy; Thomas R. Crow

2001-01-01

A GIS model predicting the spatial distribution of terrestrial salamander abundance based on topography and forest age was developed using parameters derived from the literature. The model was tested by sampling salamander abundance across the full range of site conditions used in the model. A regression of the predictions of our GIS model against these sample data...

Microarray analysis of a salamander hopeful monster reveals transcriptional signatures of paedomorphic brain development

PubMed Central

2010-01-01

Background The Mexican axolotl (Ambystoma mexicanum) is considered a hopeful monster because it exhibits an adaptive and derived mode of development - paedomorphosis - that has evolved rapidly and independently among tiger salamanders. Unlike related tiger salamanders that undergo metamorphosis, axolotls retain larval morphological traits into adulthood and thus present an adult body plan that differs dramatically from the ancestral (metamorphic) form. The basis of paedomorphic development was investigated by comparing temporal patterns of gene transcription between axolotl and tiger salamander larvae (Ambystoma tigrinum tigrinum) that typically undergo a metamorphosis. Results Transcript abundances from whole brain and pituitary were estimated via microarray analysis on four different days post hatching (42, 56, 70, 84 dph) and regression modeling was used to independently identify genes that were differentially expressed as a function of time in both species. Collectively, more differentially expressed genes (DEGs) were identified as unique to the axolotl (n = 76) and tiger salamander (n = 292) than were identified as shared (n = 108). All but two of the shared DEGs exhibited the same temporal pattern of expression and the unique genes tended to show greater changes later in the larval period when tiger salamander larvae were undergoing anatomical metamorphosis. A second, complementary analysis that directly compared the expression of 1320 genes between the species identified 409 genes that differed as a function of species or the interaction between time and species. Of these 409 DEGs, 84% exhibited higher abundances in tiger salamander larvae at all sampling times. Conclusions Many of the unique tiger salamander transcriptional responses are probably associated with metamorphic biological processes. However, the axolotl also showed unique patterns of transcription early in development. In particular, the axolotl showed a genome-wide reduction in mRNA abundance

Ecological separation in a polymorphic terrestrial salamander.

PubMed

Anthony, Carl D; Venesky, Matthew D; Hickerson, Cari-Ann M

2008-07-01

1. When studying speciation, researchers commonly examine reproductive isolation in recently diverged populations. Polymorphic species provide an opportunity to examine the role of reproductive isolation in populations that may be in the process of divergence. 2. We examined a polymorphic population of Plethodon cinereus (red-backed salamanders) for evidence of sympatric ecological separation by colour morphology. Recent studies have correlated temperature and climate with colour morphology in this species, but no studies have looked at differences in diet or mate choice between colour morphs. We used artificial cover objects to assess salamander diet, mating preference and surface activity over a 2-year period at a field site in north-eastern Ohio. 3. We detected differences in diet between two colour morphs, striped and unstriped. The diets of striped individuals were significantly more diverse and were made up of more profitable prey than the diets of unstriped salamanders. 4. Opposite sex pairs were made up of individuals of the same colour morph and striped males were found more often with larger females than were unstriped males. 5. We corroborate findings of earlier studies suggesting that the unstriped form is adapted to warmer conditions. Unstriped individuals were the first to withdraw from the forest floor as temperatures fell in the late fall. We found no evidence that the colour morphs responded differently to abiotic factors such as soil moisture and relative humidity, and responses to surface temperatures were also equivocal. 6. We conclude that the two colour morphs exhibit some degree of ecological separation and tend to mate assortatively, but are unlikely to be undergoing divergence given the observed frequency of intermorph pairings.

LOW CONDUCTANCE HCN1 ION CHANNELS AUGMENT THE FREQUENCY RESPONSE OF ROD AND CONE PHOTORECEPTORS

PubMed Central

Barrow, Andrew J.; Wu, Samuel M.

2009-01-01

Hyperpolarization-activated cyclic nucleotide gated (HCN) ion channels are expressed in several tissues throughout the body, including the heart, the CNS, and the retina. HCN channels are found in many neurons in the retina, but their most established role is in generating the hyperpolarization-activated current, Ih, in photoreceptors. This current makes the light response of rod and cone photoreceptors more transient, an effect similar to that of a high-pass filter. A unique property of HCN channels is their small single channel current, which is below the thermal noise threshold of measuring electronics. We use nonstationary fluctuation analysis (NSFA) in the intact retina to estimate the conductance of single HCN channels, revealing a conductance of approximately 650 fS in both rod and cone photoreceptors. We also analyze the properties of HCN channels in salamander rods and cones, from the biophysical to the functional level, showing that HCN1 is the predominant isoform in both cells, and demonstrate how HCN1 channels speed up the light response of both rods and cones under distinct adaptational conditions. We show that in rods and cones, HCN channels increase the natural frequency response of single cells by modifying the photocurrent input, which is limited in its frequency response by the speed of a molecular signaling cascade. In doing so, HCN channels form the first of several systems in the retina that augment the speed of the visual response, allowing an animal to perceive visual stimuli that change more quickly than the underlying photocurrent. PMID:19420251

Light-Emitting Diodes and Cool White Fluorescent Light Similarly Suppress Pineal Gland Melatonin and Maintain Retinal Function and Morphology in the Rat. Part 1

NASA Technical Reports Server (NTRS)

Holley, Daniel C.; Heeke, D.; Mele, G.

1999-01-01

Currently, the light sources most commonly used in animal habitat lighting are cool white fluorescent or incandescent lamps. We evaluated a novel light-emitting diode (LED) light source for use in animal habitat lighting by comparing its effectiveness to cool white fluorescent light (CWF) in suppressing pineal gland melatonin and maintaining normal retinal physiology and morphology in the rat. Results of pineal melatonin suppression experiments showed equal suppression of pineal melatonin concentrations for LED light and CWF light at five different light illuminances (100, 40, 10, 1 and 0.1 lux). There were no significant differences in melatonin suppression between LED and CWF light when compared to unexposed controls. Retinal physiology was evaluated using electroretinography. Results show no differences in a-wave implicit times and amplitudes or b-wave implicit times and amplitudes between 100-lux LED-exposed rats and 100-lux CWF-exposed rats. Results of retinal histology assessment show no differences in retinal thickness rod outer segment length and number of rod nuclei between rats exposed to 100-lux LED and 100-lux CWF for days. Furthermore, the retinal pigmented epithelium and rod outer segments of all eyes observed were in good condition and of normal thickness. This study indicates that LED light does not cause retinal damage and can suppress pineal melatonin at similar intensities as a conventional CWF light source. These data suggest that LED light sources may be suitable replacements for conventional light sources used in the lighting of rodent vivariums while providing many mechanical and economical advantages.

Relative abundance and species richness of terrestrial salamanders on hardwood ecosystem experiment sites before harvesting

Treesearch

Jami E. MacNeil; Rod N. Williams

2013-01-01

Terrestrial salamanders are ideal indicators of forest ecosystem integrity due to their abundance, their role in nutrient cycling, and their sensitivity to environmental change. To understand better how terrestrial salamanders are affected by forest management practices, we monitored species diversity and abundance before implementation of timber harvests within the...

Short-Term Response of Jordan's Salamander to a Shelterwood Timber Harvest in Western North Carolina

Treesearch

Chad E. Bartman; Kathleen C. Parker; Joshua Laerm; Timothy S. McCay

2001-01-01

The effects of shelterwood cutting on the abundance of Jordan's salamander (Plethodon jordani) in western North Carolina were examined during 1997 and 1998. Terrestrial salamander assemblages were sampled before, immediately after, and one year after timber harvest on control and treatment plots to estimate abundance. We also surveyed...

The influence of red-backed salamanders (Plethodon cinereus) on nutrient cycling in Appalachian hardwood forests

Treesearch

Eric B. Sucre; Jessica A. Homyack; Thomas R. Fox; Carola A. Haas

2010-01-01

The use of amphibians as biological indicators of ecosystem health has received considerable attention because of the increasing importance placed upon maintaining biodiversity in forested ecosystems. In this study, we imposed three different eastern red-backed salamander (Plethodon cinereus) treatments: 1) low (n = 4; added 0 salamanders to each...

Survival of spotted salamander eggs in temporary woodland ponds of coastal Maryland

USGS Publications Warehouse

Albers, P.H.; Prouty, R.M.

1987-01-01

Temporary ponds on the Atlantic Coastal Plain in maryland were characterized according to water chemistry, rain input, phytoplankton, zooplankton and use by the spotted salamander Ambystoma maculatum during March-October 1983-1984. Neither the number of egg masses per unit of pond surface (abundance) nor the survival of spotted salamander embryos was significantly correlated (P>0.05) with pond pH. Rainfall during May-July significantly increased the hydrogen ion concentration of 5 of 11 ponds evaluated for the impact of rainfall during the previous 48h and the previous week. Survival of egg masses transferred among eight ponds with pH3.66-4.45 and one pond with pH5.18 was significantly reduced (Psalamander. At the present time, pond longevity, water temperature and possibly, oxygen content, seem more important to spotted salamander reproduction than chemical changes caused by annual acidic deposition.

Persistence and extirpation in invaded landscapes: patch characteristics and connectivity determine effects of non-native predatory fish on native salamanders

USGS Publications Warehouse

Pilliod, David S.; Arkle, Robert S.; Maxell, Bryce A.

2012-01-01

Studies have demonstrated negative effects of non-native, predatory fishes on native amphibians, yet it is still unclear why some amphibian populations persist, while others are extirpated, following fish invasion. We examined this question by developing habitat-based occupancy models for the long-toed salamander (Ambystoma macrodactylum) and nonnative fish using survey data from 1,749 water bodies across 470 catchments in the Northern Rocky Mountains, USA. We first modeled the habitat associations of salamanders at 468 fishless water bodies in 154 catchments where non-native fish were historically, and are currently, absent from the entire catchment. Wethen applied this habitat model to the complete data set to predict the probability of salamander occupancy in each water body, removing any effect of fish presence. Finally, we compared field-observed occurrences of salamanders and fish to modeled probability of salamander occupancy. Suitability models indicated that fish and salamanders had similar habitat preferences, possibly resulting in extirpations of salamander populations from entire catchments where suitable habitats were limiting. Salamanders coexisted with non-native fish in some catchments by using marginal quality, isolated (no inlet or outlet) habitats that remained fishless. They rarely coexisted with fish within individual water bodies and only where habitat quality was highest. Connectivity of water bodies via streams resulted in increased probability of fish invasion and consequently reduced probability of salamander occupancy.These results could be used to identify and prioritize catchments and water bodies where control measures would be most effective at restoring amphibian populations. Our approach could be useful as a framework for improved investigations into questions of persistence and extirpation of native species when non-native species have already become established.

Retinal ganglion cells in the eastern newt Notophthalmus viridescens: topography, morphology, and diversity.

PubMed

Pushchin, Igor I; Karetin, Yuriy A

2009-10-20

The topography and morphology of retinal ganglion cells (RGCs) in the eastern newt were studied. Cells were retrogradely labeled with tetramethylrhodamine-conjugated dextran amines or horseradish peroxidase and examined in retinal wholemounts. Their total number was 18,025 +/- 3,602 (mean +/- SEM). The spatial density of RGCs varied from 2,100 cells/mm(2) in the retinal periphery to 4,500 cells/mm(2) in the dorsotemporal retina. No prominent retinal specializations were found. The spatial resolution estimated from the spatial density of RGCs varied from 1.4 cycles per degree in the periphery to 1.95 cycles per degree in the region of the peak RGC density. A sample of 68 cells was camera lucida drawn and subjected to quantitative analysis. A total of 21 parameters related to RGC morphology and stratification in the retina were estimated. Partitionings obtained by using different clustering algorithms combined with automatic variable weighting and dimensionality reduction techniques were compared, and an effective solution was found by using silhouette analysis. A total of seven clusters were identified and associated with potential cell types. Kruskal-Wallis ANOVA-on-Ranks with post hoc Mann-Whitney U tests showed significant pairwise between-cluster differences in one or more of the clustering variables. The average silhouette values of the clusters were reasonably high, ranging from 0.52 to 0.79. Cells assigned to the same cluster displayed similar morphology and stratification in the retina. The advantages and limitations of the methodology adopted are discussed. The present classification is compared with known morphological and physiological RGC classifications in other salamanders.

Determining the imaging plane of a retinal capillary layer in adaptive optical imaging

NASA Astrophysics Data System (ADS)

Yang, Le-Bao; Hu, Li-Fa; Li, Da-Yu; Cao, Zhao-Liang; Mu, Quan-Quan; Ma, Ji; Xuan, Li

2016-09-01

Even in the early stage, endocrine metabolism disease may lead to micro aneurysms in retinal capillaries whose diameters are less than 10 μm. However, the fundus cameras used in clinic diagnosis can only obtain images of vessels larger than 20 μm in diameter. The human retina is a thin and multiple layer tissue, and the layer of capillaries less than 10 μm in diameter only exists in the inner nuclear layer. The layer thickness of capillaries less than 10 μm in diameter is about 40 μm and the distance range to rod&cone cell surface is tens of micrometers, which varies from person to person. Therefore, determining reasonable capillary layer (CL) position in different human eyes is very difficult. In this paper, we propose a method to determine the position of retinal CL based on the rod&cone cell layer. The public positions of CL are recognized with 15 subjects from 40 to 59 years old, and the imaging planes of CL are calculated by the effective focal length of the human eye. High resolution retinal capillary imaging results obtained from 17 subjects with a liquid crystal adaptive optics system (LCAOS) validate our method. All of the subjects’ CLs have public positions from 127 μm to 147 μm from the rod&cone cell layer, which is influenced by the depth of focus. Project supported by the National Natural Science Foundation of China (Grant Nos. 11174274, 11174279, 61205021, 11204299, 61475152, and 61405194).

Variation in rod and cone density from the fovea to the mid-periphery in healthy human retinas using adaptive optics scanning laser ophthalmoscopy

PubMed Central

Wells-Gray, E M; Choi, S S; Bries, A; Doble, N

2016-01-01

Purpose To characterize the rod and cone photoreceptor mosaic at retinal locations spanning the central 60° in vivo using adaptive optics scanning laser ophthalmoscopy (AO-SLO) in healthy human eyes. Methods AO-SLO images (0.7 × 0.9°) were acquired at 680 nm from 14 locations from 30° nasal retina (NR) to 30° temporal retina (TR) in 5 subjects. Registered averaged images were used to measure rod and cone density and spacing within 60 × 60 μm regions of interest. Voronoi analysis was performed to examine packing geometry at all locations. Results Average peak cone density near the fovea was 164 000±24 000 cones/mm2 and decreased to 6700±1500 and 5400±700 cones/mm2 at 30° NR and 30° TR, respectively. Cone-to-cone spacing increased from 2.7±0.2 μm at the fovea to 14.6±1.4 μm at 30° NR and 16.3±0.7 μm at 30° TR. Rod density peaked at 25° NR (124 000±20 000 rods/mm2) and 20° TR (120 000±12 000 rods/mm2) and decreased at higher eccentricities. Center-to-center rod spacing was lowest nasally at 25° (2.1±0.1 μm). Temporally, rod spacing was lowest at 20° (2.2±0.1 μm) before increasing to 2.3±0.1 μm at 30° TR. Conclusions Both rod and cone densities showed good agreement with histology and prior AO-SLO studies. The results demonstrate the ability to image at higher retinal eccentricities than reported previously. This has clinical importance in diseases that initially affect the peripheral retina such as retinitis pigmentosa. PMID:27229708

A new species of salamander (Caudata: Plethodontidae, Bolitoglossa) from Sierra Nevada de Mérida, Venezuela.

PubMed

García-Gutiérrez, Javier; Escalona, Moisés; Mora, Andrés; Díaz De Pascual, Amelia; Fermin, Gustavo

2013-01-01

In this article, a new species of salamander of the genus Bolitoglossa (Eladinea) from the cloud forest near La Mucuy in Sierra Nevada de Mérida, Venezuelan Andes, is described. Bolitoglossa mucuyensis sp. nov. differs from all Venezuelan salamanders, except B. orestes, by a larger SVL/TL ratio, and from La Culata salamander B. orestes by a reduced webbing extension of the front and hind limbs. Additionally, B. mucuyensis sp. nov. and B. orestes diverge 3.12% in terms of the nucleotide sequence of the 16S rRNA gene, as previously reported, and in 8.1% for the cytb gene as shown in this study.

Informing recovery in a human-transformed landscape: Drought-mediated coexistence alters population trends of an imperiled salamander and invasive predators

USGS Publications Warehouse

Hossack, Blake R.; Honeycutt, Richard; Sigafus, Brent H.; Muths, Erin L.; Crawford, Catherine L.; Jones, Thomas R.; Sorensen, Jeff A.; Rorabaugh, James C.; Chambert, Thierry

2017-01-01

Understanding the additive or interactive threats of habitat transformation and invasive species is critical for conservation, especially where climate change is expected to increase the severity or frequency of drought. In the arid southwestern USA, this combination of stressors has caused widespread declines of native aquatic and semi-aquatic species. Achieving resilience to drought and other effects of climate change may depend upon continued management, so understanding the combined effects of stressors is important. We used Bayesian hierarchical models fitted with 10-years of pond-based monitoring surveys for the federally-endangered Sonoran Tiger Salamander (Ambystoma mavortium stebbinsi) and invasive predators (fishes and American Bullfrogs, Lithobates catesbeianus) that threaten native species. We estimated trends in occupancy of salamanders and invasive predators while accounting for hydrological dynamics of ponds, then used a two-species interaction model to directly estimate how invasive predators affected salamander occupancy. We also tested a conceptual model that predicted that drought, by limiting the distribution of invasive predators, could ultimately benefit native species. Even though occupancy of invasive predators was stationary and their presence in a pond reduced the probability of salamander presence by 23%, occupancy of Sonoran Tiger Salamanders increased, annually, by 2.2%. Occupancy of salamanders and invasive predators both declined dramatically following the 5th consecutive year of drought. Salamander occupancy recovered quickly after return to non-drought conditions, while occupancy of invasive predators remained suppressed. Models that incorporated three time-lagged periods (1 to 4 years) of local moisture conditions confirmed that salamanders and invasive predators responded differently to drought, reflecting how life-history strategies shape responses to disturbances. The positive 10-year trend in salamander occupancy and their

Loss of HCN1 enhances disease progression in mouse models of CNG channel-linked retinitis pigmentosa and achromatopsia.

PubMed

Schön, Christian; Asteriti, Sabrina; Koch, Susanne; Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Herms, Jochen; Seeliger, Mathias W; Cangiano, Lorenzo; Biel, Martin; Michalakis, Stylianos

2016-03-15

Most inherited blinding diseases are characterized by compromised retinal function and progressive degeneration of photoreceptors. However, the factors that affect the life span of photoreceptors in such degenerative retinal diseases are rather poorly understood. Here, we explore the role of hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) in this context. HCN1 is known to adjust retinal function under mesopic conditions, and although it is expressed at high levels in rod and cone photoreceptor inner segments, no association with any retinal disorder has yet been found. We investigated the effects of an additional genetic deletion of HCN1 on the function and survival of photoreceptors in a mouse model of CNGB1-linked retinitis pigmentosa (RP). We found that the absence of HCN1 in Cngb1 knockout (KO) mice exacerbated photoreceptor degeneration. The deleterious effect was reduced by expression of HCN1 using a viral vector. Moreover, pharmacological inhibition of HCN1 also enhanced rod degeneration in Cngb1 KO mice. Patch-clamp recordings revealed that the membrane potentials of Cngb1 KO and Cngb1/Hcn1 double-KO rods were both significantly depolarized. We also found evidence for altered calcium homeostasis and increased activation of the protease calpain in Cngb1/Hcn1 double-KO mice. Finally, the deletion of HCN1 also exacerbated degeneration of cone photoreceptors in a mouse model of CNGA3-linked achromatopsia. Our results identify HCN1 as a major modifier of photoreceptor degeneration and suggest that pharmacological inhibition of HCN channels may enhance disease progression in RP and achromatopsia patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Characterization of an Early-Onset, Autosomal Recessive, Progressive Retinal Degeneration in Bengal Cats.

PubMed

Ofri, Ron; Reilly, Christopher M; Maggs, David J; Fitzgerald, Paul G; Shilo-Benjamini, Yael; Good, Kathryn L; Grahn, Robert A; Splawski, Danielle D; Lyons, Leslie A

2015-08-01

A form of retinal degeneration suspected to be hereditary was discovered in a family of Bengal cats. A breeding colony was established to characterize disease progression clinically, electrophysiologically, and morphologically, and to investigate the mode of inheritance. Affected and related cats were donated by owners for breeding trials and pedigree analysis. Kittens from test and complementation breedings underwent ophthalmic and neuro-ophthalmic examinations and ERG, and globes were evaluated using light microscopy. Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats. Mutation analysis confirmed the disease is not caused by CEP290 or CRX variants found predominantly in Abyssinian and Siamese cats. Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks. Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration. A recessively inherited primary photoreceptor degeneration was characterized in the Bengal cat. The disease is characterized by early onset, with histologic, ophthalmoscopic, and electrophysiological signs evident by 2 months of age, and rapid progression to blindness.

Probing Mechanisms of Photoreceptor Degeneration in a New Mouse Model of the Common Form of Autosomal Dominant Retinitis Pigmentosa due to P23H Opsin Mutations*♦

PubMed Central

Sakami, Sanae; Maeda, Tadao; Bereta, Grzegorz; Okano, Kiichiro; Golczak, Marcin; Sumaroka, Alexander; Roman, Alejandro J.; Cideciyan, Artur V.; Jacobson, Samuel G.; Palczewski, Krzysztof

2011-01-01

Rhodopsin, the visual pigment mediating vision under dim light, is composed of the apoprotein opsin and the chromophore ligand 11-cis-retinal. A P23H mutation in the opsin gene is one of the most prevalent causes of the human blinding disease, autosomal dominant retinitis pigmentosa. Although P23H cultured cell and transgenic animal models have been developed, there remains controversy over whether they fully mimic the human phenotype; and the exact mechanism by which this mutation leads to photoreceptor cell degeneration remains unknown. By generating P23H opsin knock-in mice, we found that the P23H protein was inadequately glycosylated with levels 1–10% that of wild type opsin. Moreover, the P23H protein failed to accumulate in rod photoreceptor cell endoplasmic reticulum but instead disrupted rod photoreceptor disks. Genetically engineered P23H mice lacking the chromophore showed accelerated photoreceptor cell degeneration. These results indicate that most synthesized P23H protein is degraded, and its retinal cytotoxicity is enhanced by lack of the 11-cis-retinal chromophore during rod outer segment development. PMID:21224384

Good Epidemiologic Practice in Retinitis Pigmentosa: From Phenotyping to Biobanking

PubMed Central

Chizzolini, Marzio; Galan, Alessandro; Milan, Elisabeth; Sebastiani, Adolfo; Costagliola, Ciro; Parmeggiani, Francesco

2011-01-01

Inherited retinal dystrophies, such as retinitis pigmentosa (RP), include a group of relatively rare hereditary diseases caused by mutations in genes that code for proteins involved in the maintenance and function of the photoreceptor cells (cones and rods). The different forms of RP consist of progressive neurodegenerative disorders which are generally related to various and severe limitations of visual performances. In the course of typical RP (rod-cone dystrophy), the affected individuals first experience night-blindness and/or visual field constriction (secondary to rod dysfunctions), followed by variable alterations of the central vision (due to cone damages). On the other hand, during the atypical form of RP (cone-rod dystrophy), the cone’s functionalities are prevalently disrupted in comparison with the rod’s ones. The basic diagnosis of RP relies upon the documentation of unremitting loss in photoreceptor activity by electroretinogram and/or visual field testing. The prevalence of all RP typologies is variably reported in about one case for each 3000-5000 individuals, with a total of about two millions of affected persons worldwide. The inherited retinal dystrophies are sometimes the epiphenomenon of a complex framework (syndromic RP), but more often they represent an isolated disorder (about 85-90 % of cases). Although 200 causative RP mutations have been hitherto detected in more than 100 different genes, the molecular defect is identifiable in just about the 50% of the analyzed patients with RP. Not only the RP genotypes are very heterogeneous, but also the patients with the same mutation can be affected by different phenotypic manifestations. RP can be inherited as autosomal dominant, autosomal recessive or X-linked trait, and many sporadic forms are diagnosed in patients with no affected relatives. Dissecting the clinico-genetic complexity of RP has become an attainable objective by means of large-scale research projects, in which the collaboration

ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal.

PubMed

Quazi, Faraz; Molday, Robert S

2014-04-01

The visual cycle is a series of enzyme-catalyzed reactions which converts all-trans-retinal to 11-cis-retinal for the regeneration of visual pigments in rod and cone photoreceptor cells. Although essential for vision, 11-cis-retinal like all-trans-retinal is highly toxic due to its highly reactive aldehyde group and has to be detoxified by either reduction to retinol or sequestration within retinal-binding proteins. Previous studies have focused on the role of the ATP-binding cassette transporter ABCA4 associated with Stargardt macular degeneration and retinol dehydrogenases (RDH) in the clearance of all-trans-retinal from photoreceptors following photoexcitation. How rod and cone cells prevent the accumulation of 11-cis-retinal in photoreceptor disk membranes in excess of what is required for visual pigment regeneration is not known. Here we show that ABCA4 can transport N-11-cis-retinylidene-phosphatidylethanolamine (PE), the Schiff-base conjugate of 11-cis-retinal and PE, from the lumen to the cytoplasmic leaflet of disk membranes. This transport function together with chemical isomerization to its all-trans isomer and reduction to all-trans-retinol by RDH can prevent the accumulation of excess 11-cis-retinal and its Schiff-base conjugate and the formation of toxic bisretinoid compounds as found in ABCA4-deficient mice and individuals with Stargardt macular degeneration. This segment of the visual cycle in which excess 11-cis-retinal is converted to all-trans-retinol provides a rationale for the unusually high content of PE and its long-chain unsaturated docosahexaenoyl group in photoreceptor membranes and adds insight into the molecular mechanisms responsible for Stargardt macular degeneration.

Recapitulation of Human Retinal Development from Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors.

PubMed

Gonzalez-Cordero, Anai; Kruczek, Kamil; Naeem, Arifa; Fernando, Milan; Kloc, Magdalena; Ribeiro, Joana; Goh, Debbie; Duran, Yanai; Blackford, Samuel J I; Abelleira-Hervas, Laura; Sampson, Robert D; Shum, Ian O; Branch, Matthew J; Gardner, Peter J; Sowden, Jane C; Bainbridge, James W B; Smith, Alexander J; West, Emma L; Pearson, Rachael A; Ali, Robin R

2017-09-12

Transplantation of rod photoreceptors, derived either from neonatal retinae or pluripotent stem cells (PSCs), can restore rod-mediated visual function in murine models of inherited blindness. However, humans depend more upon cone photoreceptors that are required for daylight, color, and high-acuity vision. Indeed, macular retinopathies involving loss of cones are leading causes of blindness. An essential step for developing stem cell-based therapies for maculopathies is the ability to generate transplantable human cones from renewable sources. Here, we report a modified 2D/3D protocol for generating hPSC-derived neural retinal vesicles with well-formed ONL-like structures containing cones and rods bearing inner segments and connecting cilia, nascent outer segments, and presynaptic structures. This differentiation system recapitulates human photoreceptor development, allowing the isolation and transplantation of a pure population of stage-matched cones. Purified human long/medium cones survive and become incorporated within the adult mouse retina, supporting the potential of photoreceptor transplantation for treating retinal degeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.

PubMed

Nikopoulos, Konstantinos; Farinelli, Pietro; Giangreco, Basilio; Tsika, Chrysanthi; Royer-Bertrand, Beryl; Mbefo, Martial K; Bedoni, Nicola; Kjellström, Ulrika; El Zaoui, Ikram; Di Gioia, Silvio Alessandro; Balzano, Sara; Cisarova, Katarina; Messina, Andrea; Decembrini, Sarah; Plainis, Sotiris; Blazaki, Styliani V; Khan, Muhammad Imran; Micheal, Shazia; Boldt, Karsten; Ueffing, Marius; Moulin, Alexandre P; Cremers, Frans P M; Roepman, Ronald; Arsenijevic, Yvan; Tsilimbaris, Miltiadis K; Andréasson, Sten; Rivolta, Carlo

2016-09-01

Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A case for using Plethodontid salamanders for monitoring biodiversity and ecosystem integrity of North American forests

USGS Publications Warehouse

Welsh, H.H.; Droege, S.

2001-01-01

Terrestrial salamanders of the family P!ethodontidae have unique attributes that make them excellent indicators of biodiversity and ecosystem integrity in forested habitats. Their longevity, small territory size, site fidelity, sensitivity to natural and anthropogenic perturbations, tendency to occur in high densities, and low sampling costs mean that counts of plethodontid salamanders provide numerous advantages over counts of other North American forest organisms for indicating environmental change. Furthermore, they are tightly linked physiologically to microclimatic and successional processes that influence the distribution and abundance of numerous other hydrophilic but difficult-to-study forest-dwelling plants and animals. Ecosystem processes such as moisture cycling, food-web dynamics, and succession, with their related structural and microclimatic variability, all affect forest biodiversity and have been shown to affect salamander populations as well. We determined the variability associated with sampling for plethodontid salamanders by estimating the coefficient of variation (CV) from available time-series data. The median coefficient of variation indicated that variation in counts of individuals among studies was much lower in plethodonticis (27%) than in lepidoptera (93%), passerine birds (57%), small mammals (69%), or other amphibians (37-46%), which means plethodontid salamanders provide an important statistical advantage over other species for monitoring long-term forest health.

Coexistence in streams: Do source-sink dynamics allow salamanders to persist with fish predators?

USGS Publications Warehouse

Sepulveda, A.J.; Lowe, W.H.

2011-01-01

Theory suggests that source-sink dynamics can allow coexistence of intraguild predators and prey, but empirical evidence for this coexistence mechanism is limited. We used capture-mark-recapture, genetic methods, and stable isotopes to test whether source-sink dynamics promote coexistence between stream fishes, the intraguild predator, and stream salamanders (Dicamptodon aterrimus), the intraguild prey. Salamander populations from upstream reaches without fish were predicted to maintain or supplement sink populations in downstream reaches with fish. We found instead that downstream reaches with fish were not sinks even though fish consumed salamander larvae-apparent survival, recruitment, and population growth rate did not differ between upstream and downstream reaches. There was also no difference between upstream and downstream reaches in net emigration. We did find that D. aterrimus moved frequently along streams, but believe that this is a response to seasonal habitat changes rather than intraguild predation. Our study provides empirical evidence that local-scale mechanisms are more important than dispersal dynamics to coexistence of streams salamanders and fish. More broadly, it shows the value of empirical data on dispersal and gene flow for distinguishing between local and spatial mechanisms of coexistence. ?? 2011 Springer-Verlag.

[Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

PubMed

Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

2017-02-10

Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

Biallelic Variants in TTLL5, Encoding a Tubulin Glutamylase, Cause Retinal Dystrophy

PubMed Central

Sergouniotis, Panagiotis I.; Chakarova, Christina; Murphy, Cian; Becker, Mirjana; Lenassi, Eva; Arno, Gavin; Lek, Monkol; MacArthur, Daniel G.; Bhattacharya, Shomi S.; Moore, Anthony T.; Holder, Graham E.; Robson, Anthony G.; Wolfrum, Uwe; Webster, Andrew R.; Plagnol, Vincent

2014-01-01

In a subset of inherited retinal degenerations (including cone, cone-rod, and macular dystrophies), cone photoreceptors are more severely affected than rods; ABCA4 mutations are the most common cause of this heterogeneous class of disorders. To identify retinal-disease-associated genes, we performed exome sequencing in 28 individuals with “cone-first” retinal disease and clinical features atypical for ABCA4 retinopathy. We then conducted a gene-based case-control association study with an internal exome data set as the control group. TTLL5, encoding a tubulin glutamylase, was highlighted as the most likely disease-associated gene; 2 of 28 affected subjects harbored presumed loss-of-function variants: c.[1586_1589delAGAG];[1586_1589delAGAG], p.[Glu529Valfs∗2];[Glu529Valfs∗2], and c.[401delT(;)3354G>A], p.[Leu134Argfs∗45(;)Trp1118∗]. We then inspected previously collected exome sequence data from individuals with related phenotypes and found two siblings with homozygous nonsense variant c.1627G>T (p.Glu543∗) in TTLL5. Subsequently, we tested a panel of 55 probands with retinal dystrophy for TTLL5 mutations; one proband had a homozygous missense change (c.1627G>A [p.Glu543Lys]). The retinal phenotype was highly similar in three of four families; the sibling pair had a more severe, early-onset disease. In human and murine retinae, TTLL5 localized to the centrioles at the base of the connecting cilium. TTLL5 has been previously reported to be essential for the correct function of sperm flagella in mice and play a role in polyglutamylation of primary cilia in vitro. Notably, genes involved in the polyglutamylation and deglutamylation of tubulin have been associated with photoreceptor degeneration in mice. The electrophysiological and fundus autofluorescence imaging presented here should facilitate the molecular diagnosis in further families. PMID:24791901

Clinical Characteristics and Current Therapies for Inherited Retinal Degenerations

PubMed Central

Sahel, José-Alain; Marazova, Katia; Audo, Isabelle

2015-01-01

Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307–316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod–cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone–rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances. PMID:25324231

NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP).

PubMed

Schorderet, Daniel F; Escher, Pascal

2009-11-01

NR2E3, also called photoreceptor-specific nuclear receptor (PNR), is a transcription factor of the nuclear hormone receptor superfamily whose expression is uniquely restricted to photoreceptors. There, its physiological activity is essential for proper rod and cone photoreceptor development and maintenance. Thirty-two different mutations in NR2E3 have been identified in either homozygous or compound heterozygous state in the recessively inherited enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), and clumped pigmentary retinal degeneration (CPRD). The clinical phenotype common to all these patients is night blindness, rudimental or absent rod function, and hyperfunction of the "blue" S-cones. A single p.G56R mutation is inherited in a dominant manner and causes retinitis pigmentosa (RP). We have established a new locus-specific database for NR2E3 (www.LOVD.nl/eye), containing all reported mutations, polymorphisms, and unclassified sequence variants, including novel ones. A high proportion of mutations are located in the evolutionarily-conserved DNA-binding domains (DBDs) and ligand-binding domains (LBDs) of NR2E3. Based on homology modeling of these NR2E3 domains, we propose a structural localization of mutated residues. The high variability of clinical phenotypes observed in patients affected by NR2E3-linked retinal degenerations may be caused by different disease mechanisms, including absence of DNA-binding, altered interactions with transcriptional coregulators, and differential activity of modifier genes.

Better than fish on land? Hearing across metamorphosis in salamanders.

PubMed

Christensen, Christian Bech; Lauridsen, Henrik; Christensen-Dalsgaard, Jakob; Pedersen, Michael; Madsen, Peter Teglberg

2015-03-07

Early tetrapods faced an auditory challenge from the impedance mismatch between air and tissue in the transition from aquatic to terrestrial lifestyles during the Early Carboniferous (350 Ma). Consequently, tetrapods may have been deaf to airborne sounds for up to 100 Myr until tympanic middle ears evolved during the Triassic. The middle ear morphology of recent urodeles is similar to that of early 'lepospondyl' microsaur tetrapods, and experimental studies on their hearing capabilities are therefore useful to understand the evolutionary and functional drivers behind the shift from aquatic to aerial hearing in early tetrapods. Here, we combine imaging techniques with neurophysiological measurements to resolve how the change from aquatic larvae to terrestrial adult affects the ear morphology and sensory capabilities of salamanders. We show that air-induced pressure detection enhances underwater hearing sensitivity of salamanders at frequencies above 120 Hz, and that both terrestrial adults and fully aquatic juvenile salamanders can detect airborne sound. Collectively, these findings suggest that early atympanic tetrapods may have been pre-equipped to aerial hearing and are able to hear airborne sound better than fish on land. When selected for, this rudimentary hearing could have led to the evolution of tympanic middle ears. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Evolutionary history of a complex adaptation: Tetrodotoxin resistance in salamanders

PubMed Central

Hanifin, Charles T.; Gilly, William F.

2017-01-01

Understanding the processes that generate novel adaptive phenotypes is central to evolutionary biology. We used comparative analyses to reveal the history of tetrodotoxin (TTX) resistance in TTX-bearing salamanders. Resistance to TTX is a critical component of the ability to use TTX defensively but the origin of the TTX-bearing phenotype is unclear. Skeletal muscle of TTX-bearing salamanders (modern newts, family: Salamandridae) is unaffected by TTX at doses far in excess of those that block action potentials in muscle and nerve of other vertebrates. Skeletal muscle of non-TTX-bearing salamandrids is also resistant to TTX but at lower levels. Skeletal muscle TTX resistance in the Salamandridae results from the expression of TTX-resistant variants of the voltage-gated sodium channel NaV 1.4 (SCN4a). We identified four substitutions in the coding region of salSCN4a that are likely responsible for the TTX resistance measured in TTX-bearing salamanders and variation at one of these sites likely explains variation in TTX resistance among other lineages. Our results suggest that exaptation has played a role in the evolution of the TTX-bearing phenotype and provide empirical evidence that complex physiological adaptations can arise through the accumulation of beneficial mutations in the coding region of conserved proteins. PMID:25346116

Comparative and developmental patterns of amphibious auditory function in salamanders.

PubMed

Zeyl, Jeffrey N; Johnston, Carol E

2016-12-01

Early amphibious tetrapods may have detected aquatic sound pressure using sound-induced lung vibrations, but their lack of tympanic middle ears would have restricted aerial sensitivity. Sharing these characteristics, salamanders could be models for the carryover of auditory function across an aquatic-terrestrial boundary without tympanic middle ears. We measured amphibious auditory evoked potential audiograms in five phylogenetically and ecologically distinct salamanders (Amphiuma means, Notophthalmus viridescens, Ambystoma talpoideum, Eurycea spp., and Plethodon glutinosus) and tested whether metamorphosis and terrestrial niche were linked to aerial sensitivity. Threshold differences between media varied between species. A. means' relative aerial sensitivity was greatest at 100 Hz and decreased with increasing frequency. In contrast, all other salamanders retained greater sensitivity up to 500 Hz, and in A. talpoideum and Eurycea, relative sensitivity at 500 Hz was higher than at 100 Hz. Aerial thresholds of terrestrial P. glutinosus above 200 Hz were similar to A. talpoideum and Eurycea, but lower than N. viridescens and A. means. Metamorphosis did not affect aerial sensitivity in N. viridescens or A. talpoideum. These results fail to support a hypothesis of terrestrial hearing specialization across ontogeny or phylogeny. We discuss methodological limitations to our amphibious comparisons and factors affecting variation in amphibious performance.

High-speed adaptive optics line scan confocal retinal imaging for human eye.

PubMed

Lu, Jing; Gu, Boyu; Wang, Xiaolin; Zhang, Yuhua

2017-01-01

Continuous and rapid eye movement causes significant intraframe distortion in adaptive optics high resolution retinal imaging. To minimize this artifact, we developed a high speed adaptive optics line scan confocal retinal imaging system. A high speed line camera was employed to acquire retinal image and custom adaptive optics was developed to compensate the wave aberration of the human eye's optics. The spatial resolution and signal to noise ratio were assessed in model eye and in living human eye. The improvement of imaging fidelity was estimated by reduction of intra-frame distortion of retinal images acquired in the living human eyes with frame rates at 30 frames/second (FPS), 100 FPS, and 200 FPS. The device produced retinal image with cellular level resolution at 200 FPS with a digitization of 512×512 pixels/frame in the living human eye. Cone photoreceptors in the central fovea and rod photoreceptors near the fovea were resolved in three human subjects in normal chorioretinal health. Compared with retinal images acquired at 30 FPS, the intra-frame distortion in images taken at 200 FPS was reduced by 50.9% to 79.7%. We demonstrated the feasibility of acquiring high resolution retinal images in the living human eye at a speed that minimizes retinal motion artifact. This device may facilitate research involving subjects with nystagmus or unsteady fixation due to central vision loss.

Parenteral Lipid Dose Restriction With Soy Oil, Not Fish Oil, Preserves Retinal Function in Neonatal Piglets.

PubMed

Lansing, Marihan; Sauvé, Yves; Dimopoulos, Ioannis; Field, Catherine J; Suh, Miyoung; Wizzard, Pamela; Goruk, Susan; Lim, David; Muto, Mitsuru; Wales, Paul; Turner, Justine

2018-03-13

A dietary supply of docosahexaenoic acid (DHA) and arachidonic acid (AA) is critical for neonatal retinal development. Both are absent/minimal in parenteral nutrition (PN) using soy-oil emulsions ([SO] Intralipid®) traditionally used for neonatal intestinal failure. In contrast, fish-oil emulsions ([FO] Omegaven®) are enriched in DHA/AA. The aim of this study was to compare retinal function and fatty acid content in neonatal piglets fed PN with SO or FO. Two-5-day-old piglets were randomly allocated to SO (n = 4) or FO (n = 4), provided at equivalent doses (5g/kg/d). After 14 days of PN, retinal function was assessed by electroretinography and retinas were harvested for fatty acid content analysis. Sow-fed piglets served as a reference (REF). Light flash-elicited stoppage of cone and rod dark-currents (a-waves) and the ensuing postsynaptic activation of cone and rod ON bipolar cells (b-waves) were comparable between SO and REF. Responses recorded from FO were subnormal (P <0.001) when compared with both SO and REF. Retinal DHA content was similar in both groups (FO, 14.59% vs SO, 12.22%; P = 0.32); while AA was lower in FO (FO, 6.01% vs SO, 8.21%; P = .001). Paradoxically, FO containing more DHA and AA did not preserve retinal function when compared with the same low dose of SO. This may be due to the reduced AA enrichment in the retina with FO treatment. Further investigation into the ideal amounts of DHA and AA for optimal neonatal retinal function is required. © 2018 American Society for Parenteral and Enteral Nutrition.

Transcriptional and phylogenetic analysis of five complete ambystomatid salamander mitochondrial genomes.

PubMed

Samuels, Amy K; Weisrock, David W; Smith, Jeramiah J; France, Katherine J; Walker, John A; Putta, Srikrishna; Voss, S Randal

2005-04-11

We report on a study that extended mitochondrial transcript information from a recent EST project to obtain complete mitochondrial genome sequence for 5 tiger salamander complex species (Ambystoma mexicanum, A. t. tigrinum, A. andersoni, A. californiense, and A. dumerilii). We describe, for the first time, aspects of mitochondrial transcription in a representative amphibian, and then use complete mitochondrial sequence data to examine salamander phylogeny at both deep and shallow levels of evolutionary divergence. The available mitochondrial ESTs for A. mexicanum (N=2481) and A. t. tigrinum (N=1205) provided 92% and 87% coverage of the mitochondrial genome, respectively. Complete mitochondrial sequences for all species were rapidly obtained by using long distance PCR and DNA sequencing. A number of genome structural characteristics (base pair length, base composition, gene number, gene boundaries, codon usage) were highly similar among all species and to other distantly related salamanders. Overall, mitochondrial transcription in Ambystoma approximated the pattern observed in other vertebrates. We inferred from the mapping of ESTs onto mtDNA that transcription occurs from both heavy and light strand promoters and continues around the entire length of the mtDNA, followed by post-transcriptional processing. However, the observation of many short transcripts corresponding to rRNA genes indicates that transcription may often terminate prematurely to bias transcription of rRNA genes; indeed an rRNA transcription termination signal sequence was observed immediately following the 16S rRNA gene. Phylogenetic analyses of salamander family relationships consistently grouped Ambystomatidae in a clade containing Cryptobranchidae and Hynobiidae, to the exclusion of Salamandridae. This robust result suggests a novel alternative hypothesis because previous studies have consistently identified Ambystomatidae and Salamandridae as closely related taxa. Phylogenetic analyses of tiger

Differentiation of Swine iPSC into Rod Photoreceptors and Their Integration into the Retina

PubMed Central

Zhou, Liang; Wang, Wei; Liu, Yongqing; de Castro, Juan Fernandez; Ezashi, Toshihiko; Telugu, Bhanu Prakash V.L.; Roberts, R. Michael; Kaplan, Henry J.; Dean, Douglas C.

2014-01-01

Absence of a regenerative pathway for damaged retina following injury or disease has led to experiments utilizing stem cell transplantation for retinal repair, and encouraging results have been obtained in rodents. The swine eye is a closer anatomical and physiological match to the human eye, but embryonic stem cells have not been isolated from pig, and photoreceptor differentiation has not been demonstrated with swine induced pluripotent stem cells (iPSC). Here, we subjected swine iPSC to a rod photoreceptor differentiation protocol consisting of floating culture as embryoid bodies followed by differentiation in adherent culture. Real time PCR and immunostaining of differentiated cells demonstrated loss of expression of the pluripotent genes POU5F1, NANOG and SOX2 and induction of rod photoreceptor genes RCVRN, NRL, RHO and ROM1. While these differentiated cells displayed neuronal morphology, culturing on a Matrigel substratum triggered a further morphological change resulting in concentration of RHO and ROM1 in outer segment-like projections resembling those on primary cultures of rod photoreceptors. The differentiated cells were transplanted into the subretinal space of pigs treated with iodoacetic acid to eliminate rod photoreceptors. Three weeks after transplantation, engrafted RHO+ cells were evident in the outer nuclear layer where photoreceptors normally reside. A portion of these transplanted cells had generated projections resembling outer segments. These results demonstrate that swine iPSC can differentiate into photoreceptors in culture and these cells can integrate into the damaged swine neural retina thus laying a foundation for future studies using the pig as a model for retinal stem cell transplantation. PMID:21491544

Cone Structure in Retinal Degeneration Associated with Mutations in the peripherin/RDS Gene

PubMed Central

Talcott, Katherine E.; Ratnam, Kavitha; Sundquist, Sanna M.; Lucero, Anya S.; Day, Shelley; Zhang, Yuhua; Roorda, Austin

2011-01-01

Purpose. To study cone photoreceptor structure and function associated with mutations in the second intradiscal loop region of peripherin/RDS. Methods. High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in four patients with peripherin/RDS mutations and 27 age-similar healthy subjects. Measures of retinal structure and fundus autofluorescence (AF) were correlated with visual function, including best-corrected visual acuity (BCVA), kinetic and static perimetry, fundus-guided microperimetry, full-field electroretinography (ERG), and multifocal ERG. The coding regions of the peripherin/RDS gene were sequenced in each patient. Results. Heterozygous mutations in peripherin/RDS were predicted to affect protein structure in the second intradiscal domain in each patient (Arg172Trp, Gly208Asp, Pro210Arg and Cys213Tyr). BCVA was at least 20/32 in the study eye of each patient. Diffuse cone-greater-than-rod dysfunction was present in patient 1, while rod-greater-than-cone dysfunction was present in patient 4; macular outer retinal dysfunction was present in all patients. Macular AF was heterogeneous, and the photoreceptor-retinal pigment epithelial (RPE) junction layer showed increased reflectivity at the fovea in all patients except patient 1, who showed cone-rod dystrophy. Cone packing was irregular, and cone spacing was significantly increased (z-scores >2) at most locations throughout the central 4° in each patient. Conclusions. peripherin/RDS mutations produced diffuse AF abnormalities, disruption of the photoreceptor/RPE junction, and increased cone spacing, consistent with cone loss in the macula. The abnormalities observed suggest that the integrity of the second intradiscal domain of peripherin/RDS is critical for normal macular cone structure. PMID:21071739

Force dependence of phagosome trafficking in retinal pigment epithelial cells

NASA Astrophysics Data System (ADS)

Daniel, Rebekah; Koll, Andrew T.; Altman, David

2014-09-01

Retinal pigment epithelial (RPE) cells play an integral role in the renewal of photoreceptor disk membranes. As rod and cone cells shed their outer segments, they are phagocytosed and degraded by the RPE, and a failure in this process can result in retinal degeneration. We have studied the role of myosin VI in nonspecific phagocytosis in a human RPE primary cell line (ARPE-19), testing the hypothesis that this motor generates the forces required to traffic phagosomes in these cells. Experiments were conducted in the presence of forces through the use of in vivo optical trapping. Our results support a role for myosin VI in phagosome trafficking and demonstrate that applied forces modulate rates of phagosome trafficking.

Abundances of northwestern salamander larvae in montane lakes with and without fish, Mount Rainier National Park, Washington

USGS Publications Warehouse

Larson, Gary L.; Hoffman, Robert L.

2002-01-01

In Mount Rainier National Park, the northwestern salamander usually inhabits relatively large and deep lakes and ponds (average size = 0.3 ha; average depth > 2 m) that contain flocculent, organic bottom sediments and abundant coarse wood. Prior to 1970, salmonids were introduced into many of the park's lakes and ponds that were typical habitat of the northwestern salamander. The objective of this study was to compare, in lakes and ponds with suitable habitat characteristics for northwestern salamanders, the observed abundances of larvae in takes and ponds with and without these introduced salmonids. Day surveys of 61 lakes were conducted between 1993 and 1999. Fish were limited to takes and ponds deeper than 2 in. For the 48 lakes and ponds deeper than 2 in (i.e., 25 fishless lakes and 23 fish lakes), the mean and median observed abundances of northwestern salamander larvae in fishless lakes and ponds was significantly greater than the mean and median observed abundances of larvae in lakes and ponds with fish. Northwestern salamander larvae were not observed in 11 fish lakes. These lakes were similar in median elevation, surface area, and maximum depth to the fishless lakes. The 12 fish lakes with observed larvae were significantly lower in median elevation, larger in median surface area, and deeper in median maximum depth than the fishless lakes. Low to null observed abundances of northwestern salamander larvae in lakes and ponds with fish were attributed to a combination of fish predation of larvae and changes in larval behavior.

Samd7 is a cell type-specific PRC1 component essential for establishing retinal rod photoreceptor identity

PubMed Central

Omori, Yoshihiro; Kubo, Shun; Kon, Tetsuo; Furuhashi, Mayu; Narita, Hirotaka; Kominami, Taro; Ueno, Akiko; Tsutsumi, Ryotaro; Chaya, Taro; Yamamoto, Haruka; Suetake, Isao; Ueno, Shinji; Koseki, Haruhiko; Furukawa, Takahisa

2017-01-01

Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells. Samd7-null mutant mice showed ectopic expression of nonrod genes including S-opsin in rod photoreceptor cells and rod photoreceptor cell dysfunction. Samd7 physically interacts with Polyhomeotic homologs (Phc proteins), components of the Polycomb repressive complex 1 (PRC1), and colocalizes with Phc2 and Ring1B in Polycomb bodies. ChIP assays showed a significant decrease of H3K27me3 in the genes up-regulated in the Samd7-deficient retina, showing that Samd7 deficiency causes the derepression of nonrod gene expression in rod photoreceptor cells. The current study suggests that Samd7 is a cell type-specific PRC1 component epigenetically defining rod photoreceptor cell identity. PMID:28900001

Samd7 is a cell type-specific PRC1 component essential for establishing retinal rod photoreceptor identity.

PubMed

Omori, Yoshihiro; Kubo, Shun; Kon, Tetsuo; Furuhashi, Mayu; Narita, Hirotaka; Kominami, Taro; Ueno, Akiko; Tsutsumi, Ryotaro; Chaya, Taro; Yamamoto, Haruka; Suetake, Isao; Ueno, Shinji; Koseki, Haruhiko; Nakagawa, Atsushi; Furukawa, Takahisa

2017-09-26

Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells. Samd7- null mutant mice showed ectopic expression of nonrod genes including S-opsin in rod photoreceptor cells and rod photoreceptor cell dysfunction. Samd7 physically interacts with Polyhomeotic homologs (Phc proteins), components of the Polycomb repressive complex 1 (PRC1), and colocalizes with Phc2 and Ring1B in Polycomb bodies. ChIP assays showed a significant decrease of H3K27me3 in the genes up-regulated in the Samd7 -deficient retina, showing that Samd7 deficiency causes the derepression of nonrod gene expression in rod photoreceptor cells. The current study suggests that Samd7 is a cell type-specific PRC1 component epigenetically defining rod photoreceptor cell identity.

Variable infection of stream salamanders in the southern Appalachians by the trematode Metagonimoides oregonensis (family: Heterophyidae)

Treesearch

Jennie A. Wyderko; Ernest F. Benfield; John C. Maerz; Kristen C. Cecala; Lisa K. Belden

2015-01-01

Many factors contribute to parasites varying in host specificity and distribution among potential hosts. Metagonimoides oregonensis is a digenetic trematode that uses stream-dwelling plethodontid salamanders as second intermediate hosts in the Eastern US. We completed a field survey to identify which stream salamander species, at a regional level, are most...

Cell Death Pathways in Mutant Rhodopsin Rat Models Identifies Genotype-Specific Targets Controlling Retinal Degeneration.

PubMed

Viringipurampeer, Ishaq A; Gregory-Evans, Cheryl Y; Metcalfe, Andrew L; Bashar, Emran; Moritz, Orson L; Gregory-Evans, Kevin

2018-06-18

Retinitis pigmentosa (RP) is a group of inherited neurological disorders characterized by rod photoreceptor cell death, followed by secondary cone cell death leading to progressive blindness. Currently, there are no viable treatment options for RP. Due to incomplete knowledge of the molecular signaling pathways associated with RP pathogenesis, designing therapeutic strategies remains a challenge. In particular, preventing secondary cone photoreceptor cell loss is a key goal in designing potential therapies. In this study, we identified the main drivers of rod cell death and secondary cone loss in the transgenic S334ter rhodopsin rat model, tested the efficacy of specific cell death inhibitors on retinal function, and compared the effect of combining drugs to target multiple pathways in the S334ter and P23H rhodopsin rat models. The primary driver of early rod cell death in the S334ter model was a caspase-dependent process, whereas cone cell death occurred though RIP3-dependent necroptosis. In comparison, rod cell death in the P23H model was via necroptotic signaling, whereas cone cell loss occurred through inflammasome activation. Combination therapy of four drugs worked better than the individual drugs in the P23H model but not in the S334ter model. These differences imply that treatment modalities need to be tailored for each genotype. Taken together, our data demonstrate that rationally designed genotype-specific drug combinations will be an important requisite to effectively target primary rod cell loss and more importantly secondary cone survival.

Characterization of an Early-Onset, Autosomal Recessive, Progressive Retinal Degeneration in Bengal Cats

PubMed Central

Ofri, Ron; Reilly, Christopher M.; Maggs, David J.; Fitzgerald, Paul G.; Shilo-Benjamini, Yael; Good, Kathryn L.; Grahn, Robert A.; Splawski, Danielle D.; Lyons, Leslie A.

2015-01-01

Purpose A form of retinal degeneration suspected to be hereditary was discovered in a family of Bengal cats. A breeding colony was established to characterize disease progression clinically, electrophysiologically, and morphologically, and to investigate the mode of inheritance. Methods Affected and related cats were donated by owners for breeding trials and pedigree analysis. Kittens from test and complementation breedings underwent ophthalmic and neuro-ophthalmic examinations and ERG, and globes were evaluated using light microscopy. Results Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats. Mutation analysis confirmed the disease is not caused by CEP290 or CRX variants found predominantly in Abyssinian and Siamese cats. Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks. Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration. Conclusions A recessively inherited primary photoreceptor degeneration was characterized in the Bengal cat. The disease is characterized by early onset, with histologic, ophthalmoscopic, and electrophysiological signs evident by 2 months of age, and rapid progression to blindness. PMID:26258614

Effects of microhabitat and large-scale land use on stream salamander occupancy in the coalfields of Central Appalachia

USGS Publications Warehouse

Sweeten, Sara E.; Ford, W. Mark

2016-01-01

Large-scale coal mining practices, particularly surface coal extraction and associated valley fills as well as residential wastewater discharge, are of ecological concern for aquatic systems in central Appalachia. Identifying and quantifying alterations to ecosystems along a gradient of spatial scales is a necessary first-step to aid in mitigation of negative consequences to aquatic biota. In central Appalachian headwater streams, apart from fish, salamanders are the most abundant vertebrate predator that provide a significant intermediate trophic role linking aquatic and terrestrial food webs. Stream salamander species are considered to be sensitive to aquatic stressors and environmental alterations, as past research has shown linkages among microhabitat parameters, large-scale land use such as urbanization and logging, and salamander abundances. However, there is little information examining these relationships between environmental conditions and salamander occupancy in the coalfields of central Appalachia. In the summer of 2013, 70 sites (sampled two to three times each) in the southwest Virginia coalfields were visited to collect salamanders and quantify stream and riparian microhabitat parameters. Using an information-theoretic framework, effects of microhabitat and large-scale land use on stream salamander occupancy were compared. The findings indicate that Desmognathus spp. occupancy rates are more correlated to microhabitat parameters such as canopy cover than to large-scale land uses. However, Eurycea spp. occupancy rates had a strong association with large-scale land uses, particularly recent mining and forest cover within the watershed. These findings suggest that protection of riparian habitats is an important consideration for maintaining aquatic systems in central Appalachia. If this is not possible, restoration riparian areas should follow guidelines using quick-growing tree species that are native to Appalachian riparian areas. These types of trees

Pattern of retinal morphological and functional decay in a light-inducible, rhodopsin mutant mouse.

PubMed

Gargini, Claudia; Novelli, Elena; Piano, Ilaria; Biagioni, Martina; Strettoi, Enrica

2017-07-18

Hallmarks of Retinitis Pigmentosa (RP), a family of genetic diseases, are a typical rod-cone-degeneration with initial night blindness and loss of peripheral vision, followed by decreased daylight sight and progressive visual acuity loss up to legal blindness. Great heterogeneity in nature and function of mutated genes, variety of mutations for each of them, variability in phenotypic appearance and transmission modality contribute to make RP a still incurable disease. Translational research relies on appropriate animal models mimicking the genetic and phenotypic diversity of the human pathology. Here, we provide a systematic, morphological and functional analysis of Rho Tvrm4 /Rho + rhodopsin mutant mice, originally described in 2010 and portraying several features of common forms of autosomal dominant RP caused by gain-of-function mutations. These mice undergo photoreceptor degeneration only when exposed briefly to strong, white light and allow controlled timing of induction of rod and cone death, which therefore can be elicited in adult animals, as observed in human RP. The option to control severity and retinal extent of the phenotype by regulating intensity and duration of the inducing light opens possibilities to exploit this model for multiple experimental purposes. Altogether, the unique features of this mutant make it an excellent resource for retinal degeneration research.

Altered Expression of Retinal Molecular Markers in the Canine RPE65 Model of Leber Congenital Amaurosis

PubMed Central

Hernández, Maria; Pearce-Kelling, Susan E.; Rodriguez, F. David; Aguirre, Gustavo D.; Vecino, Elena

2010-01-01

Purpose. Leber congenital amaurosis (LCA) is a group of childhood-onset retinal diseases characterized by severe visual impairment or blindness. One form is caused by mutations in the RPE65 gene, which encodes the retinal pigment epithelium (RPE) isomerase. In this study, the retinal structure and expression of molecular markers for different retinal cell types were characterized, and differences between control and RPE65 mutant dogs during the temporal evolution of the disease were analyzed. Methods. Retinas from normal and mutant dogs of different ages were examined by immunofluorescence with a panel of 16 different antibodies. Results. Cones and rods were preserved in the mutant retinas, and the number of cones was normal. However, there was altered expression of cone arrestin and delocalization of rod opsin. The ON bipolar cells showed sprouting of the dendritic arbors toward the outer nuclear layer (ONL) and retraction of their axons in the inner nuclear layer (INL). A decreased expression of GABA, and an increased expression of intermediate filament glial markers was also found in the mutant retinas. These changes were more evident in the adult than the young mutant retinas. Conclusions. The structure of the retina is well preserved in the mutant retina, but several molecular changes take place in photoreceptors and in bipolar and amacrine cells. Some of these changes are structural, whereas others reflect a change in localization of the examined proteins. This study provides new information that can be applied to the interpretation of outcomes of retinal gene therapy in animal models and humans. PMID:20671290

Melanopsin changes in neonatal albino rat independent of rods and cones.

PubMed

Hannibal, Jens; Georg, Birgitte; Fahrenkrug, Jan

2007-01-08

Intrinsically photosensitive retinal ganglion cells employ the photopigment melanopsin and provide light information to brain areas responsible for the regulation of circadian rhythms. The expression of melanopsin is regulated by environmental illumination, but it remains to be clarified whether the rods and cones are involved. Here, we examined the influence of 5 days of constant light and dark conditions on melanopsin mRNA and protein expression in newborn albino rats, in which functional rods and cones have not yet been developed. We found that the melanopsin mRNA level was unaffected, whereas the melanopsin protein level was more than two-fold higher in the darkness-adapted group than in pups raised in constant light. In pups raised during 12 : 12 h light/dark cycles, the melanopsin protein level was significantly higher during the day than at night. Our findings indicate that melanopsin protein changes are independent of input from the rods and cones.

