14 entries found for : it-44
Ostrin LA, Strang CE, Chang K, Jnawali A, Hung L-F, Arumugam B, Frishman LJ, Smith EL, Gamlin PD (2018) Immunotoxin-induced ablation of the intrinsically photosensitive retinal ganglion cells in rhesus monkeys. Front Neurol 9:1000. doi: 10.3389/fneur.2018.01000Objective: To develop and validate a targeted ipRGC immunotoxin to ultimately examine the role of ipRGCs in macaque monkeys.
Summary: Findings demonstrated that Melanopsin-SAP was specific for ipRGCs, and induced a graded reduction in the PLR (pupillary light reflex), as well as in ipRGC-driven pupil response with concentration.
Usage: Solutions of 0.316, 1, 3.16, 10, and 50 μg delivered intravitreally.
Related Products: Melanopsin-SAP (Cat. #IT-44)
Garrett AM, Khalil A, Walton DO, Burgess RW (2018) DSCAM promotes self-avoidance in the developing mouse retina by masking the functions of cadherin superfamily members. Proc Natl Acad Sci U S A 115:E10216-E10224. doi: 10.1073/pnas.1809430115
Summary: Focus on DSCAM (Down syndrome cell adhesion molecule 1) self-avoidance function in the mouse retina. DSCAM and members of the cadherin superfamily have also emerged as key contributors to a variety of neurodevelopmental disorders, including autism, schizophrenia, bipolar disease, Down syndrome and intellectual disability.
Related Products: Melanopsin-SAP (Cat. #IT-44)
Potter H, Alenciks E, Frazier K, Porter A, Fraley GS (2018) Immunolesion of melanopsin neurons causes gonadal regression in Pekin drakes (Anas platyrhynchos domesticus). Gen Comp Endocrinol 256:16-22. doi: 10.1016/j.ygcen.2017.08.006Objective: Examine effects of loss of melanopsin in drakes.
Summary: Loss of melanopsin in PMM elicits decrease in GnRH mRNA expression, gonadal regression, and sex behaviors in drakes.
Usage: To specifically lesion melanopsin-receptive neurons, 3 μl of an anti-melanopsin-saporin conjugate (MSAP, 100 ng/ul) was injected into the lateral ventricle (n = 10). Control drakes were injected with 3 μl of equimolar unconjugated anti-melanopsin and saporin (SAP, n = 10).
Related Products: Melanopsin-SAP (Cat. #IT-44), Saporin (Cat. #PR-01)
Zhang J, Wang H, Wu S, Liu Q, Wang N (2017) Regulation of reentrainment function is dependent on a certain minimal number of intact functional iprgcs in rd mice. J Ophthalmol 2017:6804853.. doi: 10.1155/2017/6804853
Related Products: Melanopsin-SAP (Cat. #IT-44)
Behavioral effects following ablation of retinal ganglion cells in diurnal grass rats
Fogo G, Gall AJ (2017) Behavioral effects following ablation of retinal ganglion cells in diurnal grass rats. Neuroscience 2017 Abstracts 237.03 / HH34. Society for Neuroscience, Washington, DC.
Summary: Light influences behavior and physiology in mammals by entraining circadian rhythms and also through direct and acute inhibition or stimulation of activity, a process called masking. Although there has been substantial progress elucidating the mechanisms responsible for the workings of the circadian system in nocturnal species, less is known about the mechanisms that support the diurnal profile of activity of mammals, especially as they relate to the retina. We recently showed that the intergeniculate leaflet (IGL) is critical for the display of normal patterns of daily activity in diurnal grass rats (Arvicanthis niloticus). Specifically, IGL lesions reverse the activity patterns of these animals such that they became night-active; this occurred through their effects on both circadian mechanisms and masking. The IGL is a thalamic structure that receives direct inputs from the melanopsin containing intrinsically photosensitive retinal ganglion cells, known as ipRGCs. Our current approach takes advantage of a diurnal mammalian model, the Nile grass rat, to test the novel hypothesis that melanopsin is critical for the expression of diurnal behavior and physiology, and is involved in masking responses to light. We will achieve this goal by injecting the immunotoxin anti-melanopsin-saporin intraocularly in grass rats and examining behavior following this experimental manipulation. Animals will be placed in various lighting conditions, including 12:12 light-dark conditions, and will be given pulses of light to test for effects of masking. We predict that controls will exhibit more general activity during the day, consistent with a diurnal species, and will exhibit increased activity following acute pulses of light. We predict that animals with the melanopsin toxin in the retina will be out of phase with controls in behavior following acute pulses of light, similar to animals with IGL lesions. Altogether, we are building a model to understand the mechanisms underlying the normal display of diurnal behavior, and we hope to add to this knowledge by examining how melanopsin contributes to the display of diurnal behavior in grass rats.
