Loss of BCL-XLin Rod Photoreceptors: Increased Susceptibility to Bright Light Stress

2006 ◽  
Vol 47 (12) ◽  
pp. 5583 ◽  
Author(s):  
Lixin Zheng ◽  
Robert E. Anderson ◽  
Martin-Paul Agbaga ◽  
Edmund B. Rucker ◽  
Yun-Zheng Le
Keyword(s):  
Light Stress ◽  
Bright Light ◽  
Rod Photoreceptors ◽  
Increased Susceptibility

CGRP-dependent and independent mechanisms of acute and persistent post-traumatic headache following mild traumatic brain injury in mice

Cephalalgia ◽  
2019 ◽  
Vol 39 (14) ◽  
pp. 1762-1775 ◽  
Author(s):  
Edita Navratilova ◽  
Jill Rau ◽  
Janice Oyarzo ◽  
Jason Tien ◽  
Kimberly Mackenzie ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Light Stress ◽  
Bright Light ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Cutaneous Allodynia ◽  
Calcitonin Gene ◽  
Post Traumatic

Background Acute and persistent post-traumatic headache are often debilitating consequences of traumatic brain injury. Underlying physiological mechanisms of post-traumatic headache and its persistence remain unknown, and there are currently no approved therapies for these conditions. Post-traumatic headache often presents with a migraine-like phenotype. As calcitonin-gene related peptide promotes migraine headache, we explored the efficacy and timing of intervention with an anti- calcitonin-gene related peptide monoclonal antibody in novel preclinical models of acute post-traumatic headache and persistent post-traumatic headache following a mild traumatic brain injury event in mice. Methods Male, C57Bl/6 J mice received a sham procedure or mild traumatic brain injury resulting from a weight drop that allowed free head rotation while under minimal anesthesia. Periorbital and hindpaw tactile stimulation were used to assess mild traumatic brain injury-induced cutaneous allodynia. Two weeks after the injury, mice were challenged with stress, a common aggravator of migraine and post-traumatic headache, by exposure to bright lights (i.e. bright light stress) and cutaneous allodynia was measured hourly for 5 hours. A murine anti- calcitonin-gene related peptide monoclonal antibody was administered after mild traumatic brain injury at different time points to allow evaluation of the consequences of either early and sustained calcitonin-gene related peptide sequestration or late administration only prior to bright light stress. Results Mice with mild traumatic brain injury, but not a sham procedure, exhibited both periorbital and hindpaw cutaneous allodynia that resolved by post-injury day 13. Following resolution of injury-induced cutaneous allodynia, exposure to bright light stress re-instated periorbital and hindpaw cutaneous allodynia in injured, but not sham mice. Repeated administration of anti-calcitonin-gene related peptide monoclonal antibody at 2 hours, 7 and 14 days post mild traumatic brain injury significantly attenuated the expression of cutaneous allodynia when evaluated over the 14-day post injury time course and also prevented bright light stress-induced cutaneous allodynia in injured mice. Administration of anti-calcitonin-gene related peptide monoclonal antibody only at 2 hours and 7 days after mild traumatic brain injury blocked injury-induced cutaneous allodynia and partially prevented bright light stress-induced cutaneous allodynia. A single administration of anti-calcitonin-gene related peptide monoclonal antibody after the resolution of the peak injury-induced cutaneous allodynia, but prior to bright light stress challenge, did not prevent bright light stress-induced cutaneous allodynia. Conclusions We used a clinically relevant mild traumatic brain injury event in mice along with a provocative stimulus as novel models of acute post-traumatic headache and persistent post-traumatic headache. Following mild traumatic brain injury, mice demonstrated transient periorbital and hindpaw cutaneous allodynia suggestive of post-traumatic headache-related pain and establishment of central sensitization. Following resolution of injury-induced cutaneous allodynia, exposure to bright light stress re-established cutaneous allodynia, suggestive of persistent post-traumatic headache-related pain. Continuous early sequestration of calcitonin-gene related peptide prevented both acute post-traumatic headache and persistent post-traumatic headache. In contrast, delayed anti-calcitonin-gene related peptide monoclonal antibody treatment following establishment of central sensitization was ineffective in preventing persistent post-traumatic headache. These observations suggest that mechanisms involving calcitonin-gene related peptide underlie the expression of acute post-traumatic headache, and drive the development of central sensitization, increasing vulnerability to headache triggers and promoting persistent post-traumatic headache. Early and continuous calcitonin-gene related peptide blockade following mild traumatic brain injury may represent a viable treatment option for post-traumatic headache and for the prevention of post-traumatic headache persistence. Abbreviations CA Cutaneous allodynia CGRP Calcitonin gene-related peptide mTBI Mild traumatic brain injury PTH Post-traumatic headache APTH Acute post-traumatic headache PPTH Persistent post-traumatic headache