Bifurcation analysis of a photoreceptor interaction model for Retinitis Pigmentosa

NASA Astrophysics Data System (ADS)

Camacho, Erika T.; Radulescu, Anca; Wirkus, Stephen

2016-09-01

Retinitis Pigmentosa (RP) is the term used to describe a diverse set of degenerative eye diseases affecting the photoreceptors (rods and cones) in the retina. This work builds on an existing mathematical model of RP that focused on the interaction of the rods and cones. We non-dimensionalize the model and examine the stability of the equilibria. We then numerically investigate other stable modes that are present in the system for various parameter values and relate these modes to the original problem. Our results show that stable modes exist for a wider range of parameter values than the stability of the equilibrium solutions alone, suggesting that additional approaches to preventing cone death may exist.

A Salamander Tale: Effective Exhibits and Attitude Change

ERIC Educational Resources Information Center

Rollins, Jeffrey; Watson, Sunnie Lee

2017-01-01

Little information exists regarding intention behind the design and development of Extension outreach and educational exhibits. An evaluation of response to the exhibit "A Salamander Tale" indicates that the methods used to develop the exhibit resulted in an effective way to present information to an adult audience. Survey questions were…

Low levels of LTR retrotransposon deletion by ectopic recombination in the gigantic genomes of salamanders.

PubMed

Frahry, Matthew Blake; Sun, Cheng; Chong, Rebecca A; Mueller, Rachel Lockridge

2015-02-01

Across the tree of life, species vary dramatically in nuclear genome size. Mutations that add or remove sequences from genomes-insertions or deletions, or indels-are the ultimate source of this variation. Differences in the tempo and mode of insertion and deletion across taxa have been proposed to contribute to evolutionary diversity in genome size. Among vertebrates, most of the largest genomes are found within the salamanders, an amphibian clade with genome sizes ranging from ~14 to ~120 Gb. Salamander genomes have been shown to experience slower rates of DNA loss through small (i.e., <30 bp) deletions than do other vertebrate genomes. However, no studies have addressed DNA loss from salamander genomes resulting from larger deletions. Here, we focus on one type of large deletion-ectopic-recombination-mediated removal of LTR retrotransposon sequences. In ectopic recombination, double-strand breaks are repaired using a "wrong" (i.e., ectopic, or non-allelic) template sequence-typically another locus of similar sequence. When breaks occur within the LTR portions of LTR retrotransposons, ectopic-recombination-mediated repair can produce deletions that remove the internal transposon sequence and the equivalent of one of the two LTR sequences. These deletions leave a signature in the genome-a solo LTR sequence. We compared levels of solo LTRs in the genomes of four salamander species with levels present in five vertebrates with smaller genomes. Our results demonstrate that salamanders have low levels of solo LTRs, suggesting that ectopic-recombination-mediated deletion of LTR retrotransposons occurs more slowly than in other vertebrates with smaller genomes.

Multiple rod–cone and cone–rod photoreceptor transmutations in snakes: Evidence from visual opsin gene expression

USGS Publications Warehouse

Simoe, Bruno F; Sampaio, Filipa L.; Loew, Ellis R.; Sanders, Kate L.; Fisher, Robert N.; Hart, Nathan S.; Hunt, David M.; Partridge, Julian C.; Gower, David J.

2016-01-01

In 1934, Gordon Walls forwarded his radical theory of retinal photoreceptor ‘transmutation’. This proposed that rods and cones used for scotopic and photopic vision, respectively, were not fixed but could evolve into each other via a series of morphologically distinguishable intermediates. Walls' prime evidence came from series of diurnal and nocturnal geckos and snakes that appeared to have pure-cone or pure-rod retinas (in forms that Walls believed evolved from ancestors with the reverse complement) or which possessed intermediate photoreceptor cells. Walls was limited in testing his theory because the precise identity of visual pigments present in photoreceptors was then unknown. Subsequent molecular research has hitherto neglected this topic but presents new opportunities. We identify three visual opsin genes, rh1, sws1 and lws, in retinal mRNA of an ecologically and taxonomically diverse sample of snakes central to Walls' theory. We conclude that photoreceptors with superficially rod- or cone-like morphology are not limited to containing scotopic or photopic opsins, respectively. Walls' theory is essentially correct, and more research is needed to identify the patterns, processes and functional implications of transmutation. Future research will help to clarify the fundamental properties and physiology of photoreceptors adapted to function in different light levels.

Multiple rod–cone and cone–rod photoreceptor transmutations in snakes: evidence from visual opsin gene expression

PubMed Central

Sampaio, Filipa L.; Loew, Ellis R.; Sanders, Kate L.; Fisher, Robert N.; Hart, Nathan S.; Hunt, David M.; Partridge, Julian C.

2016-01-01

In 1934, Gordon Walls forwarded his radical theory of retinal photoreceptor ‘transmutation’. This proposed that rods and cones used for scotopic and photopic vision, respectively, were not fixed but could evolve into each other via a series of morphologically distinguishable intermediates. Walls' prime evidence came from series of diurnal and nocturnal geckos and snakes that appeared to have pure-cone or pure-rod retinas (in forms that Walls believed evolved from ancestors with the reverse complement) or which possessed intermediate photoreceptor cells. Walls was limited in testing his theory because the precise identity of visual pigments present in photoreceptors was then unknown. Subsequent molecular research has hitherto neglected this topic but presents new opportunities. We identify three visual opsin genes, rh1, sws1 and lws, in retinal mRNA of an ecologically and taxonomically diverse sample of snakes central to Walls' theory. We conclude that photoreceptors with superficially rod- or cone-like morphology are not limited to containing scotopic or photopic opsins, respectively. Walls' theory is essentially correct, and more research is needed to identify the patterns, processes and functional implications of transmutation. Future research will help to clarify the fundamental properties and physiology of photoreceptors adapted to function in different light levels. PMID:26817768

Dysfunction of outer segment guanylate cyclase caused by retinal disease related mutations

PubMed Central

Zägel, Patrick; Koch, Karl-Wilhelm

2014-01-01

Membrane bound guanylate cyclases are expressed in rod and cone cells of the vertebrate retina and mutations in several domains of rod outer segment guanylate cyclase 1 (ROS-GC1 encoded by the gene GUCY2D) correlate with different forms of retinal degenerations. In the present work we investigated the biochemical consequences of three point mutations, one is located in position P575L in the juxtamembrane domain close to the kinase homology domain and two are located in the cyclase catalytic domain at H1019P and P1069R. These mutations correlate with various retinal diseases like autosomal dominant progressive cone degeneration, e.g., Leber Congenital Amaurosis and a juvenile form of retinitis pigmentosa. Wildtype and mutant forms of ROS-GC1 were heterologously expressed in HEK cells, their cellular distribution was investigated and activity profiles in the presence and absence of guanylate cyclase-activating proteins were measured. The mutant P575L was active under all tested conditions, but it displayed a twofold shift in the Ca2+-sensitivity, whereas the mutant P1069R remained inactive despite normal expression levels. The mutation H1019P caused the cyclase to become more labile. The different biochemical consequences of these mutations seem to reflect the different clinical symptoms. The mutation P575L induces a dysregulation of the Ca2+-sensitive cyclase activation profile causing a slow progression of the disease by the distortion of the Ca2+-cGMP homeostasis. In contrast, a strong reduction in cGMP synthesis due to an inactive or structurally unstable ROS-GC1 would trigger more severe forms of retinal diseases. PMID:24616660

Interaction of Extracellular Domain 2 of the Human Retina-specific ATP-binding Cassette Transporter (ABCA4) with All-trans-retinal*

PubMed Central

Biswas-Fiss, Esther E.; Kurpad, Deepa S.; Joshi, Kinjalben; Biswas, Subhasis B.

2010-01-01

The retina-specific ATP-binding cassette (ABC) transporter, ABCA4, is essential for transport of all-trans-retinal from the rod outer segment discs in the retina and is associated with a broad range of inherited retinal diseases, including Stargardt disease, autosomal recessive cone rod dystrophy, and fundus flavimaculatus. A unique feature of the ABCA subfamily of ABC transporters is the presence of highly conserved, long extracellular loops or domains (ECDs) with unknown function. The high degree of sequence conservation and mapped disease-associated mutations in these domains suggests an important physiological significance. Conformational analysis using CD spectroscopy of purified, recombinant ECD2 protein demonstrated that it has an ordered and stable structure composed of 27 ± 3% α-helix, 20 ± 3% β-pleated sheet, and 53 ± 3% coil. Significant conformational changes were observed in disease-associated mutant proteins. Using intrinsic tryptophan fluorescence emission spectrum of ECD2 polypeptide and fluorescence anisotropy, we have demonstrated that this domain specifically interacts with all-trans-retinal. Furthermore, the retinal interaction appeared preferential for the all-trans-isomer and was directly measurable through fluorescence anisotropy analysis. Our results demonstrate that the three macular degeneration-associated mutations lead to significant changes in the secondary structure of the ECD2 domain of ABCA4, as well as in its interaction with all-trans-retinal. PMID:20404325

Woodland salamander and small mammal responses to alternative silvicultural practices in the Southern Appalachians of North Carolina

Treesearch

W. Mark Ford; Michael A. Menzel; Timothy S. McCay; Jonathan W. Gassett; Joshua Laerm

2000-01-01

The effects of 2 years post-treatment of group selection and 2-aged timber harvests on woodland salamanders and mammals were assessed on stands in high elevation, southern Appalachian northern red oak (Quercus rubra)-flame azalea (Rhododendron calendulaceum) communities, in the Nantahala National Forest. We collected 4 salamander...

Argus II retinal prosthesis system: a review of patient selection criteria, surgical considerations, and post-operative outcomes.

PubMed

Finn, Avni P; Grewal, Dilraj S; Vajzovic, Lejla

2018-01-01

Retinitis pigmentosa (RP) is a group of heterogeneous inherited retinal degenerative disorders characterized by progressive rod and cone dysfunction and ensuing photoreceptor loss. Many patients suffer from legal blindness by their 40s or 50s. Artificial vision is considered once patients have lost all vision to the point of bare light perception or no light perception. The Argus II retinal prosthesis system is one such artificial vision device approved for patients with RP. This review focuses on the factors important for patient selection. Careful pre-operative screening, counseling, and management of patient expectations are critical for the successful implantation and visual rehabilitation of patients with the Argus II device.

High-speed adaptive optics line scan confocal retinal imaging for human eye

PubMed Central

Wang, Xiaolin; Zhang, Yuhua

2017-01-01

Purpose Continuous and rapid eye movement causes significant intraframe distortion in adaptive optics high resolution retinal imaging. To minimize this artifact, we developed a high speed adaptive optics line scan confocal retinal imaging system. Methods A high speed line camera was employed to acquire retinal image and custom adaptive optics was developed to compensate the wave aberration of the human eye’s optics. The spatial resolution and signal to noise ratio were assessed in model eye and in living human eye. The improvement of imaging fidelity was estimated by reduction of intra-frame distortion of retinal images acquired in the living human eyes with frame rates at 30 frames/second (FPS), 100 FPS, and 200 FPS. Results The device produced retinal image with cellular level resolution at 200 FPS with a digitization of 512×512 pixels/frame in the living human eye. Cone photoreceptors in the central fovea and rod photoreceptors near the fovea were resolved in three human subjects in normal chorioretinal health. Compared with retinal images acquired at 30 FPS, the intra-frame distortion in images taken at 200 FPS was reduced by 50.9% to 79.7%. Conclusions We demonstrated the feasibility of acquiring high resolution retinal images in the living human eye at a speed that minimizes retinal motion artifact. This device may facilitate research involving subjects with nystagmus or unsteady fixation due to central vision loss. PMID:28257458

Early Miocene origin and cryptic diversification of South American salamanders

PubMed Central

2013-01-01

Background The currently recognized species richness of South American salamanders is surprisingly low compared to North and Central America. In part, this low richness may be due to the salamanders being a recent arrival to South America. Additionally, the number of South American salamander species may be underestimated because of cryptic diversity. The aims of our present study were to infer evolutionary relationships, lineage diversity, and timing of divergence of the South American Bolitoglossa using mitochondrial and nuclear sequence data from specimens primarily from localities in the Andes and upper Amazon Basin. We also estimated time of colonization of South America to test whether it is consistent with arrival via the Panamanian Isthmus, or land bridge connection, at its traditionally assumed age of 3 million years. Results Divergence time estimates suggest that Bolitoglossa arrived in South America from Central America by at least the Early Miocene, ca. 23.6 MYA (95% HPD 15.9-30.3 MYA), and subsequently diversified. South American salamanders of the genus Bolitoglossa show strong phylogeographic structure at fine geographic scales and deep divergences at the mitochondrial gene cytochrome b (Cytb) and high diversity at the nuclear recombination activating gene-1 (Rag1). Species often contain multiple genetically divergent lineages that are occasionally geographically overlapping. Single specimens from two southeastern localities in Ecuador are sister to the equatoriana-peruviana clade and genetically distinct from all other species investigated to date. Another single exemplar from the Andes of northwestern Ecuador is highly divergent from all other specimens and is sister to all newly studied samples. Nevertheless, all sampled species of South American Bolitoglossa are members of a single clade that is one of several constituting the subgenus Eladinea, one of seven subgenera in this large genus. Conclusions The ancestors of South American salamanders

Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function.

PubMed

Nishiguchi, Koji M; Friedman, James S; Sandberg, Michael A; Swaroop, Anand; Berson, Eliot L; Dryja, Thaddeus P

2004-12-21

Mice lacking the transcription factor Nrl have no rod photoreceptors and an increased number of short-wavelength-sensitive cones. Missense mutations in NRL are associated with autosomal dominant retinitis pigmentosa; however, the phenotype associated with the loss of NRL function in humans has not been reported. We identified two siblings who carried two allelic mutations: a predicted null allele (L75fs) and a missense mutation (L160P) altering a highly conserved residue in the domain involved in DNA-binding-site recognition. In vitro luciferase reporter assays demonstrated that the NRL-L160P mutant had severely reduced transcriptional activity compared with the WT NRL protein, consistent with a severe loss of function. The affected patients had night blindness since early childhood, consistent with a severe reduction in rod function. Color vision was normal, suggesting the presence of all cone color types; nevertheless, a comparison of central visual fields evaluated with white-on-white and blue-on-yellow light stimuli was consistent with a relatively enhanced function of short-wavelength-sensitive cones in the macula. The fundi had signs of retinal degeneration (such as vascular attenuation) and clusters of large, clumped, pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium (clumped pigmentary retinal degeneration). Our report presents an unusual clinical phenotype in humans with loss-of-function mutations in NRL.

Strategies for modeling habitat relationships of uncommon species: An example using the Siskiyou Mountains salamander (Plethodon stormi).

Treesearch

Hartwell H. Welsh; Howard Stauffer; David R. Clayton; Lisa M. Ollivier

2007-01-01

We analyzed environmental relationships of the Siskiyou Mountains salamander, comparing attributes at the landscape, macro- and micro-environmental scales, and the three scales combined, to determine which attributes best predicted salamander presence. Separate analyses were conducted for sites on the north and south sides of the Siskiyou Mountains which basically...

Ontogenic retinal changes in three ecologically distinct elopomorph fishes (Elopomorpha:Teleostei) correlate with light environment and behavior.

PubMed

Taylor, Scott M; Loew, Ellis R; Grace, Michael S

2015-01-01

Unlike the mammalian retina, the teleost fish retina undergoes persistent neurogenesis from intrinsic stem cells. In marine teleosts, most cone photoreceptor genesis occurs early in the embryonic and larval stages, and rods are added primarily during and after metamorphosis. This study demonstrates a developmental paradigm in elopomorph fishes in which retinas are rod-dominated in larvae, but undergo periods of later cone genesis. Retinal characteristics were compared at different developmental stages among three ecologically distinct elopomorph fishes-ladyfish (Elops saurus), bonefish (Albula vulpes), and speckled worm eel (Myrophis punctatus). The objectives were to improve our understanding of (1) the developmental strategy in the elopomorph retina, (2) the functional architecture of the retina as it relates to ecology, and (3) how the light environment influences photoreceptor genesis. Photoreceptor morphologies, distributions, and spectral absorption were studied at larval, juvenile, and adult stages. Premetamorphic retinas in all three species are rod-dominated, but the retinas of these species undergo dramatic change over the course of development, resulting in juvenile and adult retinal characteristics that correlate closely with ecology. Adult E. saurus has high rod densities, grouped photoreceptors, a reflective tapetum, and longer-wavelength photopigments, supporting vision in turbid, low-light conditions. Adult A. vulpes has high cone densities, low rod densities, and shorter-wavelength photopigments, supporting diurnal vision in shallow, clear water. M. punctatus loses cones during metamorphosis, develops new cones after settlement, and maintains high rod but low cone densities, supporting primarily nocturnal vision. M. punctatus secondary cone genesis occurs rapidly throughout the retina, suggesting a novel mechanism of vertebrate photoreceptor genesis. Finally, in postsettlement M. punctatus, the continuous presence or absence of visible light

Homozygosity Mapping in Patients with Cone–Rod Dystrophy: Novel Mutations and Clinical Characterizations

PubMed Central

Littink, Karin W.; Koenekoop, Robert K.; van den Born, L. Ingeborgh; Collin, Rob W. J.; Moruz, Luminita; Veltman, Joris A.; Roosing, Susanne; Zonneveld, Marijke N.; Omar, Amer; Darvish, Mahshad; Lopez, Irma; Kroes, Hester Y.; van Genderen, Maria M.; Hoyng, Carel B.; Rohrschneider, Klaus; van Schooneveld, Mary J.; Cremers, Frans P. M.

2010-01-01

Purpose. To determine the genetic defect and to describe the clinical characteristics in a cohort of mainly nonconsanguineous cone–rod dystrophy (CRD) patients. Methods. One hundred thirty-nine patients with diagnosed CRD were recruited. Ninety of them were screened for known mutations in ABCA4, and those carrying one or two mutations were excluded from further research. Genome-wide homozygosity mapping was performed in the remaining 108. Known genes associated with autosomal recessive retinal dystrophies located within a homozygous region were screened for mutations. Patients in whom a mutation was detected underwent further ophthalmic examination. Results. Homozygous sequence variants were identified in eight CRD families, six of which were nonconsanguineous. The variants were detected in the following six genes: ABCA4, CABP4, CERKL, EYS, KCNV2, and PROM1. Patients carrying mutations in ABCA4, CERKL, and PROM1 had typical CRD symptoms, but a variety of retinal appearances on funduscopy, optical coherence tomography, and autofluorescence imaging. Conclusions. Homozygosity mapping led to the identification of new mutations in consanguineous and nonconsanguineous patients with retinal dystrophy. Detailed clinical characterization revealed a variety of retinal appearances, ranging from nearly normal to extensive retinal remodeling, retinal thinning, and debris accumulation. Although CRD was initially diagnosed in all patients, the molecular findings led to a reappraisal of the diagnosis in patients carrying mutations in EYS, CABP4, and KCNV2. PMID:20554613

Retinal Degeneration in a Rodent Model of Smith-Lemli-Opitz Syndrome

PubMed Central

Fliesler, Steven J.; Peachey, Neal S.; Richards, Michael J.; Nagel, Barbara A.; Vaughan, Dana K.

2010-01-01

Objective To assess the electrophysiologic, histologic, and biochemical features of an animal model of Smith-Lemli-Opitz syndrome (SLOS). Methods Sprague-Dawley rats were treated with AY9944, a selective inhibitor of 3β-hydroxysterol-Δ7-reductase (the affected enzyme in SLOS). Dark- and light-adapted electroretinograms were obtained from treated and control animals. From each animal, 1 retina was analyzed by microscopy, and the contralateral retina plus serum samples were analyzed for sterol composition. The main outcome measures were rod and cone electroretinographic amplitudes and implicit times, outer nuclear layer (ONL) thickness, rod outer segment length, pyknotic ONL nucleus counts, and the 7-dehydrocholesterol/ cholesterol mole ratio in the retina and serum. Results By 10 weeks’ postnatal age, rod and cone electroretinographic wave amplitudes in AY9944-treated animals were significantly reduced and implicit times were significantly increased relative to controls. Maximal rod photoresponse and gain values were reduced approximately 2-fold in treated animals relative to controls. The ONL thickness and average rod outer segment length were reduced by approximately 18% and 33%, respectively, and ONL pyknotic nucleus counts were approximately 4.5-fold greater in treated animals relative to controls. The retinal pigment epithelium of treated animals contained massive amounts of membranous/lipid inclusions not routinely observed in controls. The 7-dehydrocholesterol/cholesterol mole ratios in treated retinas and serum samples were approximately 5:1 and 9:1, respectively, whereas the ratios in control tissues were essentially zero. Conclusions This rodent model exhibits the key biochemical hallmarks associated with SLOS and displays electrophysiologic deficits comparable to or greater than those observed in the human disease. Clinical Relevance These results predict retinal degeneration in patients with SLOS, particularly those with the more severe (type II

Reproductive biology of the Del Norte salamander (Plethodon elongatus).

Treesearch

Clara A. Wheeler; Hartwell H. Welsh Jr.; Lisa M. Ollivier

2013-01-01

We examined seasonal reproductive patterns of the Del Norte Salamander, Plethodon elongatus, in mixed conifer and hardwood forests of northwestern California and southwestern Oregon. Seasonal size differences in reproductive structures suggested that maximum spermatogenic activity occurred during the late summer, with spermatozoa transfer to the...

Overview of the status of the Cheat Mountain salamander

Treesearch

Thomas K. Pauley

2010-01-01

Plethodon nettingi, the Cheat Mountain salamander, is endemic to the high elevations of the Allegheny Mountains in eastern West Virginia. In 1938, N.B. Green named the species from specimens collected at Barton Knob, Randolph County, in honor of his friend and colleague Graham Netting.

Rapid diversification and dispersal during periods of global warming by plethodontid salamanders

PubMed Central

Vieites, David R.; Min, Mi-Sook; Wake, David B.

2007-01-01

A phylogeny and timescale derived from analyses of multilocus nuclear DNA sequences for Holarctic genera of plethodontid salamanders reveal them to be an old radiation whose common ancestor diverged from sister taxa in the late Jurassic and underwent rapid diversification during the late Cretaceous. A North American origin of plethodontids was followed by a continental-wide diversification, not necessarily centered only in the Appalachian region. The colonization of Eurasia by plethodontids most likely occurred once, by dispersal during the late Cretaceous. Subsequent diversification in Asia led to the origin of Hydromantes and Karsenia, with the former then dispersing both to Europe and back to North America. Salamanders underwent rapid episodes of diversification and dispersal that coincided with major global warming events during the late Cretaceous and again during the Paleocene–Eocene thermal optimum. The major clades of plethodontids were established during these episodes, contemporaneously with similar phenomena in angiosperms, arthropods, birds, and mammals. Periods of global warming may have promoted diversification and both inter- and transcontinental dispersal in northern hemisphere salamanders by making available terrain that shortened dispersal routes and offered new opportunities for adaptive and vicariant evolution. PMID:18077422

Phylogeography of Sardinian cave salamanders (genus Hydromantes) is mainly determined by geomorphology.

PubMed

Chiari, Ylenia; van der Meijden, Arie; Mucedda, Mauro; Lourenço, João M; Hochkirch, Axel; Veith, Michael

2012-01-01

Detecting the factors that determine the interruption of gene flow between populations is key to understanding how speciation occurs. In this context, caves are an excellent system for studying processes of colonization, differentiation and speciation, since they represent discrete geographical units often with known geological histories. Here, we asked whether discontinuous calcareous areas and cave systems represent major barriers to gene flow within and among the five species of Sardinian cave salamanders (genus Hydromantes) and whether intraspecific genetic structure parallels geographic distance within and among caves. We generated mitochondrial cytochrome b gene sequences from 184 individuals representing 48 populations, and used a Bayesian phylogeographic approach to infer possible areas of cladogenesis for these species and reconstruct historical and current dispersal routes among distinct populations. Our results show deep genetic divergence within and among all Sardinian cave salamander species, which can mostly be attributed to the effects of mountains and discontinuities in major calcareous areas and cave systems acting as barriers to gene flow. While these salamander species can also occur outside caves, our results indicate that there is a very poor dispersal of these species between separate cave systems.

The dynamic evolutionary history of genome size in North American woodland salamanders.

PubMed

Newman, Catherine E; Gregory, T Ryan; Austin, Christopher C

2017-04-01

The genus Plethodon is the most species-rich salamander genus in North America, and nearly half of its species face an uncertain future. It is also one of the most diverse families in terms of genome sizes, which range from 1C = 18.2 to 69.3 pg, or 5-20 times larger than the human genome. Large genome size in salamanders results in part from accumulation of transposable elements and is associated with various developmental and physiological traits. However, genome sizes have been reported for only 25% of the species of Plethodon (14 of 55). We collected genome size data for Plethodon serratus to supplement an ongoing phylogeographic study, reconstructed the evolutionary history of genome size in Plethodontidae, and inferred probable genome sizes for the 41 species missing empirical data. Results revealed multiple genome size changes in Plethodon: genomes of western Plethodon increased, whereas genomes of eastern Plethodon decreased, followed by additional decreases or subsequent increases. The estimated genome size of P. serratus was 21 pg. New understanding of variation in genome size evolution, along with genome size inferences for previously unstudied taxa, provide a foundation for future studies on the biology of plethodontid salamanders.

Mercury Speciation and Trophic Magnification Slopes in Giant Salamander Larvae from the Pacific Northwest, USA

NASA Astrophysics Data System (ADS)

Bank, M. S.; Crocker, J.; Wachtl, J.; Kleeman, P.; Fellers, G.; Currens, C.; Hothem, R.; Madej, M. A.

2014-12-01

Mercury (Hg) contamination of stream salamanders in the Pacific Northwest region of the United States has received little attention. Here we report total Hg (HgT) and methyl mercury (MeHg) concentrations in larval giant salamanders (Dicamptodon spp.) and surface water from forested and chaparral lotic ecosystems distributed along a latitudinal gradient throughout Northern California and Washington. To test hypotheses related to potential effects from mining land-use activities, salamander larvae were also sampled from a reference site at Whiskeytown National Recreation Area, California, and at a nearby, upstream site (Shasta county) on Bureau of Land Management land where Hg contamination from gold mining activities has been documented. HgT concentrations in whole body larvae ranged from 4.6 to 74.5 ng/g wet wt. and percent MeHg ranged from 67% to 86%. Both HgT and MeHg larval tissue concentrations were significantly higher at the mining site in comparison to measured background levels (P < 0.001). We conclude that salamander larvae in remote stream ecosystems, where Hg sources were dominated by atmospheric deposition, were generally low in HgT and MeHg and, in comparison, watersheds with a legacy of land-use practices (i.e., mining operations) had approximately 4.5 - 5.5 times the level of HgT bioaccumulation. Moreover, trophic magnification slopes were highest in the Shasta county region where mining was present. These findings suggest that mining activities increase HgT and MeHg exposure to salamander larvae in the region and may present a threat to other higher trophically positioned organisms, and their associated food webs.

Platelet-Derived Growth Factor-BB Lessens Light-Induced Rod Photoreceptor Damage in Mice.

PubMed

Takahashi, Kei; Shimazawa, Masamitsu; Izawa, Hiroshi; Inoue, Yuki; Kuse, Yoshiki; Hara, Hideaki

2017-12-01

Platelet-derived growth factor (PDGF)-BB is known to have neuroprotective effects against various neurodegenerative disorders. The purpose of this study was to determine whether PDGF-BB can be neuroprotective against light-induced photoreceptor damage in mice. Mice were exposed to 8000-lux luminance for 3 hours to induce phototoxicity. Two hours before light exposure, the experimental mice were injected with PDGF-BB intravitreally, and the control mice were injected with phosphate-buffered saline. The light-exposed PDGF-BB-injected mice and saline-injected mice were evaluated electroretinographically and histologically. The site and expression levels of PDGFR-β and PDGF-BB were determined by immunostaining and Western blotting, respectively. The effect of PDGF-BB on light-induced cone and rod photoreceptor damage was also evaluated in vitro in 661W cells, a murine cone photoreceptor cell line, and in primary retinal cell cultures. An intravitreal injection of PDGF-BB significantly reduced the decrease in the amplitudes of the electroretinograms (ERGs) and the thinning of the outer nuclear layer (ONL) induced by the light exposure. It also reduced the number of TUNEL-positive cells in the ONL. PDGFR-β was expressed in the rod outer segments (OSs) but not the cone OSs. The levels of PDGF-BB and PDGFR-β were decreased after light irradiation. In addition, PDGF-BB had protective effects against light-induced damage to cells of rod photoreceptors but had no effect on the 661W cells in vitro. These findings indicate that PDGF-BB reduces the degree of light-induced retinal damage by activating PDGFR-β in rod photoreceptors. These findings suggest that PDGF-BB could play a role in the prevention of degeneration in eyes susceptible to phototoxicity.

Biogeography and body size shuffling of aquatic salamander communities on a shifting refuge

PubMed Central

Bonett, Ronald M.; Trujano-Alvarez, Ana Lilia; Williams, Michael J.; Timpe, Elizabeth K.

2013-01-01

Freshwater habitats of coastal plains are refugia for many divergent vertebrate lineages, yet these environments are highly vulnerable to sea-level fluctuations, which suggest that resident communities have endured dynamic histories. Using the fossil record and a multi-locus nuclear phylogeny, we examine divergence times, biogeography, body size evolution and patterns of community assembly of aquatic salamanders from North American coastal plains since the Late Cretaceous. At least five salamander families occurred on the extensive Western Interior Coastal Plain (WICP), which existed from the Late Cretaceous through the Eocene. Four of these families subsequently colonized the emergent Southeastern Coastal Plain (SECP) by the Early Oligocene to Late Miocene. Three families ultimately survived and underwent extensive body size evolution in situ on the SECP. This included at least two major size reversals in recent taxa that are convergent with confamilial WICP ancestors. Dynamics of the coastal plain, major lineage extinctions and frequent extreme changes in body size have resulted in significant shuffling of the size structure of aquatic salamander communities on this shifting refuge since the Cretaceous. PMID:23466988

In vivo super-resolution imaging of transient retinal phototropism evoked by oblique light stimulation.

