Prolonged Melanopsin-based Photoresponses Depend in Part on RPE65 and Cellular Retinaldehyde-binding Protein (CRALBP)

Harrison, Krystal R.; Reifler, Aaron N.; Chervenak, Andrew P.; Wong, Kwoon Y.

doi:10.1080/02713683.2020.1815793

Cited by 8 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Melapts binding to melanopsin could directly or indirectly modify the structure of the domain in melanopsin that binds to the retinal, altering the phase shifts. Melanopsin loses its photosensitivity when its structure, function, and retinoid cycle are altered ( Dua et al, 2011 ; Harrison et al, 2021 ). For example, cis- retinal is present in cells bound to melanopsin without post-stimulation, which mediates photostimulation signal transduction into cells, as Melapts bound to melanopsin may influence intracellular signaling and phase shifts without photostimulation.…”

Section: Discussionmentioning

confidence: 99%

Melanopsin DNA aptamers can regulate input signals of mammalian circadian rhythms by altering the phase of the molecular clock

Nakazawa,

Matsuo,

Kikuchi

et al. 2024

Front. Neurosci.

View full text Add to dashboard Cite

DNA aptamers can bind specifically to biomolecules to modify their function, potentially making them ideal oligonucleotide therapeutics. Herein, we screened for DNA aptamer of melanopsin (OPN4), a blue-light photopigment in the retina, which plays a key role using light signals to reset the phase of circadian rhythms in the central clock. Firstly, 15 DNA aptamers of melanopsin (Melapts) were identified following eight rounds of Cell-SELEX using cells expressing melanopsin on the cell membrane. Subsequent functional analysis of each Melapt was performed in a fibroblast cell line stably expressing both Period2:ELuc and melanopsin by determining the degree to which they reset the phase of mammalian circadian rhythms in response to blue-light stimulation. Period2 rhythmic expression over a 24-h period was monitored in Period2:ELuc stable cell line fibroblasts expressing melanopsin. At subjective dawn, four Melapts were observed to advance phase by >1.5 h, while seven Melapts delayed phase by >2 h. Some Melapts caused a phase shift of approximately 2 h, even in the absence of photostimulation, presumably because Melapts can only partially affect input signaling for phase shift. Additionally, some Melaps were able to induce phase shifts in Per1::luc transgenic (Tg) mice, suggesting that these DNA aptamers may have the capacity to affect melanopsin in vivo. In summary, Melapts can successfully regulate the input signal and shifting phase (both phase advance and phase delay) of mammalian circadian rhythms in vitro and in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Melanopsin DNA aptamers can regulate input signals of mammalian circadian rhythms by altering the phase of the molecular clock

Nakazawa,

Matsuo,

Kikuchi

et al. 2024

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The higher steadystate spike rate should augment ipRGCs' ability to signal irradiance. Thus, ipRGC-AC coupling adds to the list of diverse mechanisms that promote tonic and long-lasting photoresponses in ipRGCs (Emanuel & Do, 2015;Mure et al, 2016;Zhao et al, 2016;Zhao et al, 2017a;Harrison et al, 2021b). Light-evoked ipRGC transmission to the coupled ACs could activate excitatory voltage-gated channels in the latter, which then signal back to the ipRGCs via gap junctions to help sustain the photoresponse.…”

Section: Discussionmentioning

confidence: 99%

“…8A) and have lower final-to-peak response ratios (P = 0.0349; Fig. 8C), a measure of photoresponse sustainedness (Zhao et al, 2016;Zhao et al, 2017a;Harrison et al, 2021b).…”

Section: Modulation Of Iprgcs' Intrinsic Photoresponsementioning

confidence: 99%

“…Considering the above potential caveats of two-photon imaging and Creþ photoreceptors, we again used MEAs to measure photoresponses during rod/cone signaling block, and we again tested 14.7 log quanta/cm 2 /s stimulus intensity so that all cells would spike throughout a 60 s step. We kept the stimulus duration so short because ipRGCs depend partly on the pigment epithelium to sustain their intrinsic photoresponse for longer than several minutes (Zhao et al, 2016), and at the time of these recordings we had not yet developed a mouse retinal preparation preserving connectivity with the epithelium (Harrison et al, 2021b). We recorded from 24 Opn4 Cre/þ ipRGCs and 34 Opn4 Cre/þ ; Cx36 flox/flox ipRGCs, and Fig.…”

Section: Modulation Of Iprgcs' Intrinsic Photoresponsementioning

confidence: 99%

See 1 more Smart Citation

Structure and function of the gap junctional network of photoreceptive ganglion cells