Effect of hydroxylamine on the subcellular distribution of arrestin (S-antigen) in rod photoreceptors

1994 ◽  
Vol 11 (3) ◽  
pp. 561-568 ◽  
Author(s):  
Nancy J. Mangini ◽  
Grady L. Garner ◽  
Tinging L. Okajima ◽  
Larry A. Donoso ◽  
David R. Pepperberg
Keyword(s):  
Visual Pigment ◽  
Driving Force ◽  
Outer Segment ◽  
Processing System ◽  
Bright Light ◽  
Photoreceptor Outer Segment ◽  
Rod Photoreceptors ◽  
Average Value ◽  
Secondary Antibodies ◽  
Microscopic Image Processing

AbstractThe immunocytochemical labeling of arrestin (S-antigen) in photoreceptors of the ovine retina was examined following incubation of the retina with hydroxylamine (NH2OH), an agent known to inhibit the phosphorylation of photoactivated rhodopsin. Intact, isolated retinas bathed in medium containing 20 mM NH2OH, or in control medium lacking NH2OH, were maintained in darkness or exposed to bright light for 3 min (dark-adapted and light-adapted conditions, respectively); further incubated in darkness for 10 min; and then fixed and prepared for cryosectioning. Cryosections were incubated with anti-S-antigen monoclonal antibody MAb A2G5; with secondary antibodies that were conjugated with horseradish peroxidase; and with either 3–amino-9–ethyl carbazole or diaminobenzidine as chromogen. Anti-arrestin labeling in cryosections was then analyzed densitometrically using a light-microscopic image processing system. In dark-adapted control retinas, labeling density of the photoreceptor outer segment (OS) layer (0.061 ± 0.004; average ± S.e.m.) was less than that of the inner segment (IS) layer (0.138 ± 0.011). In light-adapted control retinas, OS labeling density (0.139 ± 0.007) exceeded IS labeling density (0.095 ± 0.005). Incubation with NH2OH eliminated this light-dependent increase in labeling of the OS relative to that of the IS, i.e. eliminated the increase in relative OS/IS labeling. Densities of labeling were 0.110 ± 0.006 (OS) and 0.183 ± 0.006 (IS) in NH2OH-treated dark-adapted retinas vs. 0.078 ± 0.004 (OS) and 0.182 ± 0.008 (IS) in NH2OH-treated light-adapted retinas. Anti-arrestin labeling was also examined in retinas that were exposed to 3 min or 13 min of bright light and then immediately fixed. Among retinas incubated in the absence of NH2OH, an increase in OS/IS labeling density was evident after 3 min of illumination, and retinas illuminated for 13 min exhibited an even larger increase in OS/IS labeling. An increase in OS/IS labeling was also exhibited by NH2OH-treated retinas that had been illuminated for 3 min; by comparison with dark-adapted NH2OH-treated controls (average value of OS/IS labeling: 0.60), OS/IS labeling in these illuminated retinas was 0.97. However, OS/IS labeling in NH2OH-treated retinas that had been illuminated for 13 min (average value: 0.35) was lower than that of the dark-adapted controls. The results indicate that, within intact rods, NH2OH inhibits the light-dependent increase in OS/IS anti-arrestin labeling that is ordinarily expressed at long times (~10 min) after major bleaching of the visual pigment. Among the possible bases for the effect of NH2OH are a reduction in the driving force for the movement of arrestin from the inner to the outer segment and/or a facilitation of the degradation of arrestin in the outer segment.

scholarly journals Occupancy of the Chromophore Binding Site of Opsin Activates Visual Transduction in Rod Photoreceptors

1999 ◽  
Vol 113 (3) ◽  
pp. 491-503 ◽  
Author(s):  
Vladimir J. Kefalov ◽  
M. Carter Cornwall ◽  
Rosalie K. Crouch
Keyword(s):  
Binding Site ◽  
Bright Light ◽  
Direct Interaction ◽  
Light Sensitivity ◽  
Noncovalent Interaction ◽  
Covalent Attachment ◽  
Physiological Data ◽  
Similar Reaction ◽  
Rod Photoreceptors ◽  
Cone Opsin

The retinal analogue β-ionone was used to investigate possible physiological effects of the noncovalent interaction between rod opsin and its chromophore 11-cis retinal. Isolated salamander rod photoreceptors were exposed to bright light that bleached a significant fraction of their pigment, were allowed to recover to a steady state, and then were exposed to β-ionone. Our experiments show that in bleach-adapted rods β-ionone causes a decrease in light sensitivity and dark current and an acceleration of the dim flash photoresponse and the rate constants of guanylyl cyclase and cGMP phosphodiesterase. Together, these observations indicate that in bleach-adapted rods β-ionone activates phototransduction in the dark. Control experiments showed no effect of β-ionone in either fully dark-adapted or background light-adapted cells, indicating direct interaction of β-ionone with the free opsin produced by bleaching. We speculate that β-ionone binds specifically in the chromophore pocket of opsin to produce a complex that is more catalytically potent than free opsin alone. We hypothesize that a similar reaction may occur in the intact retina during pigment regeneration. We propose a model of rod pigment regeneration in which binding of 11-cis retinal to opsin leads to activation of the complex accompanied by a decrease in light sensitivity. The subsequent covalent attachment of retinal to opsin completely inactivates opsin and leads to the recovery of sensitivity. Our findings resolve the conflict between biochemical and physiological data concerning the effect of the occupancy of the chromophore binding site on the catalytic potency of opsin. We show that binding of β-ionone to rod opsin produces effects opposite to its previously described effects on cone opsin. We propose that this distinction is due to a fundamental difference in the interaction of rod and cone opsins with retinal, which may have implications for the different physiology of the two types of photoreceptors.

scholarly journals The evolution of rod photoreceptors

2017 ◽  
Vol 372 (1717) ◽  
pp. 20160074 ◽  
Author(s):  
Ala Morshedian ◽  
Gordon L. Fain
Keyword(s):  
Entire Range ◽  
Selection Pressure ◽  
Outer Segment ◽  
Bright Light ◽  
Protein Isoforms ◽  
Single Photons ◽  
Rod Photoreceptors ◽  
Present Evidence ◽  
Dim Light ◽  
Novel Protein

Photoreceptors in animals are generally of two kinds: the ciliary or c-type and the rhabdomeric or r-type. Although ciliary photoreceptors are found in many phyla, vertebrates seem to be unique in having two distinct kinds which together span the entire range of vision, from single photons to bright light. We ask why the principal photoreceptors of vertebrates are ciliary and not rhabdomeric, and how rods evolved from less sensitive cone-like photoreceptors to produce our duplex retina. We suggest that the principal advantage of vertebrate ciliary receptors is that they use less ATP than rhabdomeric photoreceptors. This difference may have provided sufficient selection pressure for the development of a completely ciliary eye. Although many of the details of rod evolution are still uncertain, present evidence indicates that (i) rods evolved very early before the split between the jawed and jawless vertebrates, (ii) outer-segment discs make no contribution to rod sensitivity but may have evolved to increase the efficiency of protein renewal, and (iii) evolution of the rod was incremental and multifaceted, produced by the formation of several novel protein isoforms and by changes in protein expression, with no one alteration having more than a few-fold effect on transduction activation or inactivation. This article is part of the themed issue ‘Vision in dim light’.

scholarly journals Characterization of a zebra Mutant of Rice with Increased Susceptibility to Light Stress

2000 ◽  
Vol 41 (2) ◽  
pp. 158-164 ◽  
Author(s):  
K. Kusumi ◽  
H. Komori ◽  
H. Satoh ◽  
K. Iba
Keyword(s):  
Light Stress ◽  
Increased Susceptibility

scholarly journals Rod Photoreceptors Avoid Saturation in Bright Light by the Movement of the G Protein Transducin

2021 ◽  
Vol 41 (15) ◽  
pp. 3320-3330
Author(s):  
Rikard Frederiksen ◽  
Ala Morshedian ◽  
Sonia A. Tripathy ◽  
Tongzhou Xu ◽  
Gabriel H. Travis ◽  
...  
Keyword(s):  
G Protein ◽  
Bright Light ◽  
Rod Photoreceptors

Flexibility in the colouration of the meninx (brain covering) in the guppy (Poecilia reticulata): investigations of potential function

2009 ◽  
Vol 87 (6) ◽  
pp. 529-536 ◽  
Author(s):  
R. Gibson ◽  
J. G. Burns ◽  
F. H. Rodd
Keyword(s):  
Poecilia Reticulata ◽  
Light Stress ◽  
Colour Change ◽  
Bright Light ◽  
Avian Predators ◽  
Light Levels ◽  
Primary Hypothesis ◽  
Predator Model ◽  
Physiological Colour Change ◽  
Apparent Colour