Related Products: Melanopsin-SAP (Cat. #IT-44)
Bowrey HE, James MH, Mohammadkhani A, Omrani M, Kane G, Aston-Jones G (2017) Chemogenetic activation of a retinal circuit that activates locus coeruleus neurons prevents the development of light- deprivation induced depression-like behavior. Neuroscience 2017 Abstracts 244.02 / NN6. Society for Neuroscience, Washington, DC.
Summary: Introduction: Chronic light-deprivation induces a depressive-like phenotype via a locus coeruleus norepinephrine (LC-NE)- dependent mechanism (Gonzalez and Aston-Jones, 2008). Suprachiasmatic nucleus (SCN) provides indirect circadian input onto LC via dorsomedial hypothalamus (DMH) (Aston-Jones et al 2001). SCN is therefore in a key position to integrate light information with LC via the pathway: retina→SCN→DMH→LC. We refer to this pathway as the Photic Regulation of Arousal and Mood (PRAM) pathway. We tested the hypothesis that increasing PRAM pathway activity prevents darkness-induced depression-like behavior. Methods: Expt 1. Sprague Dawley rats received intraocular injections of excitatory hM3Dq DREADD (AAV2-hSyn-hM3D(Gq)- mCherry) control virus (AAV2-hSyn-EGFP) or no virus. Rats were placed in continuous darkness for 8 weeks, and those that received virus were concurrently subjected to daily intraperitoneal injections of clozapine-N-oxide (CNO; 2 mg/kg), the DREADD-activating ligand. Rats were then subjected to assays of mood (saccharin preference test, elevated plus maze and forced swim test) or vision (electroretinagram: ERG). LC tissue was stained for Poly ADP ribose polymerase (PARP, a marker of apoptosis) and tyrosine hydroxilase (TH). Expt 2. To determine the retinal cell-type responsible for depression-like behavior, intrinsically photosensitive retinal ganglion cells (ipRGCs) of animals raised in 12:12 light:dark conditions were ablated using a saporin (SAP) toxin that selectively eliminates melanopsin-expressing cells (Mel-SAP). Two control groups received intraocular injections of vehicle and were kept in either continuous darkness or in 12:12 light:dark conditions. Ten weeks later, rats were subjected to identical analyses as those in Expt 1. Results: Expt 1. ERG analysis showed that CNO-activation of retinal DREADDs increased RGC activity. Constant darkness induced a depression-like phenotype in control animals, which was prevented by daily activation of retinal DREADDs by CNO. Expt 2. Mel-SAP induced a depression-like phenotype in animals maintained in normal light-dark conditions. This was also associated with increased apoptosis in LC-NE cells as seen with PARP staining. Conclusion: Dysregulation of the PRAM pathway may induce neural damage in LC-NE neurons that is associated with a depressive behavioral phenotype. DREADD-induced activation of RGCs can prevent depression-like behaviors that normally occur in rats kept in chronic darkness. The PRAM pathway presents a novel circuit for the regulation of mood, and thus a possible new direction for the treatment of some forms of depression in humans.
