Recurrent axon collaterals of intrinsically photosensitive retinal ganglion cells

Joo, Hannah R.; Peterson, Barry T.; Dacey, Dennis M.; Hattar, Samer; Chen, Shih‐Kuo

doi:10.1017/s0952523813000199

Cited by 71 publications

(63 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may suggest that other mechanisms than mTOR or Stat3 regulate the axon regeneration in M1 ipRGCs, because they can regenerate when presented with a peripheral graft (30). Interestingly, M1 ipRGCs have intraretinal axon collaterals that terminate in the inner plexiform layer of the retina (31). In dorsal root ganglion neurons, a surviving intact branch suppresses axon regeneration after a laser-induced lesion (32).…”

Section: Discussionmentioning

confidence: 99%

Promoting axon regeneration in the adult CNS by modulation of the melanopsin/GPCR signaling

Yang

Zhang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

111

109

View full text Add to dashboard Cite

Cell-type-specific G protein-coupled receptor (GPCR) signaling regulates distinct neuronal responses to various stimuli and is essential for axon guidance and targeting during development. However, its function in axonal regeneration in the mature CNS remains elusive. We found that subtypes of intrinsically photosensitive retinal ganglion cells (ipRGCs) in mice maintained high mammalian target of rapamycin (mTOR) levels after axotomy and that the light-sensitive GPCR melanopsin mediated this sustained expression. Melanopsin overexpression in the RGCs stimulated axonal regeneration after optic nerve crush by up-regulating mTOR complex 1 (mTORC1). The extent of the regeneration was comparable to that observed after phosphatase and tensin homolog (Pten) knockdown. Both the axon regeneration and mTOR activity that were enhanced by melanopsin required light stimulation and Gq/11 signaling. Specifically, activating Gq in RGCs elevated mTOR activation and promoted axonal regeneration. Melanopsin overexpression in RGCs enhanced the amplitude and duration of their light response, and silencing them with Kir2.1 significantly suppressed the increased mTOR signaling and axon regeneration that were induced by melanopsin. Thus, our results provide a strategy to promote axon regeneration after CNS injury by modulating neuronal activity through GPCR signaling.axon regeneration | neuronal activity | melanopsin | GPCR | mTOR S evered axons in the adult mammalian CNS do not spontaneously regenerate to restore lost functions. The failure of axons to regenerate is mainly attributed to the diminished growth capacity of neurons as well as an inhibitory environment (1-6). Optic nerves have been extensively studied for mechanisms regulating axon regeneration in CNS. When presented with permissive substrates such as a sciatic nerve graft, only axons of small populations of retinal ganglion cells (RGCs) regrow into the graft (7). When the intrinsic growth program is boosted, distinct subtypes of RGCs regenerate their axons (8). These findings indicate that the differential responses of RGCs to axotomy and growth stimulation are related to their intrinsic properties. One of the critical determinants of the intrinsic regenerative abilities of adult RGCs is neuronal mammalian target of rapamycin (mTOR) activity (9). In retinal axons, the loss of the potential to regrow is accompanied by down-regulation of mTOR activity in RGCs with maturation, and further reduction after axotomy. However, a small percentage of RGCs maintain high mTOR activation levels after optic nerve crush (9, 10). One can ask whether specific subsets of RGCs differ in their ability to maintain mTOR activation. Deciphering the physiological mechanism behind the mTOR maintenance could help elucidate the differential responses of neurons to injury signals and develop strategies to promote axon regeneration.Type 1 melanopsin expressing intrinsically photosensitive retinal ganglion cells (M1 ipRGCs) and αRGCs are resistant to axotomy-induced cell death (8, 11). M1 ipRGCs mainl...

show abstract

Section: Discussionmentioning

confidence: 99%

Promoting axon regeneration in the adult CNS by modulation of the melanopsin/GPCR signaling

Yang

Zhang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

111

109

View full text Add to dashboard Cite

show abstract

“…There is evidence suggesting a role of ipRGCs in the outer retinal photoreceptorsmediating image-forming functions via the intraretinal dopaminergic system (Joo et al, 2013;Prigge et al, 2016). The image-forming functions of ipRGCs are thought to be driven via the retrograde projection of the axons of ipRGC to the outer retina through the dopaminergic system (Joo et al, 2013;Prigge et al, 2016).…”

Section: Ambient Light and Depressionmentioning

confidence: 99%

“…The image-forming functions of ipRGCs are thought to be driven via the retrograde projection of the axons of ipRGC to the outer retina through the dopaminergic system (Joo et al, 2013;Prigge et al, 2016). The next section reviews the current literature on the image-forming retinal functions in depressive disorder.…”

Section: Ambient Light and Depressionmentioning

confidence: 99%

“…A small number of M1 ipRGCs (~ 10%) have been identified in the mouse retina that have axonal collaterals projecting back to the inner plexiform layer where they provide synaptic input to dopaminergic amacrine cells that are thought to be involved in the modulation of cone-driven light adaptation (Joo, Peterson, Dacey, Hattar, & Chen, 2013;Prigge, Yeh, Liou, Lee, You, Liu, McNeill, Chew, Hattar, Chen, & Zhang, 2016;Viney et al, 2007). The wild-type mice showed an increase in the b-wave of the light-adapted ERG amplitude while no change in the b-wave amplitude under similar condition was seen in the mice lacking M1 ipRGCs.…”