Many organisms can change the apparent colour of their bodies by altering the aggregation of pigment in chromatophores in a process known as physiological colour change. In this study, we investigate a previously unstudied example of physiological colour change, from clear to black, of a brain covering, or meninx, in the guppy ( Poecilia reticulata Peters, 1859). UV protection in bright light was our primary hypothesis for the function of the meningeal colour, with a cost of increased conspicuousness to avian predators selecting for plasticity in the trait. An alternate hypothesis was that this flexible trait could be a physiological by-product of stress. Thus, we investigated the response of meningeal colour to light, stress, and simulated predator attacks, and also whether the black meninx affected conspicuousness to potential predators. Meningeal response to higher light levels did not differ from baseline responses. However, we did find that stress induced a sex-biased, rapid darkening of the meninx; this darkening then declined over time. These results suggest that meningeal blackness could be used as a novel, noninvasive indicator of stress level in guppies. We found no evidence for a role of predation in meningeal colour: meninx colour did not respond to the presence of a predator model and human “predators” detected similar numbers of guppies with black meninges and guppies with clear meninges.

scholarly journals Physiological and Microfluorometric Studies of Reduction and Clearance of Retinal in Bleached Rod Photoreceptors

2004 ◽  
Vol 124 (4) ◽  
pp. 429-443 ◽  
Author(s):  
Efthymia Tsina ◽  
Chunhe Chen ◽  
Yiannis Koutalos ◽  
Petri Ala-Laurila ◽  
Marco Tsacopoulos ◽  
...  
Keyword(s):  
Dark Adaptation ◽  
Bright Light ◽  
Proximal Region ◽  
Rod Photoreceptors ◽  
Outer Segments ◽  
Interphotoreceptor Retinoid Binding Protein ◽  
Response Recovery ◽  
Electrophysiological Measurements ◽  
Rate Of Recovery ◽  
Flash Response

The visual cycle comprises a sequence of reactions that regenerate the visual pigment in photoreceptors during dark adaptation, starting with the reduction of all-trans retinal to all-trans retinol and its clearance from photoreceptors. We have followed the reduction of retinal and clearance of retinol within bleached outer segments of red rods isolated from salamander retina by measuring its intrinsic fluorescence. Following exposure to a bright light (bleach), increasing fluorescence intensity was observed to propagate along the outer segments in a direction from the proximal region adjacent to the inner segment toward the distal tip. Peak retinol fluorescence was achieved after ∼30 min, after which it declined very slowly. Clearance of retinol fluorescence is considerably accelerated by the presence of the exogenous lipophilic substances IRBP (interphotoreceptor retinoid binding protein) and serum albumin. We have used simultaneous fluorometric and electrophysiological measurements to compare the rate of reduction of all-trans retinal to all-trans retinol to the rate of recovery of flash response amplitude in these cells in the presence and absence of IRBP. We find that flash response recovery in rods is modestly accelerated in the presence of extracellular IRBP. These results suggest such substances may participate in the clearance of retinoids from rod photoreceptors, and that this clearance, at least in rods, may facilitate dark adaptation by accelerating the clearance of photoproducts of bleaching.

scholarly journals Increased susceptibility to cortical spreading depression in an animal model of medication-overuse headache

Cephalalgia ◽  
2013 ◽  
Vol 34 (8) ◽  
pp. 594-604 ◽  
Author(s):  
A Laine Green ◽  
Pengfei Gu ◽  
Milena De Felice ◽  
David Dodick ◽  
Michael H Ossipov ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Environmental Stress ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Bright Light ◽  
Sprague Dawley ◽  
Fos Expression ◽  
Increased Susceptibility