Zhao

Wong

2021

Vis Neurosci

Self Cite

View full text Add to dashboard Cite

Intrinsically photosensitive retinal ganglion cells (ipRGCs) signal not only anterogradely to drive behavioral responses, but also retrogradely to some amacrine interneurons to modulate retinal physiology. We previously found that all displaced amacrine cells with spiking, tonic excitatory photoresponses receive gap-junction input from ipRGCs, but the connectivity patterns and functional roles of ipRGC-amacrine coupling remained largely unknown. Here, we injected PoPro1 fluorescent tracer into all six types of mouse ipRGCs to identify coupled amacrine cells, and analyzed the latter’s morphological and electrophysiological properties. We also examined how genetically disrupting ipRGC-amacrine coupling affected ipRGC photoresponses. Results showed that ipRGCs couple with not just ON- and ON/OFF-stratified amacrine cells in the ganglion-cell layer as previously reported, but also OFF-stratified amacrine cells in both ganglion-cell and inner nuclear layers. M1- and M3-type ipRGCs couple mainly with ON/OFF-stratified amacrine cells, whereas the other ipRGC types couple almost exclusively with ON-stratified ones. ipRGCs transmit melanopsin-based light responses to at least 93% of the coupled amacrine cells. Some of the ON-stratifying ipRGC-coupled amacrine cells exhibit transient hyperpolarizing light responses. We detected bidirectional electrical transmission between an ipRGC and a coupled amacrine cell, although transmission was asymmetric for this particular cell pair, favoring the ipRGC-to-amacrine direction. We also observed electrical transmission between two amacrine cells coupled to the same ipRGC. In both scenarios of coupling, the coupled cells often spiked synchronously. While ipRGC-amacrine coupling somewhat reduces the peak firing rates of ipRGCs’ intrinsic melanopsin-based photoresponses, it renders these responses more sustained and longer-lasting. In summary, ipRGCs’ gap junctional network involves more amacrine cell types and plays more roles than previously appreciated.

show abstract

“…Additionally, CRABLP may play a critical role in chromophore transportation from RPCs to intrinsically photosensitive RGCs (ipRGCs), which are a subset of RGCs with the unique ability to directly sense light themselves. They are involved in visual image formation [152]. OPN4 is a typical gene marker for ipRGCs, and encodes for the protein melanopsin, which is a photopigment primarily expressed in ipRGCs and is essential for light-sensing functions [153].…”

Section: Molecular Markers For Evaluating Retinal Ganglion Cell Diffe...mentioning

confidence: 99%

Establishing Functional Retina in a Dish: Progress and Promises of Induced Pluripotent Stem Cell-Based Retinal Neuron Differentiation

Wong,

Yip,

Huang

2023

IJMS

View full text Add to dashboard Cite

The human eye plays a critical role in vision perception, but various retinal degenerative diseases such as retinitis pigmentosa (RP), glaucoma, and age-related macular degeneration (AMD) can lead to vision loss or blindness. Although progress has been made in understanding retinal development and in clinical research, current treatments remain inadequate for curing or reversing these degenerative conditions. Animal models have limited relevance to humans, and obtaining human eye tissue samples is challenging due to ethical and legal considerations. Consequently, researchers have turned to stem cell-based approaches, specifically induced pluripotent stem cells (iPSCs), to generate distinct retinal cell populations and develop cell replacement therapies. iPSCs offer a novel platform for studying the key stages of human retinogenesis and disease-specific mechanisms. Stem cell technology has facilitated the production of diverse retinal cell types, including retinal ganglion cells (RGCs) and photoreceptors, and the development of retinal organoids has emerged as a valuable in vitro tool for investigating retinal neuron differentiation and modeling retinal diseases. This review focuses on the protocols, culture conditions, and techniques employed in differentiating retinal neurons from iPSCs. Furthermore, it emphasizes the significance of molecular and functional validation of the differentiated cells.

show abstract

Prolonged Melanopsin-based Photoresponses Depend in Part on RPE65 and Cellular Retinaldehyde-binding Protein (CRALBP)

Cited by 8 publications

References 43 publications

Melanopsin DNA aptamers can regulate input signals of mammalian circadian rhythms by altering the phase of the molecular clock

Melanopsin DNA aptamers can regulate input signals of mammalian circadian rhythms by altering the phase of the molecular clock

Structure and function of the gap junctional network of photoreceptive ganglion cells

Establishing Functional Retina in a Dish: Progress and Promises of Induced Pluripotent Stem Cell-Based Retinal Neuron Differentiation

Contact Info

Product

Resources

About