Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice

Jakobs, Tatjana C.; Libby, Richard T.; Ben, Yixin; John, Simon W. M.; Masland, Richard H.

doi:10.1083/jcb.200506099

Cited by 345 publications

(390 citation statements)

References 45 publications

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“…This pattern is matched by pathologic process in the retina and optic nerve for both human glaucoma (33) and the DBA/2 mouse (8,14,24,25). The depletion of CTB transport from the retina to its primary projection site, the SC, follows a and aged (7-9 mo) rats is elevated acutely by 40% to 45% with microbead injection (circles) compared with saline solution in the opposite eye (diamonds).…”

Section: Discussionmentioning

confidence: 95%

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Distal axonopathy with structural persistence in glaucomatous neurodegeneration

Crish

Sappington

Inman

et al. 2010

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

316

482

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An early hallmark of neuronal degeneration is distal transport loss and axon pathology. Glaucoma involves the degeneration of retinal ganglion cell (RGC) neurons and their axons in the optic nerve. Here we show that, like other neurodegenerations, distal axon injury appears early in mouse glaucoma. Where RGC axons terminate in the superior colliculus, reduction of active transport follows a retinotopic pattern resembling glaucomatous vision loss. Like glaucoma, susceptibility to transport deficits increases with age and is not necessarily associated with elevated ocular pressure. Transport deficits progress distal-to-proximal, appearing in the colliculus first followed by more proximal secondary targets and then the optic tract. Transport persists through the optic nerve head before finally failing in the retina. Although axon degeneration also progresses distal-to-proximal, myelinated RGC axons and their presynaptic terminals persist in the colliculus well after transport fails. Thus, distal transport loss is predegenerative and may represent a therapeutic target.axon transport | optic neuropathy | retