Melanopsin-Expressing Retinal Ganglion Cells Are More Injury-Resistant in a Chronic Ocular Hypertension Model

Li, Rachel S.; Chen, Bai Yu; Tay, David; Chan, Ho Lung Henry; Pu, Ming Liang; So, Kwok-Fai

doi:10.1167/iovs.05-1295

Cited by 131 publications

(128 citation statements)

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“…Following that, although the difference is insignificant, the loss of mRGCs were found to be proportionally less than the total number of RGCs in DBA/2 J mice with severe glaucoma damage (Jakobs et al 2005). Recently, mRGCs are also shown to be less vulnerable to the injury of OH in rats (Li et al 2006a). In the present study, our data confirm that mRGCs were relatively less susceptible to optic nerve injury and OH.…”

Section: Discussionmentioning

confidence: 96%

“…Our recently published study demonstrated that cells expressing melanopsin are less susceptible to damage under the condition of elevated IOP (Li et al 2006a). In the present study, our result again confirmed that there was no significant loss of mRGCs after the (Figs.…”

Section: Effect Of Pi3 K/akt Inhibitors On Mrgc Survival After Injurymentioning

confidence: 99%

“…The mRGCs were visualized by using the immunohistochemical procedures published previously (Li et al 2006a). Retinas were washed and blocked with 10% normal goat serum in 0.3% Triton X-100 and PBS mixture (PBT) for an hour at room temperature.…”

Section: Tissue Processing and Immunohistochemistry Of Mrgcsmentioning

confidence: 99%

“…Following that, our group found that mRGCs survive relatively longer in the ocular hypertension (OH) model, whereas a significant number of superior colliculusprojecting RGCs (scRGCs) die in the process (Li et al 2006a). The resistance to injury may be probably due to the extensively branched dendrites and the unique intrinsic properties of melanopsin.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Survival of Melanopsin-expressing Retinal Ganglion Cells After Injury is Associated with the PI3 K/Akt Pathway

Yau

Chen

et al. 2008

Cell Mol Neurobiol

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In the present study, we studied the factors that contribute to the injury-resistant property of melanopsin-expressing retinal ganglion cells (mRGCs). Since phosphatidylinositol-3 kinase (PI3 K)/Akt signaling pathway is one of the well-known pathways for neuronal cell survival, we investigated the survival of mRGCs by applying the PI3 K/Akt specific inhibitors after injury. Two injury models, unilateral optic nerve transection and ocular hypertension, were adopted using Sprague-Dawley rats. Inhibitors of PI3 K/Akt were injected intravitreally following injuries to inhibit the PI3 K/Akt signaling pathway. Retinas were dissected after designated survival time, immunohistochemistry was carried out to visualize the mRGCs using melanopsin antibody and the number of mRGCs was counted. Co-expression of melanopsin and phospho-Akt (pAkt) was also examined. Compared to the survival of non-melanopsin-expressing RGCs, mRGCs showed a marked resistance to injury and co-expressed pAkt. Application of PI3 K/Akt inhibitors decreased the survival of mRGCs after injury. Our previous study has shown that mRGC are less susceptible to injury following the induction of ocular hypertension. In this study, we report that mRGCs were injury-resistant to a more severe type of injury, the optic nerve transection. More importantly, the PI3 K/Akt pathway was found to play a role in maintaining the survival of mRGCs after injury.