PubMed

Lu, Yiming; Liu, Changgeng; Yao, Xincheng

2018-05-01

Rod-dominated transient retinal phototropism (TRP) has been observed in freshly isolated retinas, promising a noninvasive biomarker for objective assessment of retinal physiology. However, in vivo mapping of TRP is challenging due to its subcellular signal magnitude and fast time course. We report here a virtually structured detection-based super-resolution ophthalmoscope to achieve subcellular spatial resolution and millisecond temporal resolution for in vivo imaging of TRP. Spatiotemporal properties of in vivo TRP were characterized corresponding to variable light intensity stimuli, confirming that TRP is tightly correlated with early stages of phototransduction. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Interphotoreceptor matrix components in retinal cell transplants.

PubMed

Juliusson, B; Mieziewska, K; Bergström, A; Wilke, K; Van Veen, T; Ehinger, B

1994-05-01

To further investigate the functional potential of retinal transplants we have used immunocytochemistry to study the distribution of four different interphotoreceptor matrix (IPM)-specific components in rabbit retinal transplants. The different components were: interphotoreceptor retinoid-binding protein (IRBP), chondroitin-6-sulfate, F22 antigen and peanut agglutinin (PNA) binding structures. IRBP acts as a retinoid-transport protein between the neural retina and the retinal pigment epithelium. Chondroitin-6-sulfate is a glycosaminoglycan and a part of the insoluble IPM skeleton. The identity and role of the F22 antigen is not known. However, it is a 250 kDa protein localized to specific extracellular compartments such as teh IPM. PNA is a lectin with a high binding affinity for D-galactose-beta (1-3) N-acetyl-D-galactosamine disaccharide linkages and binds to IPM domains surrounding cones, but not rods. The transplants (15-day-old embryonic rabbit retina) were placed between the neural retina and retinal pigment epithelium in adult hosts. The transplants developed the typical rosette formations with photoreceptors toward the center. IRBP labeling was distinct in the IPM in the host retina. However, no IRBP labeling could be detected in the transplants. The chondroitin-6-sulfate and F22 antibodies strongly labeled the IPM in the host retina and corresponding structures in the center of rosettes. A cone-specific labeling with PNA could be seen in the host retina. In the transplants, however, PNA labeling appeared in association with many more photoreceptors than in the host retina. There is no previous study available on the IPM in retinal cell transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

Rod Electroretinograms Elicited by Silent Substitution Stimuli from the Light-Adapted Human Eye

PubMed Central

Maguire, John; Parry, Neil R. A.; Kremers, Jan; Kommanapalli, Deepika; Murray, Ian J.; McKeefry, Declan J.

2016-01-01

Purpose To demonstrate that silent substitution stimuli can be used to generate electroretinograms (ERGs) that effectively isolate rod photoreceptor function in humans without the need for dark adaptation, and that this approach constitutes a viable alternative to current clinical standard testing protocols. Methods Rod-isolating and non-isolating sinusoidal flicker stimuli were generated on a 4 primary light-emitting diode (LED) Ganzfeld stimulator to elicit ERGs from participants with normal and compromised rod function who had not undergone dark-adaptation. Responses were subjected to Fourier analysis, and the amplitude and phase of the fundamental were used to examine temporal frequency and retinal illuminance response characteristics. Results Electroretinograms elicited by rod-isolating silent substitution stimuli exhibit low-pass temporal frequency response characteristics with an upper response limit of 30 Hz. Responses are optimal between 5 and 8 Hz and between 10 and 100 photopic trolands (Td). There is a significant correlation between the response amplitudes obtained with the silent substitution method and current standard clinical protocols. Analysis of signal-to-noise ratios reveals significant differences between subjects with normal and compromised rod function. Conclusions Silent substitution provides an effective method for the isolation of human rod photoreceptor function in subjects with normal as well as compromised rod function when stimuli are used within appropriate parameter ranges. Translational Relevance This method of generating rod-mediated ERGs can be achieved without time-consuming periods of dark adaptation, provides improved isolation of rod- from cone-based activity, and will lead to the development of faster clinical electrophysiologic testing protocols with improved selectivity. PMID:27617180

Multimodal communication, mismatched messages and the effects of turbidity on the antipredator behavior of the Barton Springs salamander, Eurycea sosorum.

PubMed

Zabierek, Kristina C; Gabor, Caitlin R

2016-09-01

Prey may use multiple sensory channels to detect predators, whose cues may differ in altered sensory environments, such as turbid conditions. Depending on the environment, prey may use cues in an additive/complementary manner or in a compensatory manner. First, to determine whether the purely aquatic Barton Springs salamander, Eurycea sosorum, show an antipredator response to visual cues, we examined their activity when exposed to either visual cues of a predatory fish (Lepomis cyanellus) or a non-predatory fish (Etheostoma lepidum). Salamanders decreased activity in response to predator visual cues only. Then, we examined the antipredator response of these salamanders to all matched and mismatched combinations of chemical and visual cues of the same predatory and non-predatory fish in clear and low turbidity conditions. Salamanders decreased activity in response to predator chemical cues matched with predator visual cues or mismatched with non-predator visual cues. Salamanders also increased latency to first move to predator chemical cues mismatched with non-predator visual cues. Salamanders decreased activity and increased latency to first move more in clear as opposed to turbid conditions in all treatment combinations. Our results indicate that salamanders under all conditions and treatments preferentially rely on chemical cues to determine antipredator behavior, although visual cues are potentially utilized in conjunction for latency to first move. Our results also have potential conservation implications, as decreased antipredator behavior was seen in turbid conditions. These results reveal complexity of antipredator behavior in response to multiple cues under different environmental conditions, which is especially important when considering endangered species. Copyright © 2016 Elsevier B.V. All rights reserved.

Reproductive allometry in three species of Dusky Salamanders

Treesearch

Richard C. Bruce

2014-01-01

Desmognathus comprises 21 currently recognized species of salamanders in eastern North America. Assemblages of 3–6 species occur in the Appalachian Mountains, wherein the larger species are more aquatic and the smaller more terrestrial. Adaptive divergence along the habitat gradient from stream to forest involves variation in such life-history traits as age and size at...

Acid precipitation and reproductive success of Ambystoma salamanders

Treesearch

F. Harvey Pough; Richard E. Wilson

1976-01-01

The two species of mole salamander that occur in the Ithaca, New York, region (Ambystoma maculatum and A. jeffersonianum) breed in temporary ponds that are formed by accumulation of melted snow and spring rains. Water in many of these pools during the breeding season is acid; pH values as low as 3.5 have been measured. In...

3D Imaging of Retinal Pigment Epithelial Cells in the Living Human Retina

PubMed Central

Liu, Zhuolin; Kocaoglu, Omer P.; Miller, Donald T.

2016-01-01

Purpose Dysfunction of the retinal pigment epithelium (RPE) underlies numerous retinal pathologies, but biomarkers sensitive to RPE change at the cellular level are limited. In this study, we used adaptive optics optical coherence tomography (AO-OCT) in conjunction with organelle motility as a novel contrast mechanism to visualize RPE cells and characterize their 3-dimensional (3D) reflectance profile. Methods Using the Indiana AO-OCT imaging system (λc = 790 nm), volumes were acquired in the macula of six normal subjects (25–61 years). Volumes were registered in 3D with subcellular accuracy, layers segmented, and RPE and photoreceptor en face images extracted and averaged. Voronoi and two-dimensional (2D) power spectra analyses were applied to the images to quantify RPE and cone packing and cone-to-RPE ratio. Results Adaptive optics OCT revealed two distinct reflectance patterns at the depth of the RPE. One is characterized by the RPE interface with rod photoreceptor tips, the second by the RPE cell nuclei and surrounding organelles, likely melanin. Increasing cell contrast by averaging proved critical for observing the RPE cell mosaic, successful in all subjects and retinal eccentricities imaged. Retinal pigment epithelium mosaic packing and cell thickness generally agreed with that of histology and in vivo studies using other imaging modalities. Conclusions We have presented, to our knowledge, the first detailed characterization of the 3D reflectance profile of individual RPE cells and their relation to cones and rods in the living human retina. Success in younger and older eyes establishes a path for testing aging effects in larger populations. Because the technology is based on OCT, our measurements will aid in interpreting clinical OCT images. PMID:27472277

Impacts of a gape limited Brook Trout, Salvelinus fontinalis, on larval Northwestern salamander, Ambystoma gracile, growth: A field enclosure experiment

USGS Publications Warehouse

Currens, C.R.; Liss, W.J.; Hoffman, R.L.

2007-01-01

The formation of amphibian population structure is directly affected by predation. Although aquatic predators have been shown to have direct negative effects on larval salamanders in laboratory and field experiments, the potential impacts of gape-limited fish on larval salamander growth has been largely underexplored. We designed an enclosure experiment conducted in situ to quantify the effects of gape-limited Brook Trout (Salvelinus fontinalis) on larval Northwestern Salamander (Ambystoma gracile) growth. We specifically tested whether the presence of fish too small to consume larvae had a negative effect on larval growth. The results of this study indicate that the presence of a gape-limited S. fontinalis can have a negative effect on growth of larval A. gracile salamanders. Copyright 2007 Society for the Study of Amphibians and Reptiles.

Understanding the Function of Genes Involved in Inherited Retinal Degeneration-Insights into the Pathogenesis and Function of C8ORF37

NASA Astrophysics Data System (ADS)

Sharif, Ali Sakawa

Inherited retinal degenerative diseases (IRD) are a group of disorders that lead to progressive deterioration of mainly the photoreceptors. Retinitis pigmentosa (RP) and cone-rod dystrophy (CRD) are two forms of IRDs. RP is the most common form of IRD and is due to rod photoreceptor degeneration followed by cone photoreceptor loss. CRD, on the other hand, is characterized by the loss of cones or the concurrent degeneration of both cones and rods. Both RP and CRD are presently incurable. More than 200 genes have been identified to cause IRDs and the functions of many of these genes remain unclear. Mutations in a novel gene, C8ORF37, were identified to cause recessive, severe, and early-onset RP and CRD. I, therefore, pioneered in characterizing the role of C8ORF37 in the retina. This dissertation is comprised of four chapters that is organized as follows: (1) summary of an ocular disorder (2) a genetic model of a retinal disorder (3) biochemical/proteomic analysis of C8ORF37 (4) potential clinical applications. A summary of ocular disorders is discussed in Chapter 1, with an emphasis on CRD. Chapter 2 focuses on the generation and characterization of C8orf37 mutant mouse models that recapitulate the retinal pathologies observed in human patients. In C8orf37 knockout retinas, the outer segment (OS) was nonuniform, swollen, and wider in width when compared to the controls. Moreover, many OS membrane proteins were reduced in the retina of C8orf37 knockout, including CNGB1 and RDS, proteins essential for OS disc morphogenesis and alignment. Our findings shed new light on the pathogenesis underlying retinal dysfunction and degeneration in C8ORF37-deficient patients. To determine the function of a novel protein, a powerful approach is by identifying its binding partners. In Chapter 3, I discuss GST pull-down using bovine retinal lysates, yeast-two-hybrid, and immunoprecipitation with mouse retinal lysate in order to identify C8ORF37-interacting proteins. Our pull

Spatial and seasonal variation in the ecological significance of nutrient recycling by larval salamanders in Appalachian headwater streams

Treesearch

S. Conor Keitzer; Reuben R. Goforth

2013-01-01

Salamanders are abundant consumers in many temperate streams and may be important recyclers of biologically essential nutrients, but their ecological role is poorly understood. The ecological significance of nutrient recycling by salamanders may vary spatially and seasonally because of their potentially patchy distribution in streams and the dynamic nature of stream...

NMNAT1 variants cause cone and cone-rod dystrophy.

PubMed

Nash, Benjamin M; Symes, Richard; Goel, Himanshu; Dinger, Marcel E; Bennetts, Bruce; Grigg, John R; Jamieson, Robyn V

2018-03-01

Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.

Life-history perspective of adaptive radiation in desmognathine salamanders

Treesearch

Richard C. Bruce

1996-01-01

This study investigates interspecific variation in age at first reproduction, fecundity, and body size in multispecies assemblages of desmognathine salamanders. The hypotheses tested are that interspecific differences in body size among desmognathines stem proximately from variation in age at first reproduction and that variation in the latter trait is positively...

Vesicle Pool Size at the Salamander Cone Ribbon Synapse

PubMed Central

Bartoletti, Theodore M.; Babai, Norbert

2010-01-01

Cone light responses are transmitted to postsynaptic neurons by changes in the rate of synaptic vesicle release. Vesicle pool size at the cone synapse constrains the amount of release and can thus shape contrast detection. We measured the number of vesicles in the rapidly releasable and reserve pools at cone ribbon synapses by performing simultaneous whole cell recording from cones and horizontal or off bipolar cells in the salamander retinal slice preparation. We found that properties of spontaneously occurring miniature excitatory postsynaptic currents (mEPSCs) are representative of mEPSCs evoked by depolarizing presynaptic stimulation. Strong, brief depolarization of the cone stimulated release of the entire rapidly releasable pool (RRP) of vesicles. Comparing charge transfer of the EPSC with mEPSC charge transfer, we determined that the fast component of the EPSC reflects release of ∼40 vesicles. Comparing EPSCs with simultaneous presynaptic capacitance measurements, we found that horizontal cell EPSCs constitute 14% of the total number of vesicles released from a cone terminal. Using a fluorescent ribeye-binding peptide, we counted ∼13 ribbons per cone. Together, these results suggest each cone contacts a single horizontal cell at ∼2 ribbons. The size of discrete components in the EPSC amplitude histogram also suggested ∼2 ribbon contacts per cell pair. We therefore conclude there are ∼20 vesicles per ribbon in the RRP, similar to the number of vesicles contacting the plasma membrane at the ribbon base. EPSCs evoked by lengthy depolarization suggest a reserve pool of ∼90 vesicles per ribbon, similar to the number of additional docking sites further up the ribbon. PMID:19923246

Mutation K42E in dehydrodolichol diphosphate synthase (DHDDS) causes recessive retinitis pigmentosa.

PubMed

Lam, Byron L; Züchner, Stephan L; Dallman, Julia; Wen, Rong; Alfonso, Eduardo C; Vance, Jeffery M; Peričak-Vance, Margaret A

2014-01-01

A single-nucleotide mutation in the gene that encodes DHDDS has been identified by whole exome sequencing as the cause of the non-syndromic recessive retinitis pigmentosa (RP) in a family of Ashkenazi Jewish origin in which three of the four siblings have early onset retinal degeneration. The peripheral retinal degeneration in the affected siblings was evident in the initial examination in 1992 and only one had detectable electroretinogram (ERG) that suggested cone-rod dysfunction. The pigmentary retinal degeneration subsequently progressed rapidly. The identified mutation changes the highly conserved residue Lys42 to Glu, resulting in lower catalytic efficiency. Patterns of plasma transferrin isoelectric focusing gel were normal in all family members, indicating no significant abnormality in protein glycosylation. Dolichols have been shown to influence the fluidity and of the membrane and promote vesicle fusion. Considering that photoreceptor outer segments contain stacks of membrane discs, we believe that the mutation may lead to low dolichol levels in photoreceptor outer segments, resulting in unstable membrane structure that leads to photoreceptor degeneration.

Four-Year Placebo-Controlled Trial of Docosahexaenoic Acid in X-Linked Retinitis Pigmentosa (DHAX Trial)

PubMed Central

Hoffman, Dennis R.; Hughbanks-Wheaton, Dianna K.; Pearson, N. Shirlene; Fish, Gary E.; Spencer, Rand; Takacs, Alison; Klein, Martin; Locke, Kirsten G.; Birch, David G.

2016-01-01

IMPORTANCE X-linked retinitis pigmentosa is a severe inherited retinal degenerative disease with a frequency of 1 in 100 000 persons. Because no cure is available for this orphan disease and treatment options are limited, slowing of disease progression would be a meaningful outcome. OBJECTIVE To determine whether high-dose docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, slows progression of X-linked retinitis pigmentosa measured by cone electroretinography (ERG). DESIGN, SETTING, AND PARTICIPANTS A 4-year, single-site, randomized, placebo-controlled, double-masked phase 2 clinical trial at a research center specializing in medical retina. Seventy-eight male patients diagnosed as having X-linked retinitis pigmentosa were randomized to DHA or placebo. Data were omitted for 2 patients with non–X-linked retinitis pigmentosa and 16 patients who were unable to follow protocol during the first year. The remaining participants were tested annually and composed a modified intent-to-treat cohort (DHA group, n = 33; placebo group, n = 27). INTERVENTIONS All participants received a multivitamin and were randomly assigned to oral DHA (30 mg/kg/d) or placebo. MAIN OUTCOMES AND MEASURES The primary outcome was the rate of loss of cone ERG function. Secondary outcomes were rod and maximal ERG amplitudes and cone ERG implicit times. Capsule counts and red blood cell DHA levels were assessed to monitor adherence. RESULTS Average (6-month to 4-year) red blood cell DHA levels were 4-fold higher in the DHA group than in the placebo group (P < .001). There was no difference between the DHA and placebo groups in the rate of cone ERG functional loss (0.028 vs 0.022 log µV/y, respectively; P = .30). No group differences were evident for change in rod ERG (P = .27), maximal ERG (P = .65), or cone implicit time (no change over 4 years). The rate of cone loss (ie, event rate) was markedly reduced compared with rates in previous studies. No severe treatment-emergent adverse

Stream salamander species richness and abundance in relation to environmental factors in Shenandoah National Park, Virginia

USGS Publications Warehouse

Campbell Grant, Evan H.; Jung, Robin E.; Rice, Karen C.

2005-01-01

Stream salamanders are sensitive to acid mine drainage and may be sensitive to acidification and low acid neutralizing capacity (ANC) of a watershed. Streams in Shenandoah National Park, Virginia, are subject to episodic acidification from precipitation events. We surveyed 25 m by 2 m transects located on the stream bank adjacent to the water channel in Shenandoah National Park for salamanders using a stratified random sampling design based on elevation, aspect and bedrock geology. We investigated the relationships of four species (Eurycea bislineata, Desmognathus fuscus, D. monticola and Gyrinophilus porphyriticus) to habitat and water quality variables. We did not find overwhelming evidence that stream salamanders are affected by the acid-base status of streams in Shenandoah National Park. Desmognathus fuscus and D. monticola abundance was greater both in streams that had a higher potential to neutralize acidification, and in higher elevation (>700 m) streams. Neither abundance of E. bislineata nor species richness were related to any of the habitat variables. Our sampling method preferentially detected the adult age class of the study species and did not allow us to estimate population sizes. We suggest that continued monitoring of stream salamander populations in SNP will determine the effects of stream acidification on these taxa.

Abundance of western red-backed salamanders (Plethodon vehiculum) in the Washington Coast Range after headwater stream-buffer manipulation

Treesearch

Randall J. Wilk; Jeffrey D. Ricklefs; Martin G. Raphael

2014-01-01

We evaluated the effect of forest riparian alternative tree buffer designs on Western Red-backed Salamanders (Plethodon vehiculum) along headwater stream banks in managed forests of the Washington Coast Range. We used pit trap live removals in early autumn to estimate relative abundances of surface-active salamanders before and after 3 levels of riparian buffer...

Resource partitioning in two stream salamanders, Dicamptodon tenebrosus and Rhyacotriton cascadae, from the Oregon Cascade Mountains

USGS Publications Warehouse

Cudmore, Wynn W.; Bury, R. Bruce

2014-01-01

We investigated the potential for resource partitioning between the Coastal giant salamander (Dicamptodon tenebrosus) and the Cascade torrent salamander (Rhyacotriton cascadae) by examining their diet and microhabitats in forest streams. Larval D. tenebrosus and R. cascadae fed primarily upon aquatic insect larvae. We found similar foods in larval and adult R. cascadae and combined these results. Dicamptodon larvae consumed ephemeropteran, plecopteran, and trichopteran larvae in about equal amounts whereas R. cascadae ate more trichopteran and less ephemeropteran larvae than D. tenebrosus. Diet of all R. cascadae overlapped more with smaller than larger sized D. tenebrosus larvae. Comparisons of diets with available foods indicated R. cascadae is more selective or more gape-limited in its feeding habits than D. tenebrosus larvae. The two salamanders differed in use of microhabitats in creeks, which may contribute to their diet differences.

Ultrastructural changes in the receptor parts of retinal rods in experimental alloxan-induced diabetes in rabbits.

PubMed

Zarebska, A; Łańcut, M; Bakiera, K; Matejko, E; Czerny, K; Kiś, G; Wójtowicz, Z

2001-01-01

Mature rabbits were administered a single dose of alloxan at the dose 100 mg/kg b.m. After 3 and 6 weeks and after 3 and 6 months, the samples of the retina were taken from the areas immediate to the papilla of the optic nerve. Ultrathin sections were dyed according to the Reynold's method, and the receptive parts of the rods were examined under electron microscope BS-500 Tesla. After 6 weeks following alloxan administration, distinct morphological changes in the form of enlargement of certain discs in the receptive parts of rod cells were observed. After 3 months the majority of the discs was damaged, and after 6 months only single, quite well preserved rod cells were found to be present in the retina.

Mathematical Model of the Role of RdCVF in the Coexistence of Rods and Cones in a Healthy Eye.

PubMed

Camacho, Erika T; Léveillard, Thierry; Sahel, José-Alain; Wirkus, Stephen

2016-07-01

Understanding the essential components and processes for coexistence of rods and cones is at the forefront of retinal research. The recent discovery on RdCVF's mechanism and mode of action for enhancing cone survival brings us a step closer to unraveling key questions of coexistence and codependence of these neurons. In this work, we build from ecological and enzyme kinetic work on functional response kinetics and present a mathematical model that allows us to investigate the role of RdCVF and its contribution to glucose intake. Our model results and analysis predict a dual role of RdCVF for enhancing and repressing the healthy coexistence of the rods and cones. Our results show that maintaining RdCVF above a threshold value allows for coexistence. However, a significant increase above this value threatens the existence of rods as the cones become extremely efficient at uptaking glucose and begin to take most of it for themselves. We investigate the role of natural glucose intake and that due to RdCVF in both high and low nutrient levels. Our analysis reveals that under low nutrient levels coexistence is not possible regardless of the amount of RdCVF present. With high nutrient levels coexistence can be achieved with a relative small increase in glucose uptake. By understanding the contributions of rods to cones survival via RdCVF in a non-diseased retina, we hope to shed light on degenerative diseases such as retinitis pigmentosa.

Effect of Rhodopsin Phosphorylation on Dark Adaptation in Mouse Rods

PubMed Central

Berry, Justin; Frederiksen, Rikard; Yao, Yun; Nymark, Soile

2016-01-01

Rhodopsin is a prototypical G-protein-coupled receptor (GPCR) that is activated when its 11-cis-retinal moiety is photoisomerized to all-trans retinal. This step initiates a cascade of reactions by which rods signal changes in light intensity. Like other GPCRs, rhodopsin is deactivated through receptor phosphorylation and arrestin binding. Full recovery of receptor sensitivity is then achieved when rhodopsin is regenerated through a series of steps that return the receptor to its ground state. Here, we show that dephosphorylation of the opsin moiety of rhodopsin is an extremely slow but requisite step in the restoration of the visual pigment to its ground state. We make use of a novel observation: isolated mouse retinae kept in standard media for routine physiologic recordings display blunted dephosphorylation of rhodopsin. Isoelectric focusing followed by Western blot analysis of bleached isolated retinae showed little dephosphorylation of rhodopsin for up to 4 h in darkness, even under conditions when rhodopsin was completely regenerated. Microspectrophotometeric determinations of rhodopsin spectra show that regenerated phospho-rhodopsin has the same molecular photosensitivity as unphosphorylated rhodopsin and that flash responses measured by trans-retinal electroretinogram or single-cell suction electrode recording displayed dark-adapted kinetics. Single quantal responses displayed normal dark-adapted kinetics, but rods were only half as sensitive as those containing exclusively unphosphorylated rhodopsin. We propose a model in which light-exposed retinae contain a mixed population of phosphorylated and unphosphorylated rhodopsin. Moreover, complete dark adaptation can only occur when all rhodopsin has been dephosphorylated, a process that requires >3 h in complete darkness. SIGNIFICANCE STATEMENT G-protein-coupled receptors (GPCRs) constitute the largest superfamily of proteins that compose ∼4% of the mammalian genome whose members share a common membrane

Retinitis pigmentosa inversa with unilateral high myopia with fellow eye optic disc pitting.

PubMed

Sheth, Saumil; Rush, Ryan; Narayanan, Raja

2011-01-01

To report a possible rare association of bilateral retinitis pigmentosa inversa (RPI) with unilateral high myopia with fellow eye optic disc pitting. A 55-year-old man with a history of reduced vision in the right eye since childhood presented with gradually decreasing vision in the left eye. On examination, a -23.00 diopter refractive error and diffuse chorioretinal atrophy consistent with pathologic myopia was found in the right eye. An optic disc pit with posterior pole pigmentary alterations thought to be consequent to a previous neurosensory detachment was found in the left eye. Though the retinal arteriolar attenuation seen in both eyes with an inconsistent history of night blindness since childhood pointed towards the possibility of a concurrently existing rod or rod-cone dystrophy, the posterior pole pigmentary alterations characteristic of RPI were clearly masked by the above pathologies. Optical coherence tomography demonstrated prominent foveal atrophy and an optic disc pit in the left eye. Electroretinography (ERG) demonstrated moderately attenuated amplitudes with prolonged implicit times of rod and cone responses bilaterally. The patient was diagnosed with bilateral RPI and anisometropic amblyopia in the right eye. This report documents a unique constellation of findings which include bilateral RPI and unilateral high myopia with an optic disc pit in the fellow eye. An ERG confirmation of a dystrophic etiology should be sought in suspicious cases, especially when findings are masked by the concurrent presence of other pathologies.

Plethodon cinerius (eastern red-backed salamander) movement

USGS Publications Warehouse

Sterrett, Sean; Brand, Adrianne B,; Fields, William R.; Katz, Rachel A.; Grant, Evan H. Campbell

2015-01-01

Lungless salamanders (family Plethodontidae) are relatively sedentary and are presumed to have limited dispersal ability (Marsh et al. 2004. Ecology 85:3396–3405). Site fidelity in Plethodontidae is high, and individuals displaced 90 m return to home territories (Kleeberger and Werner 1982. Copeia 1982:409–415). Individuals defend territories (Jaeger et al. 1982. Anim. Behav. 30:490–496) and female home ranges have been estimated to be 24.34 m2 (Kleeberger and Werner 1982, op. cit.). Females may seek out suitable subsurface habitat to oviposit eggs, yet little is known about their maximum movement distances (Petranka 1998. Salamanders of the United States and Canada. Smithsonian Institution Press, Washington. 587 pp.).On 18 September 2014, a female P. cinereus (lead back morphotype; SVL = 44.68 mm; 0.89 g) was found under a coverboard during a standard sampling event and uniquely marked using visual implant elastomer at the S.O. Conte Anadromous Fish Research Center, Massachusetts, USA (42.59280°N, 72.58070°W, datum WGS84; elev. 74 m). This individual was subsequently recaptured at ~1500 h on 8 October 2014 under a coverboard within 3 m of the original capture location and then again ~1430 h on 16 October 2014 under a log, within the same forest patch, though in a 50 x 150 m area adjacent to the original study area. Because we found the marked salamander while collecting multiple individuals for a laboratory study, the exact recapture location of the marked individual is not known. However, the distance between the 8 October capture location and the nearest edge of the 16 October search area (i.e. 50 x 150 m) was 143 m, indicating a minimum movement distance. As far as we are aware, this is the longest recorded movement for P. cinereus by more than 53 m (Kleeberger and Werner 1982, op. cit.). This finding followed a rain event of 1.63 cm within 24 h and the second largest sustained rain event during October. The movement we observed may have been due to

Quantum Biometrics with Retinal Photon Counting

NASA Astrophysics Data System (ADS)

Loulakis, M.; Blatsios, G.; Vrettou, C. S.; Kominis, I. K.

2017-10-01

It is known that the eye's scotopic photodetectors, rhodopsin molecules, and their associated phototransduction mechanism leading to light perception, are efficient single-photon counters. We here use the photon-counting principles of human rod vision to propose a secure quantum biometric identification based on the quantum-statistical properties of retinal photon detection. The photon path along the human eye until its detection by rod cells is modeled as a filter having a specific transmission coefficient. Precisely determining its value from the photodetection statistics registered by the conscious observer is a quantum parameter estimation problem that leads to a quantum secure identification method. The probabilities for false-positive and false-negative identification of this biometric technique can readily approach 10-10 and 10-4, respectively. The security of the biometric method can be further quantified by the physics of quantum measurements. An impostor must be able to perform quantum thermometry and quantum magnetometry with energy resolution better than 10-9ℏ , in order to foil the device by noninvasively monitoring the biometric activity of a user.

Propulsive forces of mudskipper fins and salamander limbs during terrestrial locomotion: implications for the invasion of land.

PubMed

Kawano, Sandy M; Blob, Richard W

2013-08-01

The invasion of land was a pivotal event in vertebrate evolution that was associated with major appendicular modifications. Although fossils indicate that the evolution of fundamentally limb-like appendages likely occurred in aquatic environments, the functional consequences of using early digited limbs, rather than fins, for terrestrial propulsion have had little empirical investigation. Paleontological and experimental analyses both have led to the proposal of an early origin of "hind limb-driven" locomotion among tetrapods or their ancestors. However, the retention of a pectoral appendage that had already developed terrestrial adaptations has been proposed for some taxa, and few data are available from extant functional models that can provide a foundation for evaluating the relative contributions of pectoral and pelvic appendages to terrestrial support among early stem tetrapods. To examine these aspects of vertebrate locomotor evolution during the invasion of land, we measured three-dimensional ground reaction forces (GRFs) produced by isolated pectoral fins of mudskipper fishes (Periophthalmus barbarus) during terrestrial crutching, and compared these to isolated walking footfalls by the forelimbs and hind limbs of tiger salamanders (Ambystoma tigrinum), a species with subequally-sized limbs that facilitate comparisons to early tetrapods. Pectoral appendages of salamanders and mudskippers exhibited numerous differences in GRFs. Compared with salamander forelimbs, isolated fins of mudskippers bear lower vertical magnitudes of GRFs (as a proportion of body weight), and had GRFs that were oriented more medially. Comparing the salamanders' forelimbs and hind limbs, although the peak net GRF occurs later in stance for the forelimb, both limbs experience nearly identical mediolateral and vertical components of GRF, suggesting comparable contributions to support. Thus, forelimbs could also have played a significant locomotor role among basal tetrapods that had limbs

Effects of structural complexity enhancement on eastern red-backed salamander (Plethodon cinereus) populations in northern hardwood forests

USGS Publications Warehouse

McKenny, H.C.; Keeton, W.S.; Donovan, T.M.