Section: Melanopsin-expressing Intrinsically Photosensitive Retinal Gmentioning

confidence: 99%

“…No study has, however, reported a direct measure of retinal dopamine in depression. M1 ipRGCs are believed to modulate cone adaptation via their retrograde axonal collaterals to the inner plexiform layer (IPL) where they synapse with the dopaminergic amacrine cells (Joo et al, 2013). Visual functions are partially controlled by retrograde signaling of ipRGCs to the outer retinal photoreceptors via the dopaminergic system in the retina (Prigge et al, 2016).…”

Section: Contrast Sensitivity (Cs)mentioning

confidence: 99%

See 2 more Smart Citations

An Evaluation of Melanopsin Function and Light Exposure in Depressive Disorders

Ojha¹

View full text Add to dashboard Cite

Aberrant light exposure causes depression in animals through a pathway involving the recently discovered intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). The photopigment melanopsin expressed in ipRGCs encodes irradiance to signal to the nonimage-forming centres of the brain, including the suprachiasmatic nucleus (SCN) for circadian photoentrainment and the olivary pretectal nucleus (OPN) to control the pupil light reflex. Mouse models have further identified ipRGC projections to the brain nuclei that regulate mood and behaviour. In humans, the post-illumination pupil response (PIPR), a sustained pupillary constriction after light offset, is used as a direct and non-invasive biomarker of ipRGC function.The PIPR amplitude is reduced in humans with seasonal affective disorder (SAD) that shows a seasonal variation in depressive episodes with a peak manifestation in winter when the solar light exposure is low, but a recent study including patients with non-seasonal depressive disorder did not detect ipRGC dysfunction. Moreover, neither study measured the ambient light exposure levels in patients with depression for comparison to healthy individuals without depression. The knowledge of the role of light coding cells (ipRGCs) in major depressive disorder (MDD) is incomplete unless the relationship between ambient light exposure levels and melanopsin function is evaluated. This study aims to measure the environmental light exposure levels and their relationship with melanopsin-mediated PIPR in non-seasonal depression. It is hypothesised that the patients with non-seasonal depression are exposed to low light levels and this is associated with impaired melanopsin function.A sample of 22 adults was recruited, including people with non-seasonal depression (n = 8, median age: 35 years) and healthy age-matched controls (n = 14, median age: 29 years).The presence of a DSM-IV MDD was assessed using the Mini International Neuropsychiatry ii Interview (MINI 6). The severity of depression symptoms was assessed with the Beck Depression Inventory (BDI-II). Individuals with recurrent MDD assessed with the MINI and a positive screen on the Seasonal Pattern Assessment Questionnaire and the Hamilton Depression Rating Scale-SAD (HDRS-SAD) were excluded as SAD. Both groups had visual acuity ≥ 6/6, normal colour vision and intraocular pressure (IOP) ≤ 21 mmHg, no corneal and lenticular opacities and normal retinae and optic discs. The ipRGC-mediated PIPR was measured using a short duration (1 s) high irradiance (15.5 log quanta.cm -2 .s -1 ) short wavelength (blue appearing) light stimulus with a custom built Maxwellian view pupillometer. Light exposure levels, sleep-wake times and sleep efficiency were determined over 2 weeks with an ambulatory light sensor device (Geneactive).The mean daily light exposure levels were similar between the groups and there were no statistically significant differences between the groups for light exposure levels as a function of clock hours, nor in the total number of minutes of exposu...

show abstract

Melanopsin‐expressing ganglion cells on macaque and human retinas form two morphologically distinct populations

Liao

Ren

Peterson

et al. 2016

J of Comparative Neurology

Self Cite

129

222

View full text Add to dashboard Cite

The long-term goal of this research is to understand how retinal ganglion cells that express the photopigment melanopsin, also known as OPN4, contribute to vision in humans and other primates. Here we report the results of anatomical studies using our polyclonal antibody specifically against human melanopsin that confirm and extend previous descriptions of melanopsin cells in primates. In macaque and human retina, two distinct populations of melanopsin cells were distinguished based on dendritic stratification in either the inner or outer portion of the inner plexiform layer (IPL) . Variation in dendritic field size and cell density with eccentricity was confirmed, and dendritic spines, a new feature of melanopsin cells, were described. The spines were the sites of input from DB6 diffuse bipolar cell axon terminals to the inner stratifying type of melanopsin cells. The outer stratifying melanopsin type received inputs from DB6 bipolar cells via the DB6 cell’s bistratified outer axonal processes. Outer stratifying melanopsin cells also received inputs from axon terminals of dopaminergic amacrine cells. On the outer stratifying melanopsin cells, ribbon synapses from bipolar cells and conventional synapses from amacrine cells were identified in electron-microscopic immunolabeling experiments. Both inner and outer stratifying melanopsin cell types were retrogradely labeled following tracer injection in the lateral geniculate nucleus (LGN). In addition, a method for targeting melanopsin cells for intracellular injection using their intrinsic fluorescence was developed. This technique was used to demonstrate that melanopsin cells were tracer-coupled to amacrine cells and would be applicable to electrophysiological experiments in the future.

show abstract

Recurrent axon collaterals of intrinsically photosensitive retinal ganglion cells

Cited by 71 publications

References 50 publications

Promoting axon regeneration in the adult CNS by modulation of the melanopsin/GPCR signaling

Promoting axon regeneration in the adult CNS by modulation of the melanopsin/GPCR signaling

An Evaluation of Melanopsin Function and Light Exposure in Depressive Disorders

Melanopsin‐expressing ganglion cells on macaque and human retinas form two morphologically distinct populations

Contact Info

Product

Resources

About