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Section: Discussionmentioning

confidence: 96%

Section: Effect Of Pi3 K/akt Inhibitors On Mrgc Survival After Injurymentioning

confidence: 99%

Section: Tissue Processing and Immunohistochemistry Of Mrgcsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enhanced Survival of Melanopsin-expressing Retinal Ganglion Cells After Injury is Associated with the PI3 K/Akt Pathway

Yau

Chen

et al. 2008

Cell Mol Neurobiol

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“…Several different animal models of glaucoma have been investigated to determine if melanopsin RGCs are injury-resistant. Melanopsin-expressing RGCs were found to be selectively spared compared to conventional RGCs in a rat model of chronic ocular hypertension induced by laser photocoagulation of the episcleral and limbal veins P h y s i o l B i o c h e m P h a R m a c o l 1 6 2 ( 2 0 1 2 ) of the eye with resultant elevated intraocular pressure (IOP) (Li et al 2006(Li et al , 2008. In a different rat model of episcleral vein cauterization, melanopsin-expression RGCs were not apparently spared (Drouyer et al 2008;Wang et al 2008) and functional deficits in irradiance responses were reported (Drouyer et al 2008).…”

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confidence: 99%

Intrinsically photosensitive retinal ganglion cells

Pickard

Sollars

2010

Sci. China Life Sci.

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Intrinsically photosensitive retinal ganglion cells (ipRGCs) respond to light in the absence of all rod and cone photoreceptor input. The existence of these ganglion cell photoreceptors, although predicted from observations scattered over many decades, was not established until it was shown that a novel photopigment, melanopsin, was expressed in retinal ganglion cells of rodents and primates. Phototransduction in mammalian ipRGCs more closely resembles that of invertebrate than vertebrate photoreceptors and appears to be mediated by transient receptor potential channels. In the retina, ipRGCs provide excitatory drive to dopaminergic amacrine cells and ipRGCs are coupled to GABAergic amacrine cells via gap junctions. Several subtypes of ipRGC have been identified in rodents based on their morphology, physiology and expression of molecular markers. ipRGCs convey irradiance information centrally via the optic nerve to influence several functions including photoentrainment of the biological clock located in the hypothalamus, the pupillary light reflex, sleep and perhaps some aspects of vision. In addition, ipRGCs may also contribute irradiance signals that interface directly with the autonomic nervous system to regulate rhythmic gene activity in major organs of the body. Here we review the early work that provided the motivation for searching for a new mammalian photoreceptor, the ground-breaking discoveries, current progress that continues to reveal the unusual properties of these neuron photoreceptors, and directions for future investigation.Keywords: Melanopsin, Circadian rhythms, Suprachiasmatic nucleus, Retina digitalcommons.unl.edu P i c k a r d & S o l l a r S i n R e v P h y s i o l B i o c h e m P h a R m a c o l1 6 2 ( 2 0 1 2 ) Early Hints of a Third Photoreceptor in the Mammalian RetinaThe perception of shapes, color and objects moving in the world begins in the outer retina where light is absorbed by photopigments that are integral membrane apoproteins (opsins) covalently linked to a retinaldehyde chromophore in the rod and cone photoreceptors. The capturing of photons by rod and cone photoreceptors initiates a signaling cascade in which photon capture is converted into an electrical signal. The simplest common pathway these signals take from the eye to the brain is from the photoreceptors to bipolar cells to ganglion cells. Retinal ganglion cells (RGCs) convey the signals centrally as action potentials, transmitted via their axons in the optic nerve, to higher brain regions for integration and the further processing required for conscious visual perception (Fig. 1). Among non-mammalian vertebrates, photoreceptors are also found in locations outside the retina, including the pineal gland and in the brain itself. These extra-ocular photoreceptors mediate tasks not associated directly with visual perception (non-image forming functions such as hormone regulation). However, since the pioneering descriptions of the vertebrate retina by Santiago Ramón y Cajal in the late 1800s, it was believed that t...

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Device erosion

Carroll

2009

Cathet Cardio Intervent

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Melanopsin-Expressing Retinal Ganglion Cells Are More Injury-Resistant in a Chronic Ocular Hypertension Model

Cited by 131 publications

References 40 publications

Enhanced Survival of Melanopsin-expressing Retinal Ganglion Cells After Injury is Associated with the PI3 K/Akt Pathway

Enhanced Survival of Melanopsin-expressing Retinal Ganglion Cells After Injury is Associated with the PI3 K/Akt Pathway

Intrinsically photosensitive retinal ganglion cells

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