2006-01-01

Managing for stand structural complexity in northern hardwood forests has been proposed as a method for promoting microhabitat characteristics important to eastern red-backed salamanders (Plethodon cinereus). We evaluated the effects of alternate, structure-based silvicultural systems on red-backed salamander populations at two research sites in northwestern Vermont. Treatments included two uneven-aged approaches (single-tree selection and group-selection) and one unconventional approach, termed "structural complexity enhancement" (SCE), that promotes development of late-successional structure, including elevated levels of coarse woody debris (CWD). Treatments were applied to 2 ha units and were replicated two to four times depending on treatment. We surveyed red-backed salamanders with a natural cover search method of transects nested within vegetation plots 1 year after logging. Abundance estimates corrected for detection probability were calculated from survey data with a binomial mixture model. Abundance estimates differed between study areas and were influenced by forest structural characteristics. Model selection was conducted using Akaike Information Criteria, corrected for over-dispersed data and small sample size (QAICc). We found no difference in abundance as a response to treatment as a whole, suggesting that all of the uneven-aged silvicultural systems evaluated can maintain salamander populations after harvest. However, abundance was tied to specific structural habitat attributes associated with study plots within treatments. The most parsimonious model of habitat covariates included site, relative density of overstory trees, and density of more-decayed and less-decayed downed CWD. Abundance responded positively to the density of downed, well-decayed CWD and negatively to the density of poorly decayed CWD and to overstory relative density. CWD volume was not a strong predictor of salamander abundance. We conclude that structural complexity enhancement

The effects of used motor oil, silt, and the water mold Saprolegnia parasitica on the growth and survival of mole salamanders (genus Ambystoma).

PubMed

Lefcort, H; Hancock, K A; Maur, K M; Rostal, D C

1997-05-01

Amphibians appear to be declining worldwide. One cause of their decline may be used crankcase oil which leaks from motor vehicles and washes into ponds. Once in ponds, the oil may either be directly toxic to amphibians, or may indirectly affect them by disrupting food chains. The effects of oil may also be compounded by naturally occurring materials in the water column such as silt. Silt may interfere with respiration across gill surfaces. This study examined the effects of oil and silt on the growth and metamorphosis of larval mole salamanders, Ambystoma opacum and A. tigrinum tigrinum. In Experiment One it examined ponds with and without silty water and oil pollution to determine their suitability as habitats for salamander larvae. In Experiment Two it studied the effects of low levels of oil combined with silt on animals raised in the laboratory and fed prey items not raised in oil. In Experiment Three, it explored the effects of oil at an ecosystem level by raising the salamanders in the field in plastic micromesocosms that mimicked small ponds. Finally, in Experiment Four, in the laboratory, it examined the short-term survival of salamanders in high concentrations of oil. This study found that ponds containing oil and silt produce salamanders of reduced size and weight. Furthermore, while salamanders are relatively robust to the short term effects of large concentrations of used motor oil, oil has deleterious effects on the community and therefore exerts an indirect negative effect on salamanders. In the mi- cro-mesocosms containing oil, salamanders were smaller and weighed less than animals not raised in oil. Furthermore, silt results in reduced growth, earlier metamorphosis, and increased susceptibility to the water mold Saprolegnia parasitica.

BDNF improves the efficacy ERG amplitude maintenance by transplantation of retinal stem cells in RCS rats.

PubMed

Tian, Chunyu; Weng, Chuan Chuang; Yin, Zheng Qin

2010-01-01

The aim of this study was to evaluate the efficacy of subretinal transplantation of rat retinal stem cell when combined with Brain-derived neurotrophic factor (BDNF) in a rat model of retinal degeneration - Royal College of Surgeons (RCS) rats. Retinal stem cells were derived from embryonic day 17 Long-Evans rats and pre-labeled with fluorescence pigment-DiI prior to transplant procedures. RCS rats received injections of retinal stem cells, stem cells+BDNF, phosphate buffered saline or BNDF alone (n = 3 eyes for each procedure). At 1, 2 and 3 months after transplantation, the electroretinogram (ERG) was assessed and the outer nuclear layer thickness measured. The eyes receiving retinal stem cell and stem cell+BDNF transplants showed better photoreceptor maintenance than the other groups (P < 0.01) at all time points. One month after retina transplantation, the amplitudes of rod-ERG and Max-ERG b waves were significantly higher the eyes with stem cells+BDNF (P < 0.01), however, this difference was not seen at two and three months post transplantation. BDNF treatment alone group (without transplanted cells) had no effect when compared to buffer injections. The present results indicate that BDNF can enhance the short-term efficacy of the retinal stem cell transplantation in treating retinal degenerative disease.

THE ORGANOPHOSPHOROUS INSECTICIDE FENTHION DOES NOT AFFECT PHAGOCYTOSIS OF ROD OUTER SEGMENTS BY RETINAL PIGMENT EPITHELIUM CELLS IN CULTURE.

EPA Science Inventory

:
Exposure to the organophosphorous insecticide fenthion has been associated with retinal degeneration in occupational studies. It has also been associated with pigmentary changes of the retina. Because retinal degeneration and pigmentary changes may be due to dysfunction of t...

Efficacy of riparian buffers in mitigating local populations declines and the effects of even-aged timber harvest on larval salamanders

Treesearch

William E Peterman; Raymond D. Semlitch

2009-01-01

Headwater streams are an important and prevalent feature of the eastern North American landscape.These streams provide a wealth of ecosystem services and support tremendous biological diversity, which is predominated by salamanders in the Appalachian region. Salamanders are ubiquitous throughout the region, contributing a significant...

Decline of disjunct green salamander (Aneides aeneus) populations in the southern appalachians

USGS Publications Warehouse

Corser, J.D.

2001-01-01

Coincident with other amphibians around the world Aneides aeneus, a terrestrial plethodontid salamander, suffered a population collapse in a disjunct portion of its range in the mid-late 1970s. Long-term monitoring of seven historical green salamander populations throughout the 1990s showed a 98% decline in relative abundance since 1970. Three out of six populations first discovered in 1991 also crashed in 1996-1997. The synchronized suddenness of the declines, their region-wide impact, and effects on both small and larger populations, suggest the role of a novel agent of mortality beginning in the mid-late 1970s. Acting alone, but more likely in concert, habitat loss, overcollecting, epidemic disease and climate change could account for this region-wide decline.

Intrinsically photosensitive retinal ganglion cells.

PubMed

Do, Michael Tri Hoang; Yau, King-Wai

2010-10-01

Life on earth is subject to alternating cycles of day and night imposed by the rotation of the earth. Consequently, living things have evolved photodetective systems to synchronize their physiology and behavior with the external light-dark cycle. This form of photodetection is unlike the familiar "image vision," in that the basic information is light or darkness over time, independent of spatial patterns. "Nonimage" vision is probably far more ancient than image vision and is widespread in living species. For mammals, it has long been assumed that the photoreceptors for nonimage vision are also the textbook rods and cones. However, recent years have witnessed the discovery of a small population of retinal ganglion cells in the mammalian eye that express a unique visual pigment called melanopsin. These ganglion cells are intrinsically photosensitive and drive a variety of nonimage visual functions. In addition to being photoreceptors themselves, they also constitute the major conduit for rod and cone signals to the brain for nonimage visual functions such as circadian photoentrainment and the pupillary light reflex. Here we review what is known about these novel mammalian photoreceptors.

Potential reduction in terrestrial salamander ranges associated with Marcellus shale development

USGS Publications Warehouse

Brand, Adrianne B,; Wiewel, Amber N. M.; Grant, Evan H. Campbell

2014-01-01

Natural gas production from the Marcellus shale is rapidly increasing in the northeastern United States. Most of the endemic terrestrial salamander species in the region are classified as ‘globally secure’ by the IUCN, primarily because much of their ranges include state- and federally protected lands, which have been presumed to be free from habitat loss. However, the proposed and ongoing development of the Marcellus gas resources may result in significant range restrictions for these and other terrestrial forest salamanders. To begin to address the gaps in our knowledge of the direct impacts of shale gas development, we developed occurrence models for five species of terrestrial plethodontid salamanders found largely within the Marcellus shale play. We predicted future Marcellus shale development under several scenarios. Under scenarios of 10,000, 20,000, and 50,000 new gas wells, we predict 4%, 8%, and 20% forest loss, respectively, within the play. Predictions of habitat loss vary among species, but in general, Plethodon electromorphus and Plethodonwehrlei are predicted to lose the greatest proportion of forested habitat within their ranges if future Marcellus development is based on characteristics of the shale play. If development is based on current well locations,Plethodonrichmondi is predicted to lose the greatest proportion of habitat. Models showed high uncertainty in species’ ranges and emphasize the need for distribution data collected by widespread and repeated, randomized surveys.

Retinal detachment and retinal holes in retinitis pigmentosa sine pigmento.

PubMed

Csaky, K; Olk, R J; Mahl, C F; Bloom, S M

1991-01-01

Retinal detachment and retinal holes in two family members with retinitis pigmentosa sine pigmento are reported. We believe these are the first such cases reported in the literature. We describe the presenting symptoms and management, including cryotherapy, scleral buckling procedure, and sulfur hexafluoride injection (SF6), resulting in stable visual acuity in one case and retinal reattachment and improved visual acuity in the other case.

Distribution of the Sonora Tiger Salamander (Ambystoma mavortium stebbinsi) in Mexico

USGS Publications Warehouse

Hossack, Blake R.; Muths, Erin L.; Rorabaugh, James C.; Lemos Espinal, Julio A.; Sigafus, Brent H.; Chambert, Thierry A.; Carreon Arroyo, Gerardo; Hurtado Felix, David; Toyos Martinez, Daniel; Jones, Thomas R.

2016-01-01

The Sonoran Tiger Salamander (Ambystoma mavortium stebbinsi Lowe, 1954) was listed as federally endangered in the USA in 1997 (USFWS 1997). In the USA, the distribution of A. mavortium stebbinsi is limited to the San Rafael Valley (approximately 567 km2), between the Sierra San Antonio (called the Patagonia Mountains in Arizona) and Huachuca Mountains, and south of the Canelo Hills, Arizona (Fig. 1). The USA listing was triggered by loss of natural wetland habitats, threats from invasive predators, frequent die-offs from disease, introgression with the introduced Barred Tiger Salamander (A. mavortium mavortium), and small range and number of breeding sites that increases susceptibility to stochastic events (USFWS 1997). Small population sizes and limited gene flow have caused inbreeding, which may further reduce population viability and the potential for recovery (Jones et al. 1988; Storfer et al. 2014). 

Effective delivery of recombinant proteins to rod photoreceptors via lipid nanovesicles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asteriti, Sabrina; Dal Cortivo, Giuditta; Pontelli, Valeria

2015-06-12

The potential of liposomes to deliver functional proteins in retinal photoreceptors and modulate their physiological response was investigated by two experimental approaches. First, we treated isolated mouse retinas with liposomes encapsulating either recoverin, an important endogenous protein operating in visual phototransduction, or antibodies against recoverin. We then intravitrally injected in vivo liposomes encapsulating either rhodamin B or recoverin and we investigated the distribution in retina sections by confocal microscopy. The content of liposomes was found to be released in higher amount in the photoreceptor layer than in the other regions of the retina and the functional effects of the release weremore » in line with the current model of phototransduction. Our study sets the basis for quantitative investigations aimed at assessing the potential of intraocular protein delivery via biocompatible nanovesicles, with promising implications for the treatment of retinal diseases affecting the photoreceptor layer. - Highlights: • Recombinant proteins encapsulated in nano-sized liposomes injected intravitreally reach retinal photoreceptors. • The phototransduction cascade in rods is modulated by the liposome content. • Mathematical modeling predicts the alteration of the photoresponses following liposome fusion.« less

Psychophysical Measurement of Rod and Cone Thresholds in Stargardt Disease with Full-Field Stimuli

PubMed Central

Collison, Frederick T.; Fishman, Gerald A.; McAnany, J. Jason; Zernant, Jana; Allikmets, Rando

2014-01-01

Purpose To investigate psychophysical thresholds in Stargardt disease with the full-field stimulus test (FST). Methods Visual acuity (VA), spectral-domain optical coherence tomography (SD-OCT), full-field electroretinogram (ERG), and FST measurements were made in one eye of 24 patients with Stargardt disease. Dark-adapted rod FST thresholds were measured with short-wavelength stimuli, and cone FST thresholds were obtained from the cone plateau phase of dark adaptation using long-wavelength stimuli. Correlation coefficients were calculated for FST thresholds versus macular thickness, VA and ERG amplitudes. Results Stargardt patient FST cone thresholds correlated significantly with VA, macular thickness, and ERG cone-response amplitudes (all P<0.01). The patients’ FST rod thresholds correlated with ERG rod-response amplitudes (P<0.01), but not macular thickness (P=0.05). All Stargardt disease patients with flecks confined to the macula and most of the patients with flecks extending outside of the macula had normal FST thresholds. All patients with extramacular atrophic changes had elevated FST cone thresholds and most had elevated FST rod thresholds. Conclusion FST rod and cone threshold elevation in Stargardt disease patients correlated well with measures of structure and function, as well as ophthalmoscopic retinal appearance. FST appears to be a useful tool for assessing rod and cone function in Stargardt disease. PMID:24695063

Biochemical Measurements of Free Opsin in Macular Degeneration Eyes: Examining the 11-CIS Retinal Deficiency Hypothesis of Delayed Dark Adaptation (An American Ophthalmological Society Thesis).

PubMed

Hanneken, Anne; Neikirk, Thomas; Johnson, Jennifer; Kono, Masahiro

2017-08-01

To test the hypothesis that delayed dark adaptation in patients with macular degeneration is due to an excess of free unliganded opsin (apo-opsin) and a deficiency of the visual chromophore, 11 -cis retinal, in rod outer segments. A total of 50 human autopsy eyes were harvested from donors with and without macular degeneration within 2-24 hrs. postmortem. Protocols were developed which permitted dark adaptation of normal human eyes after death and enucleation. Biochemical methods of purifying rod outer segments were optimized and the concentration of rhodopsin and apo-opsin was measured with UV-visible scanning spectroscopy. The presence of apo-opsin was calculated by measuring the difference in the rhodopsin absorption spectra before and after the addition of 11 -cis retinal. A total of 20 normal eyes and 16 eyes from donors with early, intermediate and advanced stages of macular degeneration were included in the final analysis. Dark adaptation was achieved by harvesting whole globes in low light, transferring into dark (light-proof) canisters and dissecting the globes using infrared light and image converters for visualization. Apo-opsin was readily detected in positive controls after the addition of 11 -cis retinal. Normal autopsy eyes showed no evidence of apo-opsin. Eyes with macular degeneration also showed no evidence of apo-opsin, regardless of the severity of disease. Methods have been developed to study dark adaptation in human autopsy eyes. Eyes with age-related macular degeneration do not show a deficiency of 11 -cis retinal or an excess of apo-opsin within rod outer segments.

Gestational Lead Exposure Selectively Decreases Retinal Dopamine Amacrine Cells and Dopamine Content in Adult Mice

PubMed Central

Fox, Donald A.; Hamilton, W. Ryan; Johnson, Jerry E.; Xiao, Weimin; Chaney, Shawntay; Mukherjee, Shradha; Miller, Diane B.; O’Callaghan, James P.

2011-01-01

Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was ≤1, ≤10, ~25 and ~40 µg/dL, respectively, on PN10 and by PN30 all were ≤1 µg/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. PMID:21703292

Advances in repairing the degenerate retina by rod photoreceptor transplantation☆

PubMed Central

Pearson, Rachael A.

2014-01-01

Despite very different aetiologies, age-related macular degeneration (AMD) and most inherited retinal disorders culminate in the same final common pathway, loss of the light-sensitive photoreceptors. There are few clinical treatments and none can reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. The past decade has seen a number of landmark achievements in this field, which together provide strong justification for continuing investigation into photoreceptor replacement strategies. These include proof of principle for restoring vision by rod-photoreceptor transplantation in mice with congenital stationary night blindness and advances in stem cell biology, which have led to the generation of complete optic structures in vitro from embryonic stem cells. The latter represents enormous potential for generating suitable and renewable donor cells with which to achieve the former. However, there are still challenges presented by the degenerating recipient retinal environment that must be addressed as we move to translating these technologies towards clinical application. PMID:24412415

Modeling the Flexural Rigidity of Rod Photoreceptors

PubMed Central

Haeri, Mohammad; Knox, Barry E.; Ahmadi, Aphrodite

2013-01-01

In vertebrate eyes, the rod photoreceptor has a modified cilium with an extended cylindrical structure specialized for phototransduction called the outer segment (OS). The OS has numerous stacked membrane disks and can bend or break when subjected to mechanical forces. The OS exhibits axial structural variation, with extended bands composed of a few hundred membrane disks whose thickness is diurnally modulated. Using high-resolution confocal microscopy, we have observed OS flexing and disruption in live transgenic Xenopus rods. Based on the experimental observations, we introduce a coarse-grained model of OS mechanical rigidity using elasticity theory, representing the axial OS banding explicitly via a spring-bead model. We calculate a bending stiffness of ∼105 nN⋅μm2, which is seven orders-of-magnitude larger than that of typical cilia and flagella. This bending stiffness has a quadratic relation to OS radius, so that thinner OS have lower fragility. Furthermore, we find that increasing the spatial frequency of axial OS banding decreases OS rigidity, reducing its fragility. Moreover, the model predicts a tendency for OS to break in bands with higher spring number density, analogous to the experimental observation that transgenic rods tended to break preferentially in bands of high fluorescence. We discuss how pathological alterations of disk membrane properties by mutant proteins may lead to increased OS rigidity and thus increased breakage, ultimately contributing to retinal degeneration. PMID:23442852

Enhancing the efficacy of AREDS antioxidants in light-induced retinal degeneration

PubMed Central

Wong, Paul; Markey, M.; Rapp, C. M.; Darrow, R. M.; Ziesel, A.

2017-01-01

Purpose Light-induced photoreceptor cell degeneration and disease progression in age-related macular degeneration (AMD) involve oxidative stress and visual cell loss, which can be prevented, or slowed, by antioxidants. Our goal was to test the protective efficacy of a traditional Age-related Eye Disease Study antioxidant formulation (AREDS) and AREDS combined with non-traditional antioxidants in a preclinical animal model of photooxidative retinal damage. Methods Male Sprague-Dawley rats were reared in a low-intensity (20 lux) or high-intensity (200 lux) cyclic light environment for 6 weeks. Some animals received a daily dietary supplement consisting of a small cracker infused with an AREDS antioxidant mineral mixture, AREDS antioxidants minus zinc, or zinc oxide alone. Other rats received AREDS combined with a detergent extract of the common herb rosemary, AREDS plus carnosic acid, zinc oxide plus rosemary, or rosemary alone. Antioxidant efficacy was determined by measuring retinal DNA levels 2 weeks after 6 h of intense exposure to white light (9,000 lux). Western blotting was used to determine visual cell opsin and arrestin levels following intense light treatment. Rhodopsin regeneration was determined after 1 h of exposure to light. Gene array analysis was used to determine changes in the expression of retinal genes resulting from light rearing environment or from antioxidant supplementation. Results Chronic high-intensity cyclic light rearing resulted in lower levels of rod and cone opsins, retinal S-antigen (S-ag), and medium wavelength cone arrestin (mCAR) than found for rats maintained in low cyclic light. However, as determined by retinal DNA, and by residual opsin and arrestin levels, 2 weeks after acute photooxidative damage, visual cell loss was greater in rats reared in low cyclic light. Retinal damage decreased with AREDS plus rosemary, or with zinc oxide plus rosemary whereas AREDS alone and zinc oxide alone (at their daily recommended levels

Effects of nitrogenous wastes on survival of the Barton Springs salamander (Eurycea sosorum).

PubMed

Crow, Justin C; Ostrand, Kenneth G; Forstner, Michael R J; Catalano, Matthew; Tomasso, Joseph R

2017-11-01

The objective of our study was to determine the acute toxicity of 3 common aquatic nitrogenous toxicants to the federally endangered Barton Springs salamander (Eurycea sosorum). Based on our findings, the 96-h median lethal concentrations (96-h LC50) for un-ionized ammonia-N, nitrite-N, and nitrate-N to E. sosorum are 2.0 ± 0.32, 31.7 ± 4.02, and 968.5 ± 150.6 mg/L, respectively. These results establish a benchmark for the tolerance of plethodontid salamanders to these toxicants and indicate that current water quality criteria are adequate for their protection. Environ Toxicol Chem 2017;36:3003-3007. © 2017 SETAC. © 2017 SETAC.

Development of Lead Hammerhead Ribozyme Candidates against Human Rod Opsin mRNA for Retinal Degeneration Therapy

PubMed Central

Abdelmaksoud, Heba E.; Yau, Edwin H.; Zuker, Michael; Sullivan, Jack M.

2011-01-01

To identify lead candidate allele-independent hammerhead ribozymes (hhRz) for the treatment of autosomal dominant mutations in the human rod opsin (RHO) gene, we tested a series of hhRzs for potential to significantly knockdown human RHO gene expression in a human cell expression system. Multiple computational criteria were used to select target mRNA regions likely to be single stranded and accessible to hhRz annealing and cleavage. Target regions are tested for accessibility in a human cell culture expression system where the hhRz RNA and target mRNA and protein are coexpressed. The hhRz RNA is embedded in an adenoviral VAI RNA chimeric RNA of established structure and properties which are critical to the experimental paradigm. The chimeric hhRz-VAI RNA is abundantly transcribed so that the hhRzs are expected to be in great excess over substrate mRNA. HhRz-VAI traffics predominantly to the cytoplasm to colocalize with the RHO mRNA target. Colocalization is essential for second-order annealing reactions. The VAI chimera protects the hhRz RNA from degradation and provides for a long half life. With cell lines chosen for high transfection efficiency and a molar excess of hhRz plasmid over target plasmid, the conditions of this experimental paradigm are specifically designed to evaluate for regions of accessibility of the target mRNA in cellulo. Western analysis was used to measure the impact of hhRz expression on RHO protein expression. Three lead candidate hhRz designs were identified that significantly knockdown target protein expression relative to control (p < 0.05). Successful lead candidates (hhRz CUC↓ 266, hhRz CUC↓ 1411, hhRz AUA↓ 1414) targeted regions of human RHO mRNA that were predicted to be accessible by a bioinformatics approach, whereas regions predicted to be inaccessible supported no knockdown. The maximum opsin protein level knockdown is approximately 30% over a 48 hr paradigm of testing. These results validate a rigorous computational

In search of critically endangered species: the current situation of two tiny salamander species in the Neotropical mountains of Mexico.

PubMed

Sandoval-Comte, Adriana; Pineda, Eduardo; Aguilar-López, José L

2012-01-01

Worldwide, one in every three species of amphibian is endangered, 39 species have gone extinct in the last 500 years and another 130 species are suspected to have gone extinct in recent decades. Of the amphibians, salamanders have the highest portion of their species in one of the risk categories, even higher than the frogs. To date there have been few studies that have used recent field data to examine the status of populations of endangered salamanders. In this study we evaluate the current situation of two tiny salamanders, Parvimolge townsendi and Thorius pennatulus, both of which are distributed at intermediate elevations in the mountains of the northern Neotropics and are considered to be critically endangered; the first has been proposed as possibly extinct. By carrying out exhaustive surveys in both historical and potentially suitable sites for these two species, we evaluated their abundance and the characteristics of their habitats, and we estimated their potential geographic distribution. We visited 22 sites, investing 672 person-hours of sampling effort in the surveys, and found 201 P. townsendi salamanders in 11 sites and only 13 T. pennatulus salamanders in 5 sites. Both species were preferentially found in cloud forest fragments that were well conserved or only moderately transformed, and some of the salamanders were found in shade coffee plantations. The potential distribution area of both species is markedly fragmented and we estimate that it has decreased by more than 48%. The results of this study highlight the importance of carrying out exhaustive, systematic field surveys to obtain accurate information about the current situation of critically endangered species, and help us better understand the crisis that amphibians are facing worldwide.

Influence of observers and stream flow on northern two-lined salamander (Eurycea bislineata bislineata) relative abundance estimates in Acadia and Shenandoah National Parks, USA

USGS Publications Warehouse

Crocker, J.B.; Bank, M.S.; Loftin, C.S.; Jung Brown, R.E.

2007-01-01

We investigated effects of observers and stream flow on Northern Two-Lined Salamander (Eurycea bislineata bislineata) counts in streams in Acadia (ANP) and Shenandoah National Parks (SNP). We counted salamanders in 22 ANP streams during high flow (May to June 2002) and during low flow (July 2002). We also counted salamanders in SNP in nine streams during high flow (summer 2003) and 11 streams during low flow (summers 2001?02, 2004). In 2002, we used a modified cover-controlled active search method with a first and second observer. In succession, observers turned over 100 rocks along five 1-m belt transects across the streambed. The difference between observers in total salamander counts was not significant. We counted fewer E. b. bislineata during high flow conditions, confirming that detection of this species is reduced during high flow periods and that assessment of stream salamander relative abundance is likely more reliable during low or base flow conditions.

Retinal oximetry in patients with ischaemic retinal diseases.

PubMed

Rilvén, Sandra; Torp, Thomas Lee; Grauslund, Jakob

2017-03-01

The retinal oximeter is a new tool for non-invasive measurement of retinal oxygen saturation in humans. Several studies have investigated the associations between retinal oxygen saturation and retinal diseases. In the present systematic review, we examine whether there are associations between retinal oxygen saturation and retinal ischaemic diseases. We used PubMed and Embase to search for retinal oxygen saturation and retinal ischaemic diseases. Three separate searches identified a total of 79 publications. After two levels of manual screening, 10 studies were included: six about diabetic retinopathy (DR) and four about retinal vein occlusion. No studies about retinal artery occlusion were included. In diabetes, all studies found that increases in retinal venous oxygen saturation (rvSatO 2 ) were associated with present as well as increasing levels of DR. Four of six studies also found increased retinal arterial oxygen saturation (raSatO 2 ) in patients with DR. In patients with central retinal vein occlusion (CRVO), all studies found that rvSatO 2 was reduced, but raSatO 2 remained unchanged. Branch retinal vein occlusion was not associated with changes in retinal oxygen saturation, but this was based on a single study. In conclusion, DR is associated with increased rvSatO 2 and might also be related to increased raSatO 2 . Central retinal vein occlusion (CRVO) is correlated with increased rvSatO 2 but unrelated to raSatO 2 . Prospective studies are needed to expand these findings. These would tell whether retinal oximetry could be a potential tool for screening or a biomarker of treatment outcome in patients with ischaemic retinal diseases. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Size-Mediated Tradeoffs in Life-History Traits in Dusky Salamanders

Treesearch

Richard C. Bruce

2013-01-01

Among salamanders of the genus Desmognathus, the larger species tend to be more aquatic and the smaller more terrestrial. I studied life histories in assemblages of Desmognathus in the southern Blue Ridge Mountains of North Carolina at sites in the Cowee and southern Nantahala Mountains. Traits evaluated included mortality/survival...

Spatial data for Eurycea salamander habitats associated With three aquifers in south-central Texas

USGS Publications Warehouse

Heitmuller, Franklin T.; Reece, Brian D.

2006-01-01

Eurycea salamander taxa comprise 12 known species that inhabit springs and caves in south-central Texas. Many of these are threatened or endangered species, and some are found only at one location. A number of the neotenic salamanders might be at risk from habitat loss associated with declines in ground-water levels. Eurycea salamander habitats are associated with three aquifers in south-central Texas: (1) the Edwards-Trinity (Plateau) aquifer, (2) the Edwards (Balcones Fault Zone) aquifer, and (3) the Trinity aquifer. The Edwards (Balcones fault zone) aquifer is commonly separated into three segments: from southwest to northeast, the San Antonio segment, the Barton Springs segment, and the northern segment. The Trinity aquifer south of the Colorado River can be divided into three permeable zones, the upper, middle, and lower zone. The U.S. Geological Survey, in cooperation with the U.S. Fish and Wildlife Service, developed this report (geodatabase) to aggregate the spatial data necessary to assess the potential effects of ground-water declines on known Eurycea habitat locations in south-central Texas. The geodatabase provides information about spring habitats, spring flow, cave habitats, aquifers, and projected water levels.

Safe caves and dangerous forests? Predation risk may contribute to salamander colonization of subterranean habitats

NASA Astrophysics Data System (ADS)

Salvidio, Sebastiano; Palumbi, Giulia; Romano, Antonio; Costa, Andrea

2017-04-01

Recent studies suggest that many organisms actively colonize the subterranean environment to avoid climatic stress, exploit new ecological opportunities and reduce competition and predation. Terrestrial salamanders are known to colonize the more stable subterranean habitats mainly to escape external climatic extremes, while the role of predation avoidance remains untested. To better understand the importance of predation, we used clay models of the cave salamander Speleomantes strinatii to compare the predation occurring in woodland and subterranean habitats. Models were positioned in three forests and in three caves in NW Italy. One-hundred eighty-four models were retrieved from the field and 59 (32%) were attacked by predators. Models were attacked on their head more often than expected by chance and, therefore, were perceived by predators as real prey items. In the woodlands, clay models showed a four-time higher probability of being attacked in comparison to caves, suggesting a different level of potential predation risk in these surface habitats. These findings are one of the first experimental evidences that, in terrestrial ecosystems, predation avoidance may contribute to the salamander underground colonization process.

Dose rate estimation of the Tohoku hynobiid salamander, Hynobius lichenatus, in Fukushima.