Related Products: Melanopsin-SAP (Cat. #IT-44)
A retinoraphe projection regulates serotonergic activity and looming-evoked defensive behaviour.
Huang L, Yuan T, Tan M, Xi Y, Hu Y, Tao Q, Zhao Z, Zheng J, Han Y, Xu F, Luo M, Sollars P, Pu M, Pickard G, So K, Ren C (2017) A retinoraphe projection regulates serotonergic activity and looming-evoked defensive behaviour. Nat Commun 8:14908. doi: 10.1038/ncomms14908
Objective: To investigate how the dorsal raphe nucleus (DRN) and superior colliculus work in concert to extract and translate visual threats into defensive behavioural responses.
Summary: A dedicated population of RGCs signals rapidly approaching visual threats and their input to the DRN controls a serotonergic self-gating mechanism that regulates innate defensive responses.
Usage: Mice received bilateral intraocular injection (2 μg per eye) made between Streptavidin-Saporin and a biotinylated CTB antibody, or Anti-Melanopsin-SAP (2 μg per eye). For detection of melanopsin, retinas were incubated for 3 days at 4 °C with anti-melanopsin (1:600).
Related Products: Streptavidin-ZAP (Cat. #IT-27), Melanopsin-SAP (Cat. #IT-44), Melanopsin Rabbit Polyclonal (Cat. #AB-N38)
Alenciks E, Frazier K, Porter A, Fraley G (2015) Immunolesions of melanopsin receptive neurons attenuates the hormonal reproductive axis in the adult but has no effect on growth in immature Peking ducks. Neuroscience 2015 Abstracts 613.05/R20. Society for Neuroscience, Chicago IL.
Summary: Several light sensitive receptors have been described in the avian brain that are thought to regulate the reproductive axis independently from the eyes and pineal gland. Recently, our lab has described the presence of 3 photoneuroendocrine systems in the Pekin duck: rhodopsin, opsin 5, & melanopsin. We set out to test the hypothesis that melanopsin receptive neurons are necessary to maintain seasonal reproductive status along with growth and development in the Pekin drake. To accomplish these goals we first investigated 50-week-old Pekin drakes that were housed in the aviary at Hope College under long day length (18 hrs lights on) conditions in floor pens. To specifically lesion melanopsin-receptive neurons, 3 μl of an anti-melanopsin-saporin conjugate (MSAP, 100 ng/ul) was injected into the lateral ventricle (n = 10). Control drakes were injected with 3 ul of equimolar unconjugated anti-melanopsin and saporin (SAP, n = 10). The drakes were returned to the aviary after complete recovery. Reproductive behaviors were analyzed weekly in a test pen with adult hens. After 4 weeks, birds were euthanized and body weights were measured, and brains, pituitaries, and testes collected and stored for analyses. To test melanopsin’s effect on immature ducks the same surgery was performed on a group of 10 day old ducks (n= 10). Ducks were weighed weekly starting at 3 days of age. After a final weight was obtained at 50 days of age, ducks were euthanized and a blood sample was collected and sent out for an avian panel. Mature MSAP-treated drakes had significantly (p< 0.001) reduced relative teste weights compared to SAP controls. qRT-PCR analyses (n= 3 per treatment) of anterior pituitary showed a significant reduction (p< 0.001) in both LH-beta and FSH mRNA’s. Immunoctyochemical analyses (n= 3 per treatment) showed a significant reduction in melanopsin and GnRH-immunoreactivities. Immature drake BW did not differ significantly between MSAP and SAP animals at any of the measured days. The data appeared to drift toward significance near the end of the sampling period (p = 0.297). Blood panel results revealed no significant differences between MSAP and SAP animals in any CBC component. Serum glutamic-oxaloacetic transaminase (SGOT) (p= 0.022) and creatine phosphokinase (CPK) values were significantly elevated (p = 0.006) in MSAP animals compared to controls. Although melanopsin neurons in the PMM appear to have an important role in adult drakes, their importance in the growth of immature ducks is still unclear. However, these data underscore the importance of the photoneuroendocrine system in maintaining the reproductive axis along with growth and development in seasonally breeding birds.