Objective The objective of this article is to evaluate electrically evoked thresholds for cortical spreading depression (CSD) and stress-induced activation of trigeminal afferents in a rat model of medication-overuse headache (MOH). Methods Sumatriptan or saline was delivered subcutaneously by osmotic minipump for six days to Sprague-Dawley rats. Two weeks after pump removal, animals were anesthetized and recording/stimulating electrodes implanted. The animals were pretreated with vehicle or topiramate followed by graded electrical stimulation within the visual cortex. CSD events were identified by decreased EEG amplitude and DC potential shift. Additional unanesthetized sumatriptan or saline-pretreated rats were exposed to bright light environmental stress and periorbital and hindpaw withdrawal thresholds were measured. Following CSD stimulation or environmental stress, immunohistochemical staining for Fos in the trigeminal nucleus caudalis (TNC) was performed. Results Sumatriptan pre-exposure significantly decreased electrical stimulation threshold to generate a CSD event. Topiramate normalized the decreased CSD threshold as well as stress-induced behavioral withdrawal thresholds in sumatriptan-treated rats compared to saline-treated animals. Moreover, CSD and environmental stress increased Fos expression in the TNC of sumatriptan-treated rats, and these effects were blocked by topiramate. Environmental stress did not elicit cutaneous allodynia or elevate TNC Fos expression in saline-treated rats. Conclusions A previous period of sumatriptan exposure produced long-lasting increased susceptibility to evoked CSD and environmental stress-induced activation of the TNC that was prevented by topiramate. Lowered CSD threshold, and enhanced consequences of CSD events (increased activation of TNC), may represent an underlying biological mechanism of MOH related to triptans.

scholarly journals Ubrogepant does not induce latent sensitization in a preclinical model of medication overuse headache

Cephalalgia ◽  
2020 ◽  
Vol 40 (9) ◽  
pp. 892-902 ◽  
Author(s):  
Edita Navratilova ◽  
Sasan Behravesh ◽  
Janice Oyarzo ◽  
David W Dodick ◽  
Pradeep Banerjee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Treatment ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Light Stress ◽  
Bright Light ◽  
Nitric Oxide Donor ◽  
Preclinical Model ◽  
Cutaneous Allodynia ◽  
Oral Doses

Background Ubrogepant, a small-molecule calcitonin gene-related peptide receptor antagonist, was recently approved as an oral medication for the acute treatment of migraine. This study aimed to determine whether ubrogepant shows efficacy in a preclinical model of migraine-like pain and whether repeated oral administration of ubrogepant induces latent sensitization relevant to medication overuse headache in rats. Methods A “two-hit” priming model of medication overuse headache was used. Female Sprague-Dawley rats received six oral doses of sumatriptan 10 mg/kg over 2 weeks to induce latent sensitization (i.e. “priming”). Cutaneous allodynia was measured periodically over 20 days in the periorbital and hindpaw regions using von Frey filaments. The rats were then subjected to a 1-hour bright light stress challenge on two consecutive days. At the start of the second bright light stress exposure, oral sumatriptan 10 mg/kg, oral ubrogepant 25, 50, or 100 mg/kg, or vehicle was administered; thereafter, cephalic and hindpaw sensory thresholds were monitored hourly over 5 hours to determine the efficacy of ubrogepant in reversing bright light stress-induced cutaneous allodynia. A dose of ubrogepant effective in the medication overuse headache model (100 mg/kg) was then selected to determine if repeated administration would produce latent sensitization. Rats were administered six oral doses of ubrogepant 100 mg/kg, sumatriptan 10 mg/kg (positive control), or vehicle over 2 weeks, and cutaneous allodynia was evaluated regularly. Testing continued until mechanosensitivity returned to baseline levels. Rats were then challenged with bright light stress on days 20 and 21, and periorbital and hindpaw cutaneous allodynia was measured. On days 28 to 32, the same groups received a nitric oxide donor (sodium nitroprusside 3 mg/kg, i.p.), and cutaneous allodynia was assessed hourly over 5 hours. Results Sumatriptan elicited cutaneous allodynia in both cephalic and hindpaw regions; cutaneous allodynia resolved to baseline levels after cessation of drug administration (14 days). Sumatriptan priming resulted in generalized and delayed cutaneous allodynia, evoked by either bright light stress (day 21) or nitric oxide donor (day 28). Ubrogepant dose-dependently blocked both stress- and nitric oxide donor-induced cephalic and hindpaw allodynia in the sumatriptan-induced medication overuse headache model with a 50% effective dose of ∼50 mg/kg. Unlike sumatriptan, ubrogepant 100 mg/kg in repeated effective doses did not produce cutaneous allodynia or latent sensitization. Conclusions Both ubrogepant and sumatriptan demonstrated efficacy as acute medications for stress- and nitric oxide donor-evoked cephalic allodynia in a preclinical model of medication overuse headache, consistent with their clinical efficacy in the acute treatment of migraine. However, in contrast to sumatriptan, repeated treatment with ubrogepant did not induce cutaneous allodynia or latent sensitization. These studies suggest ubrogepant may offer an effective acute treatment of migraine without risk of medication overuse headache. Trial Registration Number: Not applicable

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