PubMed

Fuma, Shoichi; Ihara, Sadao; Kawaguchi, Isao; Ishikawa, Takahiro; Watanabe, Yoshito; Kubota, Yoshihisa; Sato, Youji; Takahashi, Hiroyuki; Aono, Tatsuo; Ishii, Nobuyoshi; Soeda, Haruhi; Matsui, Kumi; Une, Yumi; Minamiya, Yukio; Yoshida, Satoshi

2015-05-01

The radiological risks to the Tohoku hynobiid salamanders (class Amphibia), Hynobius lichenatus due to the Fukushima Dai-ichi Nuclear Power Plant accident were assessed in Fukushima Prefecture, including evacuation areas. Aquatic egg clutches (n = 1 for each sampling date and site; n = 4 in total), overwintering larvae (n = 1-5 for each sampling date and site; n = 17 in total), and terrestrial juveniles or adults (n = 1 or 3 for each sampling date and site; n = 12 in total) of H. lichenatus were collected from the end of April 2011 to April 2013. Environmental media such as litter (n = 1-5 for each sampling date and site; n = 30 in total), soil (n = 1-8 for each sampling date and site; n = 31 in total), water (n = 1 for each sampling date and site; n = 17 in total), and sediment (n = 1 for each sampling date and site; n = 17 in total) were also collected. Activity concentrations of (134)Cs + (137)Cs were 1.9-2800, 0.13-320, and 0.51-220 kBq (dry kg) (-1) in the litter, soil, and sediment samples, respectively, and were 0.31-220 and <0.29-40 kBq (wet kg)(-1) in the adult and larval salamanders, respectively. External and internal absorbed dose rates to H. lichenatus were calculated from these activity concentration data, using the ERICA Assessment Tool methodology. External dose rates were also measured in situ with glass dosimeters. There was agreement within a factor of 2 between the calculated and measured external dose rates. In the most severely contaminated habitat of this salamander, a northern part of Abukuma Mountains, the highest total dose rates were estimated to be 50 and 15 μGy h(-1) for the adults and overwintering larvae, respectively. Growth and survival of H. lichenatus was not affected at a dose rate of up to 490 μGy h(-1) in the previous laboratory chronic gamma-irradiation experiment, and thus growth and survival of this salamander would not be affected, even in the most severely contaminated habitat in Fukushima Prefecture. However, further

Morphological changes in the anterior segment of the Abyssinian cat eye with hereditary rod-cone degeneration.

PubMed

May, Chr Albrecht; Lütjen-Drecoll, Elke; Narfström, Kristina

2005-10-01

The purpose of this study was to investigate morphological changes of the anterior segment of the eye in Abyssinian cats with progressive rod-cone degeneration and to correlate them with blood flow data obtained in the same animals. Sections of the left eyes of six normal cats and of eight cats with different stages of hereditary retinal degeneration were prepared for transmission and scanning electron microscopy. Tangential and sagittal sections were also stained with antibodies against substance P, tyrosine hydroxylase, panneuronal marker PGP9.5, nitric oxide synthase, synaptophysin, and smooth muscle alpha-actin. In Abyssinian cats with hereditary rod-cone degeneration, significant changes were observed in the iris consisting of irregularities in the vascular wall of smaller arteries without changes in their innervation pattern. The ciliary processes were shorter than in normal cats, and their structure appeared more compact and retracted. Slight changes were also observed in the anterior part of the ciliary epithelium. The anterior chamber angle region did not appear to be affected. Clear morphological correlations to the physiological blood flow data were observed in the anterior eye segment, pointing not only to functional but also morphological vascular abnormalities in this animal model for retinitis pigmentosa.

The effect of waist twisting on walking speed of an amphibious salamander like robot

NASA Astrophysics Data System (ADS)

Yin, Xin-Yan; Jia, Li-Chao; Wang, Chen; Xie, Guang-Ming

2016-06-01

Amphibious salamanders often swing their waist to coordinate quadruped walking in order to improve their crawling speed. A robot with a swing waist joint, like an amphibious salamander, is used to mimic this locomotion. A control method is designed to allow the robot to maintain the rotational speed of its legs continuous and avoid impact between its legs and the ground. An analytical expression is established between the amplitude of the waist joint and the step length. Further, an optimization amplitude is obtained corresponding to the maximum stride. The simulation results based on automatic dynamic analysis of mechanical systems (ADAMS) and physical experiments verify the rationality and validity of this expression.

Superficial retinal precipitates in patients with syphilitic retinitis.

PubMed

Fu, Evelyn X; Geraets, Ryan L; Dodds, Emilio M; Echandi, Laura V; Colombero, Daniel; McDonald, H Richard; Jumper, J Michael; Cunningham, Emmett T

2010-01-01

The purpose of this study was to describe the occurrence of superficial retinal precipitates in patients with syphilitic retinitis. This was a retrospective, observational case series of nine eyes of eight patients with syphilitic retinitis associated with superficial retinal precipitates. The clinical, photographic, angiographic, and laboratory records were reviewed. Characteristics and treatment response of these superficial retinal precipitates were observed. All patients were Caucasian men, including 5 men who have sex with men (62.5%) and 6 (75.0%) who were positive for human immunodeficiency virus. None of the patients were previously diagnosed with syphilis. All patients developed panuveitis and a distinctly diaphanous or ground-glass retinitis associated with creamy yellow superficial retinal precipitates. In 3 patients (37.5%), the retinitis had a distinctive wedge-shaped appearance. Five patients (62.5%) had associated retinal vasculitis, 3 (37.5%) had serous retinal detachment, 2 (22.2%) had intraretinal hemorrhage, and 2 (22.2%) had papillitis. Within 2 weeks of initiating intravenous penicillin treatment, 7 patients (87.5%) experienced visual recovery to >or= 20/40. All affected eyes showed rapid resolution of clinical signs with minimal alternations of the retinal pigment epithelium in areas of prior retinitis after completion of antibiotic therapy. Characteristic superficial retinal precipitates may occur over areas of syphilitic retinitis. Improved recognition of this highly suggestive clinical sign may aid in early diagnosis and treatment.

Mechanics of lung ventilation in a large aquatic salamander, siren lacertina

PubMed

Brainerd; j

1998-06-01

Lung ventilation in Siren lacertina was studied using X-ray video, measurements of body cavity pressure and electromyography of hypaxial muscles. S. lacertina utilizes a two-stroke buccal pump in which mixing of expired and inspired gas is minimized by partial expansion of the buccal cavity during exhalation and then full expansion after exhalation is complete. Mixing is further reduced by the use of one or two accessory inspirations after the first, mixed-gas cycle. Exhalation occurs in two phases: a passive phase in which hydrostatic pressure and possibly lung elasticity force air out of the lungs, and an active phase in which contraction of the transverse abdominis (TA) muscle increases body cavity pressure and forces most of the remaining air out. In electromyograms of the lateral hypaxial musculature, the TA became active 200-400 ms before the rise in body cavity pressure, and activity ceased at peak pressure. The TA was not active during inspiration, and no consistent activity during breathing was noted in the external oblique, internal oblique and rectus abdominis muscles. The finding that the TA is the primary expiratory muscle in S. lacertina agrees with findings in a previous study of another salamander, Necturus maculosus. Together, these results indicate that the use of the TA for exhalation is a primitive character for salamanders and support the hypothesis that the breathing mechanism of salamanders represents an intermediate step in evolution between a buccal pump, in which only head muscles are used for ventilation, and an aspiration pump, in which axial muscles are used for both exhalation and inhalation.

Microbial community dynamics and effect of environmental microbial reservoirs on red-backed salamanders (Plethodon cinereus)

PubMed Central

Loudon, Andrew H; Woodhams, Douglas C; Parfrey, Laura Wegener; Archer, Holly; Knight, Rob; McKenzie, Valerie; Harris, Reid N

2014-01-01

Beneficial cutaneous bacteria on amphibians can protect against the lethal disease chytridiomycosis, which has devastated many amphibian species and is caused by the fungus Batrachochytrium dendrobatidis. We describe the diversity of bacteria on red-backed salamanders (Plethodon cinereus) in the wild and the stability of these communities through time in captivity using culture-independent Illumina 16S rRNA gene sequencing. After field sampling, salamanders were housed with soil from the field or sterile media. The captive conditions led to different trajectories of bacterial communities. Eight OTUs present on >90% of salamanders in the field, through time, and in both treatments were defined as the core community, suggesting that some bacteria are closely associated with the host and are independent of an environmental reservoir. One of these taxa, a Pseudomonas sp., was previously cultured from amphibians and found to be antifungal. As all host-associated bacteria were found in the soil reservoir, environmental microbes strongly influence host–microbial diversity and likely regulate the core community. Using PICRUSt, an exploratory bioinformatics tool to predict gene functions, we found that core skin bacteria provided similar gene functions to the entire community. We suggest that future experiments focus on testing whether core bacteria on salamander skin contribute to the observed resistance to chytridiomycosis in this species even under hygenic captive conditions. For disease-susceptible hosts, providing an environmental reservoir with defensive bacteria in captive-rearing programs may improve outcomes by increasing bacterial diversity on threatened amphibians or increasing the likelihood that defensive bacteria are available for colonization. PMID:24335825

Elevation, aspect, and cove size effects on southern Appalachian salamanders

Treesearch

W. Mark Ford; Michael A. Menzel; Richard H. Odom

2002-01-01

Using museum collection records and variables computed by digital terrain modeling in a geographic information system, we examined the relationship of elevation, aspect, and "cove" patch size to the presence or absence of 7 common woodland salamanders in mature cove hardwood and northern hardwood forests in the southern Appalachians of Georgia, North Carolina...

Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy.

PubMed

Katschke, Kenneth J; Xi, Hongkang; Cox, Christian; Truong, Tom; Malato, Yann; Lee, Wyne P; McKenzie, Brent; Arceo, Rommel; Tao, Jianhua; Rangell, Linda; Reichelt, Mike; Diehl, Lauri; Elstrott, Justin; Weimer, Robby M; Campagne, Menno van Lookeren

2018-05-09

Geographic atrophy (GA), the advanced form of dry age-related macular degeneration (AMD), is characterized by progressive loss of retinal pigment epithelium cells and photoreceptors in the setting of characteristic extracellular deposits and remains a serious unmet medical need. While genetic predisposition to AMD is dominated by polymorphisms in complement genes, it remains unclear how complement activation contributes to retinal atrophy. Here we demonstrate that complement is activated on photoreceptor outer segments (POS) in the retina peripheral to atrophic lesions associated with GA. When exposed to human serum following outer blood-retinal barrier breakdown, POS act as potent activators of the classical and alternative complement pathway. In mouse models of retinal degeneration, classical and alternative pathway complement activation on photoreceptors contributed to the loss of photoreceptor function. This was dependent on C5a-mediated recruitment of peripheral blood monocytes but independent of resident microglia. Genetic or pharmacologic inhibition of both classical and alternative complement C3 and C5 convertases was required to reduce progressive degeneration of photoreceptor rods and cones. Our study implicates systemic classical and alternative complement proteins and peripheral blood monocytes as critical effectors of localized retinal degeneration with potential relevance for the contribution of complement activation to GA.

Metals, Parasites, and Environmental Conditions Affecting Breeding Populations of Spotted Salamanders (Ambystoma maculatum) in Northern Arkansas, USA.

PubMed

DeMali, Heather M; Trauth, Stanley E; Bouldin, Jennifer L

2016-06-01

The spotted salamander (Ambystoma maculatum) is indigenous to northern Arkansas, and several breeding sites are known to exist in the region. Spotted salamanders (n = 17) were collected and examined for parasites and only three females harbored nematodes (Physaloptera spp.). Chronic aquatic bioassays were conducted using water collected from eight breeding ponds during different hydroperiod events. No lethal or sublethal effects were measured in Ceriodaphnia dubia; however, decreased growth and survival were seen in Pimephales promelas. Aqueous, sediment, and salamander hepatic samples were analyzed for As, Cd, Cu, Pb, and Ni. Metal analysis revealed possible increased metal exposure following precipitation, with greatest metal concentrations measured in sediment samples. Hepatic metal concentrations were similar in parasitized and non-parasitized individuals, and greatest Pb concentrations were measured following normal precipitation events. Determining environmental stressors of amphibians, especially during their breeding and subsequent larval life stage, is imperative to improve species conservation.

Genomic evidence for rod monochromacy in sloths and armadillos suggests early subterranean history for Xenarthra

PubMed Central

Emerling, Christopher A.; Springer, Mark S.

2015-01-01

Rod monochromacy is a rare condition in vertebrates characterized by the absence of cone photoreceptor cells. The resulting phenotype is colourblindness and low acuity vision in dim-light and blindness in bright-light conditions. Early reports of xenarthrans (armadillos, sloths and anteaters) suggest that they are rod monochromats, but this has not been tested with genomic data. We searched the genomes of Dasypus novemcinctus (nine-banded armadillo), Choloepus hoffmanni (Hoffmann's two-toed sloth) and Mylodon darwinii (extinct ground sloth) for retinal photoreceptor genes and examined them for inactivating mutations. We performed PCR and Sanger sequencing on cone phototransduction genes of 10 additional xenarthrans to test for shared inactivating mutations and estimated the timing of inactivation for photoreceptor pseudogenes. We concluded that a stem xenarthran became an long-wavelength sensitive-cone monochromat following a missense mutation at a critical residue in SWS1, and a stem cingulate (armadillos, glyptodonts and pampatheres) and stem pilosan (sloths and anteaters) independently acquired rod monochromacy early in their evolutionary history following the inactivation of LWS and PDE6C, respectively. We hypothesize that rod monochromacy in armadillos and pilosans evolved as an adaptation to a subterranean habitat in the early history of Xenarthra. The presence of rod monochromacy has major implications for understanding xenarthran behavioural ecology and evolution. PMID:25540280

Ballistic tongue projection in a miniaturized salamander.

PubMed

Deban, Stephen M; Bloom, Segall V

2018-05-20

Miniaturization of body size is often accompanied by peculiarities in morphology that can have functional consequences. We examined the feeding behavior and morphology of the miniaturized plethodontid salamander Thorius, one of the smallest vertebrates, to determine if its performance and biomechanics differ from those of its larger relatives. High-speed imaging and dynamics analysis of feeding at a range of temperatures show that tongue projection in Thorius macdougalli is ballistic and achieves accelerations of up to 600 G with low thermal sensitivity, indicating that tongue projection is powered by an elastic-recoil mechanism. Preceding ballistic projection is an unusual preparatory phase of tongue protrusion, which, like tongue retraction, shows lower performance and higher thermal sensitivity that are indicative of movement being powered directly by muscle shortening. The variability of tongue-projection kinematics and dynamics is comparable to larger ballistic-tongued plethodontids and reveals that Thorius is capable of modulating its tongue movements in response to prey distance. Morphological examination revealed that T. macdougalli possesses a reduced number of myofibers in the tongue muscles, a large projector muscle mass relative to tongue mass, and an unusual folding of the tongue skeleton, compared with larger relatives. Nonetheless, T. macdougalli retains the elaborated collagen aponeuroses in the projector muscle that store elastic energy and a tongue skeleton that is free of direct myofiber insertion, two features that appear to be essential for ballistic tongue projection in salamanders. © 2018 Wiley Periodicals, Inc.

A Distinct Phenotype of Eyes Shut Homolog (EYS)-Retinitis Pigmentosa Is Associated With Variants Near the C-Terminus.

PubMed

Sengillo, Jesse D; Lee, Winston; Nagasaki, Takayuki; Schuerch, Kaspar; Yannuzzi, Lawrence A; Freund, K Bailey; Sparrow, Janet R; Allikmets, Rando; Tsang, Stephen H

2018-06-01

Mutations in the eyes shut homolog (EYS) gene are a frequent cause of autosomal recessive retinitis pigmentosa (arRP). This study used multimodal retinal imaging to elucidate genotype-phenotype correlations in EYS-related RP (EYS-RP). Cross-sectional study. Multimodal retinal imaging and electrophysiologic testing were assessed for 16 patients with genetic confirmation of EYS-RP. A total of 27 unique EYS variants were identified in 16 patients. Seven patients presented with an unusual crescent-shaped hyperautofluorescent (hyperAF) ring on fundus autofluorescence (FAF) imaging encompassing a large nasal-superior area of the posterior pole. Three patients had a typical circular or oval perifoveal hyperAF ring and 6 patients had no hyperAF ring. Spectral-domain (SD) and en face optical coherence tomography (OCT) showed preserved ellipsoid zone and retinal thickness spatially corresponding to areas within the hyperAF rings. Eleven patients presented with a rod-cone dystrophy on full-field electroretinogram (ffERG), 1 patient presented with cone-rod dystrophy, and 4 patients did not undergo ffERG testing. A significant spatial association was found between EYS variant position and FAF phenotype, with variants occurring at a nucleotide position greater than GRCh37 6:65300137 (c.5617C) being more associated with patients exhibiting hyperAF rings at presentation. EYS-RP is a heterogeneous manifestation. Variants occurring in positions closer to the C-terminus of EYS are more common in patients presenting with hyperAF rings on FAF imaging. Copyright © 2018 Elsevier Inc. All rights reserved.

Rod electrical coupling is controlled by a circadian clock and dopamine in mouse retina

PubMed Central

Jin, Nan Ge; Chuang, Alice Z; Masson, Philippe J; Ribelayga, Christophe P

2015-01-01

Key points Rod photoreceptors play a key role in vision in dim light; in the mammalian retina, although rods are anatomically connected or coupled by gap junctions, a type of electrical synapse, the functional importance and regulation of rod coupling has remained elusive. We have developed a new technique in the mouse: perforated patch-clamp recording of rod inner segments in isolated intact retinae maintained by superfusion. We find that rod electrical coupling is controlled by a circadian clock and dopamine, and is weak during the day and stronger at night. The results also indicate that the signal-to-noise ratio for a dim light response is increased at night because of coupling. Our observations will provide a framework for understanding the daily variations in human vision as well as the basis of specific retinal malfunctions. Abstract Rod single-photon responses are critical for vision in dim light. Electrical coupling via gap junction channels shapes the light response properties of vertebrate photoreceptors, but the regulation of rod coupling and its impact on the single-photon response have remained unclear. To directly address these questions, we developed a perforated patch-clamp recording technique and recorded from single rod inner segments in isolated intact neural mouse retinae, maintained by superfusion. Experiments were conducted at different times of the day or under constant environmental conditions, at different times across the circadian cycle. We show that rod electrical coupling is regulated by a circadian clock and dopamine, so that coupling is weak during the day and strong at night. Altogether, patch-clamp recordings of single-photon responses in mouse rods, tracer coupling, receptive field measurements and pharmacological manipulations of gap junction and dopamine receptor activity provide compelling evidence that rod coupling is modulated in a circadian manner. These data are consistent with computer modelling. At night, single

Scanning laser densitometry and color perimetry demonstrate reduced photopigment density and sensitivity in two patients with retinal degeneration.

PubMed

Tornow, R P; Stilling, R; Zrenner, E

1999-10-01

To test the feasibility of scanning laser densitometry with a modified Rodenstock scanning laser ophthalmoscope (SLO) to measure the rod and cone photopigment distribution in patients with retinal diseases. Scanning laser densitometry was performed using a modified Rodenstock scanning laser ophthalmoscope. The distribution of the photopigments was calculated from dark adapted and bleached images taken with the 514 nm laser of the SLO. This wavelength is absorbed by rod and cone photopigments. Discrimination is possible due to their different spatial distribution. Additionally, to measure retinal sensitivity profiles, dark adapted two color static perimetry with a Tübinger manual perimeter was performed along the horizontal meridian with 1 degree spacing. A patient with retinitis pigmentosa had slightly reduced photopigment density within the central +/- 5 degrees but no detectable photopigment for eccentricities beyond 5 degrees. A patient with cone dystrophy had nearly normal pigment density beyond +/- 5 degrees, but considerably reduced photopigment density within the central +/- 5 degrees. Within the central +/- 5 degrees, the patient with retinitis pigmentosa had normal sensitivity for the red stimulus and reduced sensitivity for the green stimulus. There was no measurable function beyond 7 degrees. The patient with cone dystrophy had normal sensitivity for the green stimulus outside the foveal center and reduced sensitivity for the red stimulus at the foveal center. The results of color perimetry for this patient with a central scotoma were probably influenced by eccentric fixation. Scanning laser densitometry with a modified Rodenstock SLO is a useful method to assess the human photopigment distribution. Densitometry results were confirmed by dark adapted two color static perimetry. Photopigment distribution and retinal sensitivity profiles can be measured with high spatial resolution. This may help to measure exactly the temporal development of retinal

Conservation genetics of the endangered Shenandoah salamander (Plethodon shenandoah, Plethodontidae)

USGS Publications Warehouse

Carpenter, D.W.; Jung, R.E.; Sites, J.W.

2001-01-01

The Shenandoah salamander (Plethodon shenandoah) is restricted to three isolated talus outcrops in Shenandoah National Park, VA, USA and has one of the smallest ranges of any tetrapod vertebrate. This species was listed as endangered under the US Endangered Species Act in 1989 over concern that direct competition with the red-backed salamander (Plethodon cinereus), successional habitat changes, and human impacts may cause its decline and possible extinction. We address two issues herein: (1) whether extensive introgression (through long-term hybridization) is present between the two species and threatens the survival of P. shenandoah, and (2) the level of population structure within P. shenandoah. We provide evidence from mtDNA haplotypes that shows no genetic differentiation among the three isolates of P. shenandoah, suggesting that their fragmentation is a geologically recent event, and/or that the isolates are still connected by occasional gene flow. There is also no evidence for extensive introgression of alleles in either direction between P. cinereus and P. shenandoah, which suggests that P. shenandoah may not be in danger of being genetically swamped out through hybridization with P. cinereus.

Adaptation of cone pigments found in green rods for scotopic vision through a single amino acid mutation

PubMed Central

Kojima, Keiichi; Matsutani, Yuki; Yamashita, Takahiro; Yanagawa, Masataka; Imamoto, Yasushi; Yamano, Yumiko; Wada, Akimori; Hisatomi, Osamu; Nishikawa, Kanto; Sakurai, Keisuke; Shichida, Yoshinori

2017-01-01

Most vertebrate retinas contain a single type of rod for scotopic vision and multiple types of cones for photopic and color vision. The retinas of certain amphibian species uniquely contain two types of rods: red rods, which express rhodopsin, and green rods, which express a blue-sensitive cone pigment (M1/SWS2 group). Spontaneous activation of rhodopsin induced by thermal isomerization of the retinal chromophore has been suggested to contribute to the rod’s background noise, which limits the visual threshold for scotopic vision. Therefore, rhodopsin must exhibit low thermal isomerization rate compared with cone visual pigments to adapt to scotopic condition. In this study, we determined whether amphibian blue-sensitive cone pigments in green rods exhibit low thermal isomerization rates to act as rhodopsin-like pigments for scotopic vision. Anura blue-sensitive cone pigments exhibit low thermal isomerization rates similar to rhodopsin, whereas Urodela pigments exhibit high rates like other vertebrate cone pigments present in cones. Furthermore, by mutational analysis, we identified a key amino acid residue, Thr47, that is responsible for the low thermal isomerization rates of Anura blue-sensitive cone pigments. These results strongly suggest that, through this mutation, anurans acquired special blue-sensitive cone pigments in their green rods, which could form the molecular basis for scotopic color vision with normal red rods containing green-sensitive rhodopsin. PMID:28484015

Peripherin-2 couples rhodopsin to the CNG channel in outer segments of rod photoreceptors.

PubMed

Becirovic, Elvir; Nguyen, O N Phuong; Paparizos, Christos; Butz, Elisabeth S; Stern-Schneider, Gabi; Wolfrum, Uwe; Hauck, Stefanie M; Ueffing, Marius; Wahl-Schott, Christian; Michalakis, Stylianos; Biel, Martin

2014-11-15

Outer segments (OSs) of rod photoreceptors are cellular compartments specialized in the conversion of light into electrical signals. This process relies on the light-triggered change in the intracellular levels of cyclic guanosine monophosphate, which in turn controls the activity of cyclic nucleotide-gated (CNG) channels in the rod OS plasma membrane. The rod CNG channel is a macromolecular complex that in its core harbors the ion-conducting CNGA1 and CNGB1a subunits. To identify additional proteins of the complex that interact with the CNGB1a core subunit, we applied affinity purification of mouse retinal proteins followed by mass spectrometry. In combination with in vitro and in vivo co-immunoprecipitation and fluorescence resonance energy transfer (FRET), we found that the tetraspanin peripherin-2 links CNGB1a to the light-detector rhodopsin. Using immunoelectron microscopy, we found that this peripherin-2/rhodopsin/CNG channel complex localizes to the contact region between the disk rims and the plasma membrane. FRET measurements revealed that the fourth transmembrane domain (TM4) of peripherin-2 is required for the interaction with rhodopsin. Quantitatively, the binding affinity of the peripherin-2/rhodopsin interaction was in a similar range as that observed for rhodopsin dimers. Finally, we demonstrate that the p.G266D retinitis pigmentosa mutation found within TM4 selectively abolishes the binding of peripherin-2 to rhodopsin. This finding suggests that the specific disruption of the rhodopsin/peripherin-2 interaction in the p.G266D mutant might contribute to the pathophysiology in affected persons. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Gestational lead exposure selectively decreases retinal dopamine amacrine cells and dopamine content in adult mice.

PubMed

Fox, Donald A; Hamilton, W Ryan; Johnson, Jerry E; Xiao, Weimin; Chaney, Shawntay; Mukherjee, Shradha; Miller, Diane B; O'Callaghan, James P

2011-11-01

Gestational lead exposure (GLE) produces supernormal scotopic electroretinograms (ERG) in children, monkeys and rats, and a novel retinal phenotype characterized by an increased number of rod photoreceptors and bipolar cells in adult mice and rats. Since the loss of dopaminergic amacrine cells (DA ACs) in GLE monkeys and rats contributes to supernormal ERGs, the retinal DA system was analyzed in mice following GLE. C57BL/6 female mice were exposed to low (27 ppm), moderate (55 ppm) or high (109 ppm) lead throughout gestation and until postnatal day 10 (PN10). Blood [Pb] in control, low-, moderate- and high-dose GLE was ≤ 1, ≤ 10, ~25 and ~40 μg/dL, respectively, on PN10 and by PN30 all were ≤ 1 μg/dL. At PN60, confocal-stereology studies used vertical sections and wholemounts to characterize tyrosine hydroxylase (TH) expression and the number of DA and other ACs. GLE dose-dependently and selectively decreased the number of TH-immunoreactive (IR) DA ACs and their synaptic plexus without affecting GABAergic, glycinergic or cholinergic ACs. Immunoblots and confocal revealed dose-dependent decreases in retinal TH protein expression and content, although monoamine oxidase-A protein and gene expression were unchanged. High-pressure liquid chromatography showed that GLE dose-dependently decreased retinal DA content, its metabolites and DA utilization/release. The mechanism of DA selective vulnerability is unknown. However, a GLE-induced loss/dysfunction of DA ACs during development could increase the number of rods and bipolar cells since DA helps regulate neuronal proliferation, whereas during adulthood it could produce ERG supernormality as well as altered circadian rhythms, dark/light adaptation and spatial contrast sensitivity. Copyright © 2011 Elsevier Inc. All rights reserved.

Dietary Supplement Enriched in Antioxidants and Omega-3 Protects from Progressive Light-Induced Retinal Degeneration

PubMed Central

Ramchani-Ben Othman, Khaoula; Cercy, Christine; Amri, Mohamed; Doly, Michel; Ranchon-Cole, Isabelle

2015-01-01

In the present study, we have evaluated one of the dietary supplements enriched with antioxidants and fish oil used in clinical care for patient with age-related macular degeneration. Rats were orally fed by a gastric canula daily with 0.2 ml of water or dietary supplement until they were sacrificed. After one week of treatment, animals were either sacrificed for lipid analysis in plasma and retina, or used for evaluation of rod-response recovery by electroretinography (ERG) followed by their sacrifice to measure rhodopsin content, or used for progressive light-induced retinal degeneration (PLIRD). For PLIRD, animals were transferred to bright cyclic light for one week. Retinal damage was quantified by ERG, histology and detection of apoptotic nuclei. Animals kept in dim-cyclic-light were processed in parallel. PLIRD induced a thinning of the outer nuclear layer and a reduction of the b-wave amplitude of the ERG in the water group. Retinal structure and function were preserved in supplemented animals. Supplement induced a significant increase in omega-3 fatty acids in plasma by 168% for eicosapentaenoic acid (EPA), 142% for docosapentaenoic acid (DPA) and 19% for docosahexaenoic acid (DHA) and a decrease in the omega-6 fatty acids, DPA by 28%. In the retina, supplement induced significant reduction of linolenic acid by 67% and an increase in EPA and DPA by 80% and 72%, respectively, associated with significant decrease in omega-6 DPA by 42%. Supplement did not affect rhodopsin content or rod-response recovery. The present data indicate that supplement rapidly modified the fatty acid content and induced an accumulation of EPA in the retina without affecting rhodopsin content or recovery. In addition, it protected the retina from oxidative stress induced by light. Therefore, this supplement might be beneficial to slow down progression of certain retinal degeneration. PMID:26042773

Phylogenetic relationships of the endangered Shenandoah salamander (Plethodon shenandoah) and other salamanders of the Plethodon cinereus group (Caudata : Plethodontidae)

USGS Publications Warehouse

Sites, J.W.; Morando, M.; Highton, R.; Huber, F.; Jung, R.E.

2004-01-01

The Shenandoah salamander (Plethodon shenandoah), known from isolated talus slopes on three of the highest mountains in Shenandoah National Park, is listed as state-endangered in Virginia and federally endangered under the U.S. Endangered Species Act. A 1999 paper by G. R. Thurow described P. shenandoah-like salamanders from three localities further south in the Blue Ridge Physiographic Province, which, if confirmed, would represent a range extension for P. shenandoah of approximately 90 km from its nearest known locality. Samples collected from two of these three localities were included in a molecular phylogenetic study of the known populations of P. shenandoah, and all other recognized species in the Plethodon cinereus group, using a 792 bp region of the mitochondrial cytochrome-b gene. Phylogenetic estimates were based on Bayesian, maximum likelihood, and maximum parsimony methods and topologies examined for placement of the new P. shenandoah-like samples relative to all others. All topologies recovered all haplotypes of the P. shenandoah-like animals nested within P. cinereus, and a statistical comparison of the best likelihood tree topology with one with an enforced (Thurow + Shenandoah P. shenandoah) clade revealed that the unconstrained tree had a significantly lower -In L score (P < 0.05, using the Shimodaira-Hasegawa test) than the constraint tree. This result and other anecdotal information give us no solid reason to consider the Thurow report valid. The current recovery program for P. shenandoah should remain focused on populations in Shenandoah National Park.

Evidence of a new niche for a North American salamander: Aneides vagrans residing in the canopy of old-growth redwood forest

Treesearch

James C. Spickler; Stephen C. Sillett; Sharyn B. Marks; Hartwell H. Welsh Jr.