Related Products: Melanopsin-SAP (Cat. #IT-44), Saporin (Cat. #PR-01)
Fraley GS (2014) Immunolesions of melanopsin receptive neurons in the adult Pekin drake attenuates the hormonal reproductive axis. Neuroscience 2014 Abstracts 543.01. Society for Neuroscience, Washington, DC.
Summary: Several light sensitive receptors have been described in the avian brain that are thought to regulate the reproductive axis independently from the eyes and pineal gland. Recently, my lab has described the presence of three of these photoneuroendocrine systems in the Pekin duck: opsin, opsin 5, and melanopsin. I set out to test the hypothesis that melanopsin receptive neurons are necessary to maintain seasonal reproductive status in the Pekin drake. To accomplish this, 50-week-old Pekin drakes were housed in the aviary at Hope College under long day length (18 hrs lights on) conditions in floor pens (5 drakes per pen). To specifically lesion melanopsin-receptive neurons, drakes were anethestized (8 mg/kg Propofol, IV), given analgesics (2 mg/kg ketfen, SC) skin incised and a trephine hole drilled 10 mm caudal to bony orbits and 1 mm to the left of midline. A 33 gauge stainless steel needle attached to a Hamilton syringe was lowered stereotactically 3.5 mm ventral to dura into the lateral ventricle. Three microliters of an anti-melanopsin-saporin conjugate (MSAP, 100 ng/ul) was injected into the lateral ventricle (n = 10). Control drakes were injected with 3 ul of equimolar unconjugated anti-melanopsin and saporin (SAP, n = 10). The incision was closed with VetBond, and the drakes returned to the aviary after complete recovery from anesthesia. After 4 weeks, birds were euthanized (400 mg/kg FatalPlus, IP) and body weight measured, and brains, pituitaries, and testes collected and stored for analyses. MSAP-treated drakes had significantly (p < 0.001) reduced relative teste weights compared to SAP controls. qRT-PCR analyses (n = 5 per treatment) of anterior pituitary showed a significant reduction (p < 0.001) in both LH-beta and FSH mRNA’s. Immunoctyochemical analyses (n = 5 per treatment) showed a significant reduction in melanopsin and GnRH-immunoreactivities. These data underscore the importance of the photoneuroendocrine system in maintaining the reproductive axis in seasonally breeding birds.
Related Products: Melanopsin-SAP (Cat. #IT-44)
Direct retino-raphe projection alters serotonergic tone and affective behavior.
Ren C, Luan L, Wui-Man Lau B, Huang X, Yang J, Zhou Y, Wu X, Gao J, Pickard GE, So KF, Pu M (2013) Direct retino-raphe projection alters serotonergic tone and affective behavior. Neuropsychopharmacology 38(7):1163-1175. doi: 10.1038/npp.2013.35
Summary: Although recent work has shown that some intrinsically photosensitive retinal ganglion cells (ipRGCs) are responsible for processing nonimage-forming visual functions, it is unclear whether the ipRGCs or conventional RGCs modulate affective behavior. The authors injected 2 μg of melanopsin-SAP (Cat. #IT-44) into each eye of gerbils, or biotinylated CTB monoclonal antibody coupled to Streptavidin-ZAP (Cat. #IT-27). The data suggest that retino-raphe signals modulate dorsal raphe nucleus serotonergic tone and affective behavior.
Related Products: Melanopsin-SAP (Cat. #IT-44), Streptavidin-ZAP (Cat. #IT-27)
Van Der List DA, Chapman B (2011) Targeted ablation of intrinsically photosensitive melanopsin expressing retinal ganglion cells early in development alters retinal morphology within the inner plexiform layer of mice. Neuroscience 2011 Abstracts 232.12. Society for Neuroscience, Washington, DC.
Summary: It has been demonstrated in adult mice, that eliminating a small subset of retinal ganglion cells expressing the photopigment melanopsin (ip-RGCs) with an immunotoxin alters the effects of light on circadian rhythms. The immunotoxin was made by conjugating the melanopsin antibody with ribosome-inactivating protein, saporin. It has also been observed that the ablation of ip-RGCs in adult mice did not alter retinal morphology. Specifically, it was found that dendrites arising from starburst amacrine cells retained their position within the inner plexiform layer (IPL) suggesting no reorganization within this synaptic layer (Goz et al. 2008). In this study, we used the same melanopsin immunotoxin (Mx) (Advanced Targeting Systems) to perform intravitreal injections into mice at postnatal day one. The animals were sacrificed at P26 and the retina fixed in 4%PFA, frozen transverse sections were then immunostained with antibodies against melanopsin, choline acetyl transferase (ChAT), calreinin, calbindin, PKC and Kv4.2. In control retinae, melanosin antibody stained ip-RGC cell bodies and dendrites stratifying in both On and Off layers of the IPL, whereas retinae treated with Mx shows a loss of melanopsin-containing cell bodies and dendrites. In control retinae, ChAT stains starburst amacrine cells with cell bodies in the RGC and INL layers and two distinct bands in the IPL. In Mx treated retinae, most starburst amacrine cells appear to be eliminated along with melanopsin RGCs. Interestingly, if there is a hint of residual melanopsin expressing dendrites remaining, there is also a ChAT expressing cell body and a hint of dendrites in the synaptic layer. In control retinae, calretinin and calbindin antibodies stain a subset of RGCs and amacrine cells and show a characteristic three-layered pattern of dendrites in the IPL. In Mx treated retinae, the calretinin and calbindin layers within the IPL are altered showing an absent or more diffuse labeling pattern in the ON and OFF bands. Antibodies against PKC (staining rod bipolar cells) and Kv4.2 (stains a subset of retinal ganglion cells) do not show an altered staining pattern. These findings suggest that the initial stratification and structural development of synaptic layers in the IPL are altered by Mx treatment.
Related Products: Melanopsin-SAP (Cat. #IT-44)
Intrinsically photosensitive retinal ganglion cells.
Do MTH, Yau K (2010) Intrinsically photosensitive retinal ganglion cells. Physiol Rev 90(4):1547-1581. doi: 10.1152/physrev.00013.2010
Summary: This review presents recent data that has established the importance of intrinsically photosensitive retinal ganglion cells (ipRPG) in nonimage visual functions. The use of melanopsin-SAP (Cat. #IT-44) in both mice and rats is discussed. It is of note that depletion of ipRPG's using melanopsin-SAP resulted in deficits in communication to nonimage regions of the brain, but image vision appeared normal.
Related Products: Melanopsin-SAP (Cat. #IT-44)
Immunotoxin-induced ablation of melanopsin retinal ganglion cells in a non-murine mammalian model.
Ingham ES, Gunhan E, Fuller PM, Fuller CA (2009) Immunotoxin-induced ablation of melanopsin retinal ganglion cells in a non-murine mammalian model. J Comp Neurol 516:125-140. doi: 10.1002/cne.22103
Related Products: Melanopsin-SAP (Cat. #IT-44)
Göz D, Studholme K, Lappi DA, Rollag MD, Provencio I, Morin LP (2008) Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms. PLoS ONE 3(9):e3153. doi: 10.1371/journal.pone.0003153
Summary: Retinal ganglion cells expressing melanopsin photopigment are thought to be involved in non-image forming visual responses to light. The authors had a custom conjugate made between saporin and an anti-melanopsin antibody. A 400-ng injection of the melanopsin-SAP conjugate into the eye of a mouse resulted in a 57% loss of the targeted cells. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The data indicates that melanopsin-containing cells are involved in the response to certain non-image forming visual input.
Related Products: Melanopsin-SAP (Cat. #IT-44), Melanopsin Rabbit Polyclonal (Cat. #AB-N38), Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39), Rabbit IgG-SAP (Cat. #IT-35)