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)

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)

Bray ER, Noga M, Thakor K, Wang Y, Lemmon VP, Park KK, Tsoulfas P (2017) 3D visualization of individual regenerating retinal ganglion cell axons reveals surprisingly complex growth paths. eNeuro 4:ENEURO.0093-0017.2017. doi: 10.1523/ENEURO.0093-17.2017 PMID: 28856242

Summary: “Our study demonstrates extensive and circuitous RGC axon elongation both in pre- and post-lesion regions, highlighting the need to better understand the factors that inhibit direct axon growth in the optic nerve.”

Usage: Immunohistochemistry: Rabbit-anti-melanopsin (OPN4; UF006) 1:2500 (Cat. #AB-N38)

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

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 PMID: 28361990

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)

Somasundaram P, Wyrick G, Fernandez D, Ghahari A, Pinhal C, Simmonds Richardson M, Rupp A, Cui L, Wu Z, Brown R, Badea T, Hattar S, Robinson P (2017) C-terminal phosphorylation regulates the kinetics of a subset of melanopsin-mediated behaviors in mice. Proc Natl Acad Sci U S A 114:2741-2746. doi: 10.1073/pnas.1611893114 PMID: 28223508

Summary: The authors show that the melanopsin photoresponse shutoff due to C-terminal phosphorylation determines the kinetics of the intrinsic light response in ipRGCs, the PLR, and reentrainment, but not masking and phase angle of entrainment. Immunofluorescence was performed using rabbit Anti-Melanopsin (1:1,000, Cat. #AB-N38) as the primary antibody with a 2-d incubation period, followed by goat anti-rabbit IgG 488 as the secondary antibody.

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

Joly S, Lamoureux S, Pernet V (2017) Nonamyloidogenic processing of amyloid beta precursor protein is associated with retinal function improvement in aging male APP. Neurobiol Aging 53:181-191. doi: 10.1016/j.neurobiolaging.2017.02.004 PMID: 28262325

Objective: To determine amyloid beta role in the aging retina in Alzheimer’s Disease

Summary: Retinal-specific processing of amyloid may confer protection against AD and selectively preserve cone-dependent vision during aging.

Usage: Immunohistochemistry 1:1000

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

Ueki Y, Ramirez G, Salcedo E, Stabio ME, Lefcort F (2016) Loss of Ikbkap causes slow, progressive retinal degeneration in a mouse model of familial dysautonomia. eNeuro 3:ENEURO.0143-0116.2016. doi: 10.1523/eneuro.0143-16.2016 PMID: 27699209

Summary: Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that is caused by a mutation in the gene for inhibitor of kappa B kinase complex-associated protein (IKBKAP). A classic hallmark of the disease is progressive blindness marked by retinal ganglion cell (RGC) loss and optic nerve atrophy. To investigate the consequences of Ikbkap loss in the retina, we generated Ikbkap conditional knockout mice using TUBA1a-Cre. Our data demonstrate that this is a powerful model system that faithfully recapitulates the phenotype and progression of FD blindness.

Usage: Immunohistochemistry

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

Lim J, Stafford B, Nguyen P, Lien B, Wang C, Zukor K, He Z, Huberman A (2016) Neural activity promotes long-distance, target-specific regeneration of adult retinal axons. Nat Neurosci 19:1073-1084. doi: 10.1038/nn.4340 PMID: 27399843

Summary: Axons in the CNS fail to regenerate after injury. Scientists sought to identify strategies that would allow retinal ganglion cell (RGC) axons to regenerate in the eye-to-brain pathway, and if that was possible, whether the axons could reconnect with their correct targets and restore visual function. It was previously shown that increasing mTOR signaling could trigger RGC axon regeneration. Several conditions were tested, but combining increased mTOR signaling and then exposing mice to high-contrast visual stimulation daily for 3 weeks scientists after optic nerve crush resulted in long distance RGC axon regeneration, re-innervation of the brain and partial recovery of a subset of visual behaviors. A 1:1000 dilution of Anti-Melanopsin (Cat. #AB-N38) was used for the immunohistochemical analysis of retinas, optic nerves and brain tissue.

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

Arroyo D, Kirkby L, Feller M (2016) Retinal waves modulate an intraretinal circuit of intrinsically photosensitive retinal ganglion cells. J Neurosci 36:6892-6905. doi: 10.1523/JNEUROSCI.0572-16.2016 PMID: 27358448

Summary: The researchers explore the neural circuits underlying the ipRGC driven light responses of the developing retina and the mechanisms by which retinal waves regulate these circuits. They demonstrate that, even in the presence of cholinergic waves, ipRGC gap junction microcircuits propagate light-driven signals, thus strongly contributing to the overall light response of the developing retina. Following fixation, retinas were washed in PBS and remounted onto a new piece of filter paper. They were incubated in blocking buffer and then in primary immunoreaction solution, 1:2500 rabbit anti-melanopsin (Cat. #AB-N38). Results show that, during development, ipRGCs form extensive gap junction microcircuits that shape the early retinal light response. Retinal waves exert a far-reaching, neuromodulatory influence on these circuits via dopaminergic modulation of gap junctions, thus potentially impacting the processing of early visual input.

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)