2006-01-01

We investigated habitat use and movements of the wandering salamander, Aneides vagrans, in an old-growth forest canopy. We conducted a mark-recapture study of salamanders in the crowns of five large redwoods (Sequoia sempervirens) in Prairie Creek Redwoods State Park, California. This represented a first attempt to document the...

Delayed rectifier K channels contribute to contrast adaptation in mammalian retinal ganglion cells

PubMed Central

Weick, Michael; Demb, Jonathan B.

2011-01-01

SUMMARY Retinal ganglion cells adapt by reducing their sensitivity during periods of high contrast. Contrast adaptation in the firing response depends on both presynaptic and intrinsic mechanisms. Here, we investigated intrinsic mechanisms for contrast adaptation in OFF Alpha ganglion cells in the in vitro guinea pig retina. Using either visual stimulation or current injection, we show that brief depolarization evoked spiking and suppressed firing during subsequent depolarization. The suppression could be explained by Na channel inactivation, as shown in salamander cells. However, brief hyperpolarization in the physiological range (5–10 mV) also suppressed firing during subsequent depolarization. This suppression was sensitive selectively to blockers of delayed-rectifier K channels (KDR). Somatic membrane patches showed TEA-sensitive KDR currents with activation near −25 mV and removal of inactivation at voltages negative to Vrest. Brief periods of hyperpolarization apparently remove KDR inactivation and thereby increase the channel pool available to suppress excitability during subsequent depolarization. PMID:21745646

Retinitis Pigmentosa

MedlinePlus

... Action You are here Home › Retinal Diseases Listen Retinitis Pigmentosa What is retinitis pigmentosa? What are the symptoms? ... is available? What treatment is available? What is retinitis pigmentosa? Retinitis pigmentosa, also known as RP, refers to ...

Phenotypic spectrum of autosomal recessive cone-rod dystrophies caused by mutations in the ABCA4 (ABCR) gene.

PubMed

Klevering, B Jeroen; Blankenagel, Anita; Maugeri, Alessandra; Cremers, Frans P M; Hoyng, Carel B; Rohrschneider, Klaus

2002-06-01

To describe the phenotype of 12 patients with autosomal recessive or isolated cone-rod types of progressive retinal degeneration (CRD) caused by mutations in the ABCA4 gene. The charts of patients who had originally received a diagnosis of isolated or autosomal recessive CRD were reviewed after molecular analysis revealed mutations in the ABCA4 gene. In two of the patients both the photopic and scotopic electroretinogram were nonrecordable. In the remainder, the photopic cone b-wave amplitudes appeared to be more seriously affected than the scotopic rod b-wave amplitudes. Although the clinical presentation was heterogeneous, all patients experienced visual loss early in life, impaired color vision, and a central scotoma. Fundoscopy revealed evidence of early-onset maculopathy, sometimes accompanied by involvement of the retinal periphery in the later stages of the disease. Mutations in the ABCA4 gene are the pathologic cause of the CRD-like dystrophy in these patients, and the resultant clinical pictures are complex and heterogeneous. Given this wide clinical spectrum of CRD-like phenotypes associated with ABCA4 mutations, detailed clinical subclassifications are difficult and may not be very useful.

Protective effect of high concentration of BN52021 on retinal contusion in cat eyes.

PubMed

Huang, Jin-Feng; Zhao, Hai-Peng; Yang, Yan-Feng; Huang, Hui-Min; Yao, Yi; Wang, Zhi-Jun

2015-05-09

Blunt injuries/contusion on eyes might cause retina blunt trauma. This study is to evaluate the protective function of BN52021 against retinal trauma. A total of 70 cats, 6 months old, were divided into six groups: Group A to E (n = 12) and normal control (N) group (n = 10). The right eyes in Group A to E were contused. All experiments were performed under general anesthetization. Retrobulbar injections of medication in right eyes were performed. Cats were administrated with 0.5 mL of normal saline (NS), dimethyl sulphoxide, 0.2 g/L BN52021, 1 g/L BN52021 and 5 g/L BN52021, respectively. Cats in Group N were administrated with 0.5 mL of NS. Intraocular pressure (IOP), flash electroretinogram (ERG), and retinal nerve fiber layer (RNFL) thickness were measured. Hematoxylin and eosin (HE) staining and transmission electron microscope (TEM) were detected. No significant difference was observed in IOP levels among groups. Comparing with cats in Group N, those in Group A to E showed significant lower amplitudes of rod a- and b-waves (P < 0.05). Amplitudes of rod a- and b-waves were increased by administration of high concentration of BN52021 (≥ 1 g/L). Moreover, high concentration of BN52021 decreased the RNFL thickness increased by contusion. Axons in RNFL in Group E arranged neatly at 7 days after modeling. The degenerated axons caused by contusion were repaired by BN52021. The administration of high concentration of (≥ 1 g/L) BN52021 could partially repair retinal function in contused cat eyes.

Survey for the pathogenic chytrid fungus Batrachochytrium dendrobatidis in southwestern North Carolina salamander populations.

PubMed

Keitzer, S Conor; Goforth, Reuben; Pessier, Allan P; Johnson, April J

2011-04-01

Batrachochytrium dendrobatidis is a fungal pathogen responsible for a potentially fatal disease of amphibians. We conducted a survey for B. dendrobatidis in the Appalachian Mountains of southwestern North Carolina, USA, from 10 June to 23 July 23 2009. Ventral skin swabs were collected from plethodontid salamanders (n=278) and real-time PCR was performed to test for the presence of B. dendrobatidis. We found no evidence of B. dendrobatidis, suggesting that B. dendrobatidis is absent or present in such low levels that it was undetected. If B. dendrobatidis was present at the time of our sampling, this survey supports evidence of low prevalence of B. dendrobatidis in North American headwater stream salamander populations.

Partial preservation of rod and cone ERG function following subretinal injection of ARPE-19 cells in RCS rats.

PubMed

Sauvé, Y; Pinilla, I; Lund, R D

2006-04-01

We quantified rod- and cone-related electroretinogram (ERG) responses following subretinal injections of the human-derived retinal pigment epithelial (hRPE) cell line ARPE-19 at age P23 to prevent progressive photoreceptor loss in the Royal College of Surgeons (RCS) rat. Culture medium-injected eyes served as sham controls. At P60, in comparison with sham-injected eyes, all recordings from hRPE-injected eyes showed preserved scotopic a- and b-waves, oscillatory potentials, double-flash-derived rod b-waves and photopic cone b-waves, and flicker critical fusion frequencies and amplitudes. Although the actual preservation did not exceed 10% of a-wave and 20% of b-wave amplitude values in non-dystrophic RCS and deteriorated rapidly by P90, rod- and cone-related ERG parameters were still recordable up to P120 unlike the virtually unresponsive sham-injected eyes.

Physical condition, sex, and age-class of eastern red-backed salamanders (Plethodon cinereus) in forested and open habitats of West Virginia, USA

Treesearch

Breanna L. Riedel; Kevin R. Russell; W. Mark Ford

2012-01-01

Nonforested habitats such as open fields and pastures have been considered unsuitable for desiccation-prone woodland salamanders such as the Eastern Red-backed Salamander (Plethodon cinereus). Recent research has suggested that Plethodon cinereus may not only disperse across but also reside within open habitats including fields,...

Outer Retinal Tubulation in Degenerative Retinal Disorders

PubMed Central

Goldberg, Naomi R.; Greenberg, Jonathan P.; Laud, Ketan; Tsang, Stephen; Freund, K. Bailey

2013-01-01

Objective To demonstrate outer retinal tubulation (ORT) in various degenerative retinal disorders. Methods This was a retrospective review of the multimodal imaging of 29 eyes of 15 patients with various retinal dystrophies and inflammatory maculopathies manifesting ORT. The morphologic features of ORT and its evolution over time were analyzed using spectral-domain optical coherence tomography (SD-OCT) data. Results Outer retinal tubulation was identified as round or ovoid structures with hyper-reflective borders in pattern dystrophy (6 eyes), acute zonal occult outer retinopathy (5 eyes), retinitis pigmentosa (4 eyes), Stargardt disease (4 eyes), gyrate atrophy (2 eyes), choroideremia (2 eyes), and various other degenerative conditions. These structures appeared to develop from the invagination of photoreceptors at the junction of intact and atrophic outer retina. During follow-up, the number and distribution of ORT largely remained stable. As zones of atrophy enlarged, the frequency of ORT appeared to increase. The ORT structures were found in fewer than 10% of patients with retinitis pigmentosa, Stargardt, or pattern dystrophy. Conclusion Outer retinal tubulation is found in various degenerative retinal disorders that share in common damage to the outer retina and/or retinal pigment epithelium. The presence of ORT may be in an indicator of underlying disease stage and severity. PMID:23676993

Determining consequences of retinal membrane guanylyl cyclase (RetGC1) deficiency in human Leber congenital amaurosis en route to therapy: residual cone-photoreceptor vision correlates with biochemical properties of the mutants

PubMed Central

Jacobson, Samuel G.; Cideciyan, Artur V.; Peshenko, Igor V.; Sumaroka, Alexander; Olshevskaya, Elena V.; Cao, Lihui; Schwartz, Sharon B.; Roman, Alejandro J.; Olivares, Melani B.; Sadigh, Sam; Yau, King-Wai; Heon, Elise; Stone, Edwin M.; Dizhoor, Alexander M.

2013-01-01

The GUCY2D gene encodes retinal membrane guanylyl cyclase (RetGC1), a key component of the phototransduction machinery in photoreceptors. Mutations in GUCY2D cause Leber congenital amaurosis type 1 (LCA1), an autosomal recessive human retinal blinding disease. The effects of RetGC1 deficiency on human rod and cone photoreceptor structure and function are currently unknown. To move LCA1 closer to clinical trials, we characterized a cohort of patients (ages 6 months—37 years) with GUCY2D mutations. In vivo analyses of retinal architecture indicated intact rod photoreceptors in all patients but abnormalities in foveal cones. By functional phenotype, there were patients with and those without detectable cone vision. Rod vision could be retained and did not correlate with the extent of cone vision or age. In patients without cone vision, rod vision functioned unsaturated under bright ambient illumination. In vitro analyses of the mutant alleles showed that in addition to the major truncation of the essential catalytic domain in RetGC1, some missense mutations in LCA1 patients result in a severe loss of function by inactivating its catalytic activity and/or ability to interact with the activator proteins, GCAPs. The differences in rod sensitivities among patients were not explained by the biochemical properties of the mutants. However, the RetGC1 mutant alleles with remaining biochemical activity in vitro were associated with retained cone vision in vivo. We postulate a relationship between the level of RetGC1 activity and the degree of cone vision abnormality, and argue for cone function being the efficacy outcome in clinical trials of gene augmentation therapy in LCA1. PMID:23035049

A study of the human rod and cone electroretinogram a-wave component

NASA Astrophysics Data System (ADS)

Barraco, R.; Persano Adorno, D.; Bellomonte, L.; Brai, M.

2009-03-01

The study of the electrical response of the retina to a luminous stimulus is one of the main fields of research in ocular electrophysiology. The features of the first component (a-wave) of the retinal response reflect the functional integrity of the two populations of photoreceptors: rods and cones. We fit the a-wave for pathological subjects with functions that account for possible mechanisms governing the kinetics of the photoreceptors. The paper extends a previous analysis, carried out for normal subjects, in which both populations are active, to patients affected by two particular diseases that reduce the working populations to only one. The pathologies investigated are Achromatopsia, a cone disease, and Congenital Stationary Night Blindness, a rod problem. We present evidence that the analysis of a pathological a-wave can be employed to quantitatively measure either cone or rod activities and to test hypotheses about their responses. The results show that the photoreceptoral responses differ in the two cases and functions implying a different number of photocascade stages are necessary to achieve a correct modeling of the early phototransduction process. Numerical values of the parameters characterizing the best-fit functions are given and discussed.

Rapid degeneration of rod photoreceptors expressing self-association-deficient arrestin-1 mutant

PubMed Central

Song, Xiufeng; Seo, Jungwon; Baameur, Faiza; Vishnivetskiy, Sergey A.; Chen, Qiuyan; Kook, Seunghyi; Kim, Miyeon; Brooks, Evan K.; Altenbach, Christian; Hong, Yuan; Hanson, Susan M.; Palazzo, Maria C.; Chen, Jeannie; Hubbell, Wayne L.; Gurevich, Eugenia V.; Gurevich, Vsevolod V.

2013-01-01

Arrestin-1 binds light-activated phosphorhodopsin and ensures timely signal shutoff. We show that high transgenic expression of an arrestin-1 mutant with enhanced rhodopsin binding and impaired oligomerization causes apoptotic rod death in mice. Dark rearing does not prevent mutant-induced cell death, ruling out the role of arrestin complexes with light-activated rhodopsin. Similar expression of WT arrestin-1 that robustly oligomerizes, which leads to only modest increase in the monomer concentration, does not affect rod survival. Moreover, WT arrestin-1 co-expressed with the mutant delays retinal degeneration. Thus, arrestin-1 mutant directly affects cell survival via binding partner(s) other than light-activated rhodopsin. Due to impaired self-association of the mutant its high expression dramatically increases the concentration of the monomer. The data suggest that monomeric arrestin-1 is cytotoxic and WT arrestin-1 protects rods by forming mixed oligomers with the mutant and/or competing with it for the binding to non-receptor partners. Thus, arrestin-1 self-association likely serves to keep low concentration of the toxic monomer. The reduction of the concentration of harmful monomer is an earlier unappreciated biological function of protein oligomerization. PMID:24012956

Rapid degeneration of rod photoreceptors expressing self-association-deficient arrestin-1 mutant.

PubMed

Song, Xiufeng; Seo, Jungwon; Baameur, Faiza; Vishnivetskiy, Sergey A; Chen, Qiuyan; Kook, Seunghyi; Kim, Miyeon; Brooks, Evan K; Altenbach, Christian; Hong, Yuan; Hanson, Susan M; Palazzo, Maria C; Chen, Jeannie; Hubbell, Wayne L; Gurevich, Eugenia V; Gurevich, Vsevolod V

2013-12-01

Arrestin-1 binds light-activated phosphorhodopsin and ensures timely signal shutoff. We show that high transgenic expression of an arrestin-1 mutant with enhanced rhodopsin binding and impaired oligomerization causes apoptotic rod death in mice. Dark rearing does not prevent mutant-induced cell death, ruling out the role of arrestin complexes with light-activated rhodopsin. Similar expression of WT arrestin-1 that robustly oligomerizes, which leads to only modest increase in the monomer concentration, does not affect rod survival. Moreover, WT arrestin-1 co-expressed with the mutant delays retinal degeneration. Thus, arrestin-1 mutant directly affects cell survival via binding partner(s) other than light-activated rhodopsin. Due to impaired self-association of the mutant its high expression dramatically increases the concentration of the monomer. The data suggest that monomeric arrestin-1 is cytotoxic and WT arrestin-1 protects rods by forming mixed oligomers with the mutant and/or competing with it for the binding to non-receptor partners. Thus, arrestin-1 self-association likely serves to keep low concentration of the toxic monomer. The reduction of the concentration of harmful monomer is an earlier unappreciated biological function of protein oligomerization. © 2013.

Modeling Photo-Bleaching Kinetics to Create High Resolution Maps of Rod Rhodopsin in the Human Retina

PubMed Central

Ehler, Martin; Dobrosotskaya, Julia; Cunningham, Denise; Wong, Wai T.; Chew, Emily Y.; Czaja, Wojtek; Bonner, Robert F.

2015-01-01

We introduce and describe a novel non-invasive in-vivo method for mapping local rod rhodopsin distribution in the human retina over a 30-degree field. Our approach is based on analyzing the brightening of detected lipofuscin autofluorescence within small pixel clusters in registered imaging sequences taken with a commercial 488nm confocal scanning laser ophthalmoscope (cSLO) over a 1 minute period. We modeled the kinetics of rhodopsin bleaching by applying variational optimization techniques from applied mathematics. The physical model and the numerical analysis with its implementation are outlined in detail. This new technique enables the creation of spatial maps of the retinal rhodopsin and retinal pigment epithelium (RPE) bisretinoid distribution with an ≈ 50μm resolution. PMID:26196397

Protection against methanol-induced retinal toxicity by LED photostimulation

NASA Astrophysics Data System (ADS)

Whelan, Harry T.; Wong-Riley, Margaret T. T.; Eells, Janis T.

2002-06-01

We have initiated experiments designed to test the hypothesis that 670-nm Light-Emitting Diode (LED) exposure will attenuate formate-induced retinal dysfunction in a rodent model of methanol toxicity. Methanol intoxication produces toxic injury to the retina. The toxic metabolite formed in methanol intoxication is formic acid, a mitochondrial toxin known to inhibit cytochrome oxidase activity. 670-nm LED light has been hypothesized to act by stimulating cytochrome oxidase activity. To test this hypothesis, one group of animals was intoxicated with methanol, a second group was intoxicated with methanol and LED-treated and a third group was untreated. LED treatment (670 nm for 1 min 45 seconds equals 50 mW/cm2, 4 joules/cm2) was administered at 5, 25, and 50 hours after the initial dose of methanol. At 72 hours of methanol intoxication, retinal function was assessed by measurement of ERG responses and retinas were prepared for histologic analysis. ERG responses recorded in methanol-intoxicated animals revealed profound attenuation of both rod-dominated and UV-cone mediated responses. In contrast, methanol- intoxicated animals exposed to LED treatment exhibited a nearly complete recovery of rod-dominated ERG responses and a slight improvement of UV-cone mediated ERG responses. LED treatment also protected the retina against the histopathologic changes produced by formate in methanol intoxication. These data provide evidence that LED phototherapy protects the retina against the cytotoxic actions of formate and are consistent with the hypothesis that LED photostimulation improves mitochondrial respiratory chain function.

Quantification of Retinogenesis in 3D Cultures Reveals Epigenetic Memory and Higher Efficiency in iPSCs Derived from Rod Photoreceptors.

PubMed

Hiler, Daniel; Chen, Xiang; Hazen, Jennifer; Kupriyanov, Sergey; Carroll, Patrick A; Qu, Chunxu; Xu, Beisi; Johnson, Dianna; Griffiths, Lyra; Frase, Sharon; Rodriguez, Alberto R; Martin, Greg; Zhang, Jiakun; Jeon, Jongrye; Fan, Yiping; Finkelstein, David; Eisenman, Robert N; Baldwin, Kristin; Dyer, Michael A

2015-07-02

Cell-based therapies to treat retinal degeneration are now being tested in clinical trials. However, it is not known whether the source of stem cells is important for the production of differentiated cells suitable for transplantation. To test this, we generated induced pluripotent stem cells (iPSCs) from murine rod photoreceptors (r-iPSCs) and scored their ability to make retinae by using a standardized quantitative protocol called STEM-RET. We discovered that r-iPSCs more efficiently produced differentiated retinae than did embryonic stem cells (ESCs) or fibroblast-derived iPSCs (f-iPSCs). Retinae derived from f-iPSCs had fewer amacrine cells and other inner nuclear layer cells. Integrated epigenetic analysis showed that DNA methylation contributes to the defects in f-iPSC retinogenesis and that rod-specific CTCF insulator protein-binding sites may promote r-iPSC retinogenesis. Together, our data suggest that the source of stem cells is important for producing retinal neurons in three-dimensional (3D) organ cultures. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterization of spontaneous excitatory synaptic currents in salamander retinal ganglion cells.

PubMed Central

Taylor, W R; Chen, E; Copenhagen, D R

1995-01-01

1. Spontaneous excitatory postsynaptic currents (sEPSCs) were recorded under voltage-clamp conditions. Consistent with activation of non-NMDA-type glutamate receptors, the sEPSCs reversed at potentials above 0 mV, were blocked by 1 microM CNQX and prolonged by 2 mM aniracetam. 2. The peak conductance of the averaged sEPSCs (n = 70-400) was 130 +/- 60 pS (mean +/- S.D.; 17 cells, ranging from 70 to 290 pS). Amplitude distributions were skewed towards larger amplitudes. 3. The decay of individual and mean sEPSCs was exponential with a mean time constant (tau d) of 3.75 +/- 0.84 ms (n = 13), which was voltage independent. The 10-90% rise time of the sEPSCs was 1.30 +/- 0.44 ms (n = 13). There was no correlation between sEPSC rise time and tau d suggesting that dendritic filtering alone did not shape the time course of sEPSCs. 4. Light-evoked EPSCs in these retinal ganglion cells are mediated by concomitant activation of NMDA and non-NMDA receptors; however, no NMDA component was discerned in the sEPSCs, even when recording at -96 mV in Mg(2+)-free solutions. The decay time course was not altered by 20 microM AP7, an NMDA antagonist, nor was an NMDA component unmasked by adding glycine or D-serine. These results suggest that NMDA and non-NMDA receptors are not coactivated by a single vesicle of transmitter during spontaneous release, and thus are probably not colocalized in the postsynaptic membrane at the sites of spontaneous release. 5. The sEPSCs were an order of magnitude faster than the non-NMDA receptor-mediated EPSCs evoked by light stimuli, and it is proposed that the EPSC time course is determined largely by the extended time course of release of synaptic vesicles from bipolar cells. The quantal content of a light-evoked non-NMDA receptor-mediated EPSC in an on-off cell is about 200 quanta. Images Figure 6 PMID:7562636

[Preliminary analysis of retinal gene expression profile of diabetic rat].

PubMed

Mei, Yan; Zhou, Hong-ying; Xiang, Tao; Lu, You-guang; Li, Ai-dong; Tang, En-jie; Yang, Hui-jun

2005-10-01

Establishing the retinal gene expression profiles of non-diabetic rat and diabetic rat and comparing the profiles in order to analyze the possible genes related with diabetic retinopathy. The whole retinal transcriptional fragments of non-diabetic rat and 8-week diabetic rat were obtained by restriction fragments differential display-PCR (RFDD-PCR). Bioinformatic analysis of retinal gene expression was performed using soft wares, including Fragment Analysis. After comparison of the expression profiles, the related gene fragments of diabetic retinopathy were initially selected as the target gene of further approach. A total of 3639 significant fragments were obtained. By means of more than 3-fold contrast of fluorescent intensity as the differential expression standard, the authors got 840 differential fragments, accounting for 23.08% of the expressed numbers and including 5 visual related genes, 13 excitatory neruotransmitter genes and 3 inhibitory neurotransmitter genes. At the 8th week, the expression of Rhodopsin kinase, beta-arrestin, Phosducinìrod photoreceptor cGMP-gated channel and Rpe65 as well as iGlu R1-4 were down-regulated. mGluRs and GABA-Rs were all up-regulated, whereas the expression of GlyR was unchanged. These results prompt again that the changes in retinal nervous layer of rat have occurred at an early stage of diabetes. The genes expression pattern of visual related genes and excitatory and inhibitory neurotransmitters in rat diabetic retina have been involved in neuro-dysfunctions of diabetic retina.

Near infrared reflectance spectroscopy studies of Chinese giant salamanders in aquaculture production

USDA-ARS?s Scientific Manuscript database

NIR spectra were collected at three surface locations for Chinese giant salamanders to ascertain whether spectral signatures could be separated by anatomical, presumably physiologically-based, locations. The first location was the smooth area immediately above the cloaca on the animal’s abdomen, whi...

Woodland salamander response to two prescribed fires in the central Appalachians

Treesearch

W. Mark Ford; Jane L. Rodrigue; Ella L. Rowan; Steven B. Castleberry; Thomas M. Schuler

2010-01-01

Using coverboard arrays, we monitored woodland salamanders on the Fernow Experimental Forest in the central Appalachian Mountains, West Virginia, USA prior to and following two prescribed fires in mixed oak (Quercus spp.) forest stands. Treatments were burn plots on upper slopes or lower slopes fenced to prevent white-tailed deer (Odocoileus...

Light adaptation alters the source of inhibition to the mouse retinal OFF pathway

PubMed Central

Mazade, Reece E.

2013-01-01

Sensory systems must avoid saturation to encode a wide range of stimulus intensities. One way the retina accomplishes this is by using both dim-light-sensing rod and bright-light-sensing cone photoreceptor circuits. OFF cone bipolar cells are a key point in this process, as they receive both excitatory input from cones and inhibitory input from AII amacrine cells via the rod pathway. However, in addition to AII amacrine cell input, other inhibitory inputs from cone pathways also modulate OFF cone bipolar cell light signals. It is unknown how these inhibitory inputs to OFF cone bipolar cells change when switching between rod and cone pathways or whether all OFF cone bipolar cells receive rod pathway input. We found that one group of OFF cone bipolar cells (types 1, 2, and 4) receive rod-mediated inhibitory inputs that likely come from the rod-AII amacrine cell pathway, while another group of OFF cone bipolar cells (type 3) do not. In both cases, dark-adapted rod-dominant light responses showed a significant contribution of glycinergic inhibition, which decreased with light adaptation and was, surprisingly, compensated by an increase in GABAergic inhibition. As GABAergic input has distinct timing and spatial spread from glycinergic input, a shift from glycinergic to GABAergic inhibition could significantly alter OFF cone bipolar cell signaling to downstream OFF ganglion cells. Larger GABAergic input could reflect an adjustment of OFF bipolar cell spatial inhibition, which may be one mechanism that contributes to retinal spatial sensitivity in the light. PMID:23926034

Embryo Development inside Female Salamander (Ambystoma jeffersonianum-laterale) Prior to Egg Laying

PubMed Central

Charney, Noah D.; Castorino, John J.; Dobro, Megan J.; Steely, Sarah L.

2014-01-01

The length of embryo retention prior to oviposition is a critical evolutionary trait. In all oviparous salamanders, which include the vast majority of species in the order, fertilization is thought to occur at the time of egg laying. Embryos then enter the first cleavage stage several hours after being deposited. This pattern holds for previously studied individuals in the Ambystoma jeffersonianum-laterale complex. Here, we document an instance in which a female Ambystoma jeffersonianum-laterale was carrying embryos internally that had already reached stage 10 of development. Development likely began several days prior to the start of migration to the breeding pond. This is the first such record for any egg-laying salamander, and suggests a degree of plasticity in the timing of fertilization and development not previously recognized. Further work is needed to ascertain the prevalence, mechanics, and evolutionary significance of this phenomenon. PMID:24651275

Advances in repairing the degenerate retina by rod photoreceptor transplantation.

PubMed

Pearson, Rachael A

2014-01-01

Despite very different aetiologies, age-related macular degeneration (AMD) and most inherited retinal disorders culminate in the same final common pathway, loss of the light-sensitive photoreceptors. There are few clinical treatments and none can reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. The past decade has seen a number of landmark achievements in this field, which together provide strong justification for continuing investigation into photoreceptor replacement strategies. These include proof of principle for restoring vision by rod-photoreceptor transplantation in mice with congenital stationary night blindness and advances in stem cell biology, which have led to the generation of complete optic structures in vitro from embryonic stem cells. The latter represents enormous potential for generating suitable and renewable donor cells with which to achieve the former. However, there are still challenges presented by the degenerating recipient retinal environment that must be addressed as we move to translating these technologies towards clinical application. Copyright © 2014 The Author. Published by Elsevier Inc. All rights reserved.

Conservation genetics of extremely isolated urban populations of the northern dusky salamander (Desmognathus fuscus) in New York City

PubMed Central

Zak, Yana; Pehek, Ellen

2013-01-01

Urbanization is a major cause of amphibian decline. Stream-dwelling plethodontid salamanders are particularly susceptible to urbanization due to declining water quality and hydrological changes, but few studies have examined these taxa in cities. The northern dusky salamander (Desmognathus fuscus) was once common in the New York City metropolitan area, but has substantially declined throughout the region in recent decades. We used five tetranucleotide microsatellite loci to examine population differentiation, genetic variation, and bottlenecks among five remnant urban populations of dusky salamanders in NYC. These genetic measures provide information on isolation, prevalence of inbreeding, long-term prospects for population persistence, and potential for evolutionary responses to future environmental change. All populations were genetically differentiated from each other, and the most isolated populations in Manhattan have maintained very little genetic variation (i.e. <20% heterozygosity). A majority of the populations also exhibited evidence of genetic bottlenecks. These findings contrast with published estimates of high genetic variation within and lack of structure between populations of other desmognathine salamanders sampled over similar or larger spatial scales. Declines in genetic variation likely resulted from population extirpations and the degradation of stream and terrestrial paths for dispersal in NYC. Loss of genetic variability in populations isolated by human development may be an underappreciated cause and/or consequence of the decline of this species in urbanized areas of the northeast USA. PMID:23646283

SPATIALLY AUTOCORRELATED DEMOGRAPHY AND INTERPOND MIGRATION IN THE CALIFORNIA TIGER SALAMANDER (AMBYSTOME CALIFORNIENSE)

EPA Science Inventory

We investigated the metapopulation structure of the California tiger salamander (Ambystoma californiense) using a combination of indirect and direct methods to evaluate two key requirements of modern metapopulation models: 1) that patches support somewhat independent populations ...

Dark Light, Rod Saturation, and the Absolute and Incremental Sensitivity of Mouse Cone Vision

PubMed Central

Naarendorp, Frank; Esdaille, Tricia M.; Banden, Serenity M.; Andrews-Labenski, John; Gross, Owen P.; Pugh, Edward N.

2012-01-01

Visual thresholds of mice for the detection of small, brief targets were measured with a novel behavioral methodology in the dark and in the presence of adapting lights spanning ∼8 log10 units of intensity. To help dissect the contributions of rod and cone pathways, both wild-type mice and mice lacking rod (Gnat1−/−) or cone (Gnat2cpfl3) function were studied. Overall, the visual sensitivity of mice was found to be remarkably similar to that of the human peripheral retina. Rod absolute threshold corresponded to 12-15 isomerized pigment molecules (R*) in image fields of 800 to 3000 rods. Rod “dark light” (intrinsic retinal noise in darkness) corresponded to that estimated previously from single-cell recordings, 0.012R*s−1rod−1, indicating that spontaneous thermalisomerizations are responsible. Psychophysical rod saturation was measured for the first time in a nonhman species and found to be very similar to that of the human rod monochromat. Cone threshold corresponded to ∼5 R* cone−1 in an image field of 280 cones. Cone dark light was equivalent to ∼5000 R*s−1 cone−1, consistent with primate single-cell data but 100-fold higher than predicted by recent measurements of the rate of thermal isomerization of mouse cone opsins, indicating that nonopsin sources of noise determine cone threshold. The new, fully automated behavioral method is based on the ability of mice to learn to interrupt spontaneous wheel running on the presentation of a visual cue and provides an efficient and highly reliable means of examining visual function in naturally behaving normal and mutant mice. PMID:20844144

Macular Pigment and Lutein Supplementation in ABCA4-associated Retinal Degenerations

PubMed Central

Aleman, Tomas S.; Cideciyan, Artur V.; Windsor, Elizabeth A. M.; Schwartz, Sharon B.; Swider, Malgorzata; Chico, John D.; Sumaroka, Alexander; Pantelyat, Alexander Y.; Duncan, Keith G.; Gardner, Leigh M.; Emmons, Jessica M.; Steinberg, Janet D.; Stone, Edwin M.; Jacobson, Samuel G.

2008-01-01

PURPOSE To determine macular pigment (MP) optical density (OD) in patients with ABCA4-associated retinal degenerations (ABCA4-RD) and the response of MP and vision to supplementation with lutein. METHODS Stargardt disease or cone-rod dystrophy patients with foveal fixation and with known or suspected disease-causing mutations in the ABCA4 gene were included. MPOD profiles were measured with heterochromatic flicker photometry. Serum carotenoids, visual acuity, foveal sensitivity and retinal thickness were quantified. Changes in MPOD and central vision were determined in a subset of patients receiving oral supplementation with lutein for 6 months. RESULTS MPOD in patients ranged from normal to markedly abnormal. As a group, ABCA4-RD patients had reduced foveal MPOD and there was strong correlation with retinal thickness. Average foveal tissue concentration of MP, estimated by dividing MPOD by retinal thickness, was normal in patients whereas serum concentration of lutein and zeaxanthin was significantly lower than normal. After oral lutein supplementation for 6 months, 91% of the patients showed significant increases in serum lutein and 63% of the patient eyes showed a significant augmentation in MPOD. The retinal responders tended to be female, and have lower serum lutein and zeaxanthin, lower MPOD and greater retinal thickness at baseline. Responding eyes had significantly lower baseline MP concentration compared to non-responding eyes. Central vision was unchanged after the period of supplementation. CONCLUSIONS MP is strongly affected by the stage of ABCA4 disease leading to abnormal foveal architecture. MP could be augmented by supplemental lutein in some patients. There was no change in central vision after 6 months of lutein supplementation. Long-term influences on the natural history of this supplement on macular degenerations require further study. PMID:17325179

Morphological Diversity of the Rod Spherule: A Study of Serially Reconstructed Electron Micrographs

PubMed Central

Li, Shuai; Mitchell, Joe; Briggs, Deidrie J.; Young, Jaime K.; Long, Samuel S.; Fuerst, Peter G.

2016-01-01

Purpose Rod spherules are the site of the first synaptic contact in the retina’s rod pathway, linking rods to horizontal and bipolar cells. Rod spherules have been described and characterized through electron micrograph (EM) and other studies, but their morphological diversity related to retinal circuitry and their intracellular structures have not been quantified. Most rod spherules are connected to their soma by an axon, but spherules of rods on the surface of the Mus musculus outer plexiform layer often lack an axon and have a spherule structure that is morphologically distinct from rod spherules connected to their soma by an axon. Retraction of the rod axon and spherule is often observed in disease processes and aging, and the retracted rod spherule superficially resembles rod spherules lacking an axon. We hypothesized that retracted spherules take on an axonless spherule morphology, which may be easier to maintain in a diseased state. To test our hypothesis, we quantified the spatial organization and subcellular structures of rod spherules with and without axons. We then compared them to the retracted spherules in a disease model, mice that overexpress Dscam (Down syndrome cell adhesion molecule), to gain a better understanding of the rod synapse in health and disease. Methods We reconstructed serial EM images of wild type and DscamGoF (gain of function) rod spherules at a resolution of 7 nm in the X-Y axis and 60 nm in the Z axis. Rod spherules with and without axons, and retracted spherules in the DscamGoF retina, were reconstructed. The rod spherule intracellular organelles, the invaginating dendrites of rod bipolar cells and horizontal cell axon tips were also reconstructed for statistical analysis. Results Stereotypical rod (R1) spherules occupy the outer two-thirds of the outer plexiform layer (OPL), where they present as spherical terminals with large mitochondria. This spherule group is highly uniform and composed more than 90% of the rod spherule

Morphological Diversity of the Rod Spherule: A Study of Serially Reconstructed Electron Micrographs.

PubMed

Li, Shuai; Mitchell, Joe; Briggs, Deidrie J; Young, Jaime K; Long, Samuel S; Fuerst, Peter G

2016-01-01

Rod spherules are the site of the first synaptic contact in the retina's rod pathway, linking rods to horizontal and bipolar cells. Rod spherules have been described and characterized through electron micrograph (EM) and other studies, but their morphological diversity related to retinal circuitry and their intracellular structures have not been quantified. Most rod spherules are connected to their soma by an axon, but spherules of rods on the surface of the Mus musculus outer plexiform layer often lack an axon and have a spherule structure that is morphologically distinct from rod spherules connected to their soma by an axon. Retraction of the rod axon and spherule is often observed in disease processes and aging, and the retracted rod spherule superficially resembles rod spherules lacking an axon. We hypothesized that retracted spherules take on an axonless spherule morphology, which may be easier to maintain in a diseased state. To test our hypothesis, we quantified the spatial organization and subcellular structures of rod spherules with and without axons. We then compared them to the retracted spherules in a disease model, mice that overexpress Dscam (Down syndrome cell adhesion molecule), to gain a better understanding of the rod synapse in health and disease. We reconstructed serial EM images of wild type and DscamGoF (gain of function) rod spherules at a resolution of 7 nm in the X-Y axis and 60 nm in the Z axis. Rod spherules with and without axons, and retracted spherules in the DscamGoF retina, were reconstructed. The rod spherule intracellular organelles, the invaginating dendrites of rod bipolar cells and horizontal cell axon tips were also reconstructed for statistical analysis. Stereotypical rod (R1) spherules occupy the outer two-thirds of the outer plexiform layer (OPL), where they present as spherical terminals with large mitochondria. This spherule group is highly uniform and composed more than 90% of the rod spherule population. Rod spherules

Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

PubMed

Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

2016-08-10

We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids. 2016 BMJ Publishing Group Ltd.

Extracellular H+ fluxes from tiger salamander Müller (glial) cells measured using self-referencing H+-selective microelectrodes.

PubMed

Kreitzer, Matthew A; Swygart, David; Osborn, Meredith; Skinner, Blair; Heer, Chad; Kaufman, Ryan; Williams, Bethany; Shepherd, Lexi; Caringal, Hannah; Gongwer, Michael; Tchernookova, Boriana K; Malchow, Robert P

2017-12-01

Self-referencing H + -selective electrodes were used to measure extracellular H + fluxes from Müller (glial) cells isolated from the tiger salamander retina. A novel chamber enabled stable recordings using H + -selective microelectrodes in a self-referencing format using bicarbonate-based buffer solutions. A small basal H + flux was observed from the end foot region of quiescent cells bathed in 24 mM bicarbonate-based solutions, and increasing extracellular potassium induced a dose-dependent increase in H + flux. Barium at 6 mM also increased H + flux. Potassium-induced extracellular acidifications were abolished when bicarbonate was replaced by 1 mM HEPES. The carbonic anhydrase antagonist benzolamide potentiated the potassium-induced extracellular acidification, while 300 μM DIDS, 300 μM SITS, and 30 μM S0859 significantly reduced the response. Potassium-induced extracellular acidifications persisted in solutions lacking extracellular calcium, although potassium-induced changes in intracellular calcium monitored with Oregon Green were abolished. Exchange of external sodium with choline also eliminated the potassium-induced extracellular acidification. Removal of extracellular sodium by itself induced a transient alkalinization, and replacement of sodium induced a transient acidification, both of which were blocked by 300 μM DIDS. Recordings at the apical portion of the cell showed smaller potassium-induced extracellular H + fluxes, and removal of the end foot region further decreased the H + flux, suggesting that the end foot was the major source of acidifications. These studies demonstrate that self-referencing H + -selective electrodes can be used to monitor H + fluxes from retinal Müller cells in bicarbonate-based solutions and confirm the presence of a sodium-coupled bicarbonate transporter, the activity of which is largely restricted to the end foot of the cell. NEW & NOTEWORTHY The present study uses self-referencing H + -selective electrodes for the

Oviposition site of the southern torrent salamander (Rhyacotriton variegatus) in northwestern California

Treesearch

Nancy E. Karraker; Lisa M. Ollivier; Garth R. Hodgson

2005-01-01

Oviposition sites and reproductive ecology of the southern-torrent salamander (Rhyacotriton variegatus) remain poorly documented. This species oviposits in cryptic locations making the detection of eggs difficult. Here we describe the discovery of 1 clutch of eggs of R. variegatus from northern California, which further expands our...

Determining sex and life stage of Del Norte salamanders from external cues

Treesearch

Lisa Ollivier; Hartwell H. Welsh Jr

2003-01-01

Life stage determination for many western plethodontids often requires dissection of the specimen. Availability of reliable external measures that could be applied under field conditions would enhance future studies of the genus Plethodon. We examined preserved specimens of the Del Norte Salamander, Plethodon elongatus, taken from...

Müller glial cells contribute to dim light vision in the spectacled caiman (Caiman crocodilus fuscus): Analysis of retinal light transmission.

PubMed

Agte, Silke; Savvinov, Alexey; Karl, Anett; Zayas-Santiago, Astrid; Ulbricht, Elke; Makarov, Vladimir I; Reichenbach, Andreas; Bringmann, Andreas; Skatchkov, Serguei N

2018-05-16

In this study, we show the capability of Müller glial cells to transport light through the inverted retina of reptiles, specifically the retina of the spectacled caimans. Thus, confirming that Müller cells of lower vertebrates also improve retinal light transmission. Confocal imaging of freshly isolated retinal wholemounts, that preserved the refractive index landscape of the tissue, indicated that the retina of the spectacled caiman is adapted for vision under dim light conditions. For light transmission experiments, we used a setup with two axially aligned objectives imaging the retina from both sides to project the light onto the inner (vitreal) surface and to detect the transmitted light behind the retina at the receptor layer. Simultaneously, a confocal microscope obtained images of the Müller cells embedded within the vital tissue. Projections of light onto several representative Müller cell trunks within the inner plexiform layer, i.e. (i) trunks with a straight orientation, (ii) trunks which are formed by the inner processes and (iii) trunks which get split into inner processes, were associated with increases in the intensity of the transmitted light. Projections of light onto the periphery of the Müller cell endfeet resulted in a lower intensity of transmitted light. In this way, retinal glial (Müller) cells support dim light vision by improving the signal-to-noise ratio which increases the sensitivity to light. The field of illuminated photoreceptors mainly include rods reflecting the rod dominance of the of tissue. A subpopulation of Müller cells with downstreaming cone cells led to a high-intensity illumination of the cones, while the surrounding rods were illuminated by light of lower intensity. Therefore, Müller cells that lie in front of cones may adapt the intensity of the transmitted light to the different sensitivities of cones and rods, presumably allowing a simultaneous vision with both receptor types under dim light conditions

Identification of a Novel Mutation in the ABCA4 Gene in a Chinese Family with Retinitis Pigmentosa Using Exome Sequencing.

PubMed

Huang, Xiangjun; Yuan, Lamei; Xu, Hongbo; Zheng, Wen; Cao, Yanna; Yi, Junhui; Guo, Yi; Yang, Zhijian; Li, Yu; Deng, Hao

2018-02-05

Retinitis pigmentosa (RP) is a group of hereditary, degenerative retinal disorders characterized by progressive retinal dysfunction, outer retina cell loss, and retinal tissue atrophy. It eventually leads to tunnel vision and legal, or total blindness. Here we aimed to reveal the causal gene and mutation contributing to the development of autosomal recessive RP (arRP) in a consanguineous family. A novel homozygous mutation, c.4845delT (p.K1616Rfs*46), in the ATP-binding cassette subfamily A member 4gene ( ABCA4 ) was identified. It may reduce ABCA4 protein activity, leading to progressive degeneration of both rod and cone photoreceptors. The study extends the arRP genotypic spectrum and confirms a genotype-phenotype relationship. This study may also disclose some new clues for RP genetic causes and pathogenesis, as well as clinical and genetic diagnosis. The research findings may contribute to improvement in clinical care, therapy, genetic screening, and counseling. ©2018 The Author(s).

Inhibiting autophagy reduces retinal degeneration caused by protein misfolding.

PubMed

Yao, Jingyu; Qiu, Yaoyan; Frontera, Eric; Jia, Lin; Khan, Naheed W; Klionsky, Daniel J; Ferguson, Thomas A; Thompson, Debra A; Zacks, David N

2018-06-25

Mutations in the genes necessary for the structure and function of vertebrate photoreceptor cells are associated with multiple forms of inherited retinal degeneration. Mutations in the gene encoding RHO (rhodopsin) are a common cause of autosomal dominant retinitis pigmentosa (adRP), with the Pro23His variant of RHO resulting in a misfolded protein that activates endoplasmic reticulum stress and the unfolded protein response. Stimulating macroautophagy/autophagy has been proposed as a strategy for clearing misfolded RHO and reducing photoreceptor death. We found that retinas from mice heterozygous for the gene encoding the RHO P23H variant (hereafter called P23H) exhibited elevated levels of autophagy flux, and that pharmacological stimulation of autophagy accelerated retinal degeneration. In contrast, reducing autophagy flux pharmacologically or by rod-specific deletion of the autophagy-activating gene Atg5, improved photoreceptor structure and function. Furthermore, proteasome levels and activity were reduced in the P23H retina, and increased when Atg5 was deleted. Our findings suggest that autophagy contributes to photoreceptor cell death in P23H mice, and that decreasing autophagy shifts the degradation of misfolded RHO protein to the proteasome and is protective. These observations suggest that modulating the flux of misfolded proteins from autophagy to the proteasome may represent an important therapeutic strategy for reducing proteotoxicity in adRP and other diseases caused by protein folding defects.

Pupillometer-based objective chromatic perimetry in normal eyes and patients with retinal photoreceptor dystrophies.

PubMed

Skaat, Alon; Sher, Ifat; Kolker, Andrew; Elyasiv, Sivan; Rosenfeld, Elkana; Mhajna, Mohamad; Melamed, Shlomo; Belkin, Michael; Rotenstreich, Ygal

2013-04-17

To evaluate a novel objective perimetry using multifocal chromatic pupil light reflex in normal participants and patients with photoreceptor dysfunction, and to relate this new technique with subjective dark-adapted chromatic Goldmann perimetry. Thirty-two eyes of 17 retinitis pigmentosa (RP) or cone-rod dystrophy patients and 20 eyes of 12 healthy individuals were tested. A computerized infrared video pupillometer was used to record changes in pupil diameter in response to short- and long-wavelength stimuli (peak 485 and 640 nm, respectively; light intensity 40 cd/m(2)) at 13 different points of the 30° visual field (VF), under background illumination of 2.7 cd/m(2). The pupillary response (PR) of patients was compared with PR obtained from normal control participants. In 11 patients, the pupillary responses were also compared with their findings on dark-adapted chromatic Goldmann perimetry. Significantly reduced pupillary responses were obtained in RP patients in response to the short-wavelength stimulus in nearly all perimetric locations (P < 0.03). By contrast, in response to the long-wavelength stimulus, RP patients demonstrated significantly reduced PR mostly in peripheral locations (P ≤ 0.02). In a cone-rod dystrophy patient, the PR to both long- and short-wavelength stimuli was significantly lower in the scotoma area identified by the dark-adapted chromatic Goldmann perimetry. In all patients that were tested by the chromatic Goldmann, minimal PR was recorded in areas that were nondetected in the chromatic Goldmann perimetry. This study demonstrates the potential feasibility of using pupillometer-based chromatic perimetry for objectively assessing VF defects and retinal function in patients with retinal dystrophies. (ClinicalTrials.gov number, NCT01021982.).

Retinal Oximetry Discovers Novel Biomarkers in Retinal and Brain Diseases.

PubMed

Stefánsson, Einar; Olafsdottir, Olof Birna; Einarsdottir, Anna Bryndis; Eliasdottir, Thorunn Scheving; Eysteinsson, Thor; Vehmeijer, Wouter; Vandewalle, Evelien; Bek, Toke; Hardarson, Sveinn Hakon

2017-05-01

Biomarkers for several eye and brain diseases are reviewed, where retinal oximetry may help confirm diagnosis or measure severity of disease. These include diabetic retinopathy, central retinal vein occlusion (CRVO), retinitis pigmentosa, glaucoma, and Alzheimer's disease. Retinal oximetry is based on spectrophotometric fundus imaging and measures oxygen saturation in retinal arterioles and venules in a noninvasive, quick, safe manner. Retinal oximetry detects changes in oxygen metabolism, including those that result from ischemia or atrophy. In diabetic retinopathy, venous oxygen saturation increases and arteriovenous difference decreases. Both correlate with diabetic retinopathy severity as conventionally classified on fundus photographs. In CRVO, vein occlusion causes hypoxia, which is measured directly by retinal oximetry to confirm the diagnosis and measure severity. In both diseases, the change in oxygen levels is a consequence of disturbed blood flow with resulting tissue hypoxia and vascular endothelial growth factor (VEGF) production. In atrophic diseases, such as retinitis pigmentosa and glaucoma, retinal oxygen consumption is reduced and this is detected by retinal oximetry. Retinal oximetry correlates with visual field damage and retinal atrophy. It is an objective metabolic measure of the degree of retinal atrophy. Finally, the retina is part of the central nervous system tissue and reflects central nervous system diseases. In Alzheimer's disease, a change in retinal oxygen metabolism has been discovered. Retinal oximetry is a novel, noninvasive technology that opens the field of metabolic imaging of the retina. Biomarkers in metabolic, ischemic, and atrophic diseases of the retina and central nervous system have been discovered.

Retinal Vasculitis

PubMed Central

Rosenbaum, James T.; Sibley, Cailin H.; Lin, Phoebe

2016-01-01

Purpose of review Ophthalmologists and rheumatologists frequently miscommunicate in consulting on patients with retinal vasculitis. This report seeks to establish a common understanding of the term, retinal vasculitis, and to review recent papers on this diagnosis. Recent findings 1) The genetic basis of some rare forms of retinal vascular disease have recently been described. Identified genes include CAPN5, TREX1, and TNFAIP3; 2) Behçet’s disease is a systemic illness that is very commonly associated with occlusive retinal vasculitis; 3) retinal imaging including fluorescein angiography and other newer imaging modalities has proven crucial to the identification and characterization of retinal vasculitis and its complications; 4) although monoclonal antibodies to IL-17A or IL-1 beta failed in trials for Behçet’s disease, antibodies to TNF alpha, either infliximab or adalimumab, have demonstrated consistent benefit in managing this disease. Interferon treatment and B cell depletion therapy via rituximab may be beneficial in certain types of retinal vasculitis. Summary Retinal vasculitis is an important entity for rheumatologists to understand. Retinal vasculitis associated with Behçet’s disease responds to monoclonal antibodies that neutralize TNF, but the many other forms of non-infectious retinal vasculitis may require alternate therapeutic management. PMID:26945335

Interactive effects of temperature and glyphosate on the behavior of blue ridge two-lined salamanders (Eurycea wilderae).

PubMed

Gandhi, Jaina S; Cecala, Kristen K

2016-09-01

The objective of the present study was to evaluate the potential interactive effects of stream temperatures and environmentally relevant glyphosate-based herbicide concentrations on movement and antipredator behaviors of larval Eurycea wilderae (Blue Ridge two-lined salamander). Larval salamanders were exposed to 1 of 4 environmentally relevant glyphosate concentrations (0.00 µg acid equivalent [a.e.]/L, 0.73 µg a.e./L, 1.46 µg a.e./L, and 2.92 µg a.e./L) at either ambient (12 °C) or elevated (23 °C) water temperature. Behaviors observed included the exploration of a novel habitat, use of refuge, habitat selection relative to a potential predator, and burst movement distance. In the absence of glyphosate, temperature consistently affected movement and refuge-use behavior, with individuals moving longer distances more frequently and using refuge less at warm temperatures; however, when glyphosate was added, the authors observed inconsistent effects of temperature that may have resulted from differential toxicity at various temperatures. Larval salamanders made shorter, more frequent movements and demonstrated reduced burst distance at higher glyphosate concentrations. The authors also found that lower glyphosate concentrations sometimes had stronger effects than higher concentrations (i.e., nonmonotonic dose responses), suggesting that standard safety tests conducted only at higher glyphosate concentrations might overlook important sublethal effects on salamander behavior. These data demonstrate that sublethal effects of glyphosate-based herbicides on natural behaviors of amphibians can occur with short-term exposure to environmentally relevant concentrations. Environ Toxicol Chem 2016;35:2297-2303. © 2016 SETAC. © 2016 SETAC.

Landscape influences on dispersal behaviour: a theoretical model and empirical test using the fire salamander, Salamandra infraimmaculata.

PubMed

Kershenbaum, Arik; Blank, Lior; Sinai, Iftach; Merilä, Juha; Blaustein, Leon; Templeton, Alan R

2014-06-01

When populations reside within a heterogeneous landscape, isolation by distance may not be a good predictor of genetic divergence if dispersal behaviour and therefore gene flow depend on landscape features. Commonly used approaches linking landscape features to gene flow include the least cost path (LCP), random walk (RW), and isolation by resistance (IBR) models. However, none of these models is likely to be the most appropriate for all species and in all environments. We compared the performance of LCP, RW and IBR models of dispersal with the aid of simulations conducted on artificially generated landscapes. We also applied each model to empirical data on the landscape genetics of the endangered fire salamander, Salamandra infraimmaculata, in northern Israel, where conservation planning requires an understanding of the dispersal corridors. Our simulations demonstrate that wide dispersal corridors of the low-cost environment facilitate dispersal in the IBR model, but inhibit dispersal in the RW model. In our empirical study, IBR explained the genetic divergence better than the LCP and RW models (partial Mantel correlation 0.413 for IBR, compared to 0.212 for LCP, and 0.340 for RW). Overall dispersal cost in salamanders was also well predicted by landscape feature slope steepness (76%), and elevation (24%). We conclude that fire salamander dispersal is well characterised by IBR predictions. Together with our simulation findings, these results indicate that wide dispersal corridors facilitate, rather than hinder, salamander dispersal. Comparison of genetic data to dispersal model outputs can be a useful technique in inferring dispersal behaviour from population genetic data.

Membrane current of retinal rods of Caudiverbera caudiverbera (Amphibia: Leptodactylidae): dark noise, spectral and absolute light sensitivity.

PubMed

Palma, F; Roncagliolo, P; Bacigalupo, J; Palacios, A G

2001-01-01

We investigated the photocurrents from isolated rods of the South American anuran, Caudiverbera caudiverbera. Rod outer segments were on average 66.4 +/- 11.2 microm (mean +/- S.D., n = 104) in length and 6.6 +/- 0.9 microm (mean +/- S.D.) in diameter: 40 +/- 22 photoisomerizations (mean +/- S.D., range 10-99, n = 16) were required for eliciting a half-saturating photocurrent response. The time-to-peak was 911 +/- 217 ms (mean +/- S.D., n = 14, 20 degrees C) in the linear range of the response and the integration time of the current response was 1744 +/- 451 ms (mean +/- S.D., n = 14). The time-to-peak appears to be slower and the integration time shorter in Caudiverbera than in Ambystoma tigrinum, Rana pipiens or Xenopus laevis rods under similar experimental conditions. The a-band of rod spectral sensitivity has a lambda(max) at 520 +/- 2.1 nm (mean +/- S.D., range 516-525 nm, n = 24) and the bandwidth fits a porphyropsin visual pigment. The single-event response amplitude ranges from 0.31-0.51 pA, depending on the calculation method. The intrinsic dark current (variance at dark minus variance under bright light) was 0.045 +/- 0.040 pA2 (mean +/- S.D., n = 24). Our results support the presence of a dark-noise component below 1 Hz, with kinetics similar to the single-photon evoked response and a rate of 0.006 events s(-1) (n = 9).

3D Bite Modeling and Feeding Mechanics of the Largest Living Amphibian, the Chinese Giant Salamander Andrias davidianus (Amphibia:Urodela)

PubMed Central

Fortuny, Josep; Marcé-Nogué, Jordi; Heiss, Egon; Sanchez, Montserrat; Gil, Lluis; Galobart, Àngel

2015-01-01

Biting is an integral feature of the feeding mechanism for aquatic and terrestrial salamanders to capture, fix or immobilize elusive or struggling prey. However, little information is available on how it works and the functional implications of this biting system in amphibians although such approaches might be essential to understand feeding systems performed by early tetrapods. Herein, the skull biomechanics of the Chinese giant salamander, Andrias davidianus is investigated using 3D finite element analysis. The results reveal that the prey contact position is crucial for the structural performance of the skull, which is probably related to the lack of a bony bridge between the posterior end of the maxilla and the anterior quadrato-squamosal region. Giant salamanders perform asymmetrical strikes. These strikes are unusual and specialized behavior but might indeed be beneficial in such sit-and-wait or ambush-predators to capture laterally approaching prey. However, once captured by an asymmetrical strike, large, elusive and struggling prey have to be brought to the anterior jaw region to be subdued by a strong bite. Given their basal position within extant salamanders and their “conservative” morphology, cryptobranchids may be useful models to reconstruct the feeding ecology and biomechanics of different members of early tetrapods and amphibians, with similar osteological and myological constraints. PMID:25853557

Targeted Ablation of the Pde6h Gene in Mice Reveals Cross-species Differences in Cone and Rod Phototransduction Protein Isoform Inventory*

PubMed Central

Brennenstuhl, Christina; Tanimoto, Naoyuki; Burkard, Markus; Wagner, Rebecca; Bolz, Sylvia; Trifunovic, Dragana; Kabagema-Bilan, Clement; Paquet-Durand, Francois; Beck, Susanne C.; Huber, Gesine; Seeliger, Mathias W.; Ruth, Peter; Wissinger, Bernd; Lukowski, Robert

2015-01-01

Phosphodiesterase-6 (PDE6) is a multisubunit enzyme that plays a key role in the visual transduction cascade in rod and cone photoreceptors. Each type of photoreceptor utilizes discrete catalytic and inhibitory PDE6 subunits to fulfill its physiological tasks, i.e. the degradation of cyclic guanosine-3′,5′-monophosphate at specifically tuned rates and kinetics. Recently, the human PDE6H gene was identified as a novel locus for autosomal recessive (incomplete) color blindness. However, the three different classes of cones were not affected to the same extent. Short wave cone function was more preserved than middle and long wave cone function indicating that some basic regulation of the PDE6 multisubunit enzyme was maintained albeit by a unknown mechanism. To study normal and disease-related functions of cone Pde6h in vivo, we generated Pde6h knock-out (Pde6h−/−) mice. Expression of PDE6H in murine eyes was restricted to both outer segments and synaptic terminals of short and long/middle cone photoreceptors, whereas Pde6h−/− retinae remained PDE6H-negative. Combined in vivo assessment of retinal morphology with histomorphological analyses revealed a normal overall integrity of the retinal organization and an unaltered distribution of the different cone photoreceptor subtypes upon Pde6h ablation. In contrast to human patients, our electroretinographic examinations of Pde6h−/− mice suggest no defects in cone/rod-driven retinal signaling and therefore preserved visual functions. To this end, we were able to demonstrate the presence of rod PDE6G in cones indicating functional substitution of PDE6. The disparities between human and murine phenotypes caused by mutant Pde6h/PDE6H suggest species-to-species differences in the vulnerability of biochemical and neurosensory pathways of the visual signal transduction system. PMID:25739440

Confirmation of the genetic heterogeneity of retinitis pigmentosa: Linkage analyses of the beta-subunit of rod phosphodiesterase (PDEB) in ten families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kojis, T.L.; Heinzmann, C.; Bateman, J.B.

1994-09-01

Mutations in the gene for the {beta}-subunit of the human rod photoreceptor cGMP phosphodiesterase (PDEB) are responsible for some recessively inherited cases of retinitis pigmentosa (RP). The gene has been localized to human chromosome 4p16.3, near the Huntington disease locus (IT15), by in situ hybridization, somatic cell hybrid and linkage mapping. We previously identified and characterized RFLPs within PDEB, which we have used to establish the linkage relationships with nine other chromosome 4p16 markers in the CEPH v.6.0 database; the most likely locus order is D4S90-[PDEB-D4S115-D4S43]-[D4S95-D4S125]-IT15-[D4S126-D4S412]-D4S10. Using a combination of PDEB RFLPs and microsatellite variation in these linked marker loci,more » we analyzed ten families manifesting autosomal forms of RP for linkage to the PDEB reigon. PDEB was excluded as the disease-causing gene in three autosomal dominant (AD) RP families using PDEB RFLPs. While linkage to PDEB itself could not be ruled out, tight linkage to two closely linked markers (D4S115 and D4S43) was excluded in two additional AD and in three of five autosomal recessive (AR) RP families. Our data provide further evidence for the genetic heterogeneity in families with autosomal forms of RP.« less

Biodiversity of Costa Rican salamanders: Implications of high levels of genetic differentiation and phylogeographic structure for species formation

PubMed Central

García-París, Mario; Good, David A.; Parra-Olea, Gabriela; Wake, David B.

2000-01-01

Although salamanders are characteristic amphibians in Holarctic temperate habitats, in tropical regions they have diversified evolutionarily only in tropical America. An adaptive radiation centered in Middle America occurred late in the history of a single clade, the supergenus Bolitoglossa (Plethodontidae), and large numbers of species now occur in diverse habitats. Sublineages within this clade decrease in number from the northern to southern parts of Middle America, and in Costa Rica, there are but three. Despite this phylogenetic constraint, Costa Rica has many species; the number of salamander species on one local elevational transect in the Cordillera de Talamanca may be the largest for any such transect in the world. Extraordinary variation in sequences of the mitochondrial gene cytochrome b within a clade of the genus Bolitoglossa in Costa Rica reveals strong phylogeographic structure within a single species, Bolitoglossa pesrubra. Allozymic variation in 19 proteins reveals a pattern largely concordant with the mitochondrial DNA phylogeography. More species exist than are currently recognized. Diversification occurs in restricted geographic areas and involves sharp geographic and elevational differentiation and zonation. In their degree of genetic differentiation at a local scale, these species of the deep tropics exceed the known variation of extratropical salamanders, which also differ in being less restricted in elevational range. Salamanders display “tropicality” in that although speciose, they are usually local in distribution and rare. They display strong ecological and physiological differentiation that may contribute importantly to morphological divergence and species formation. PMID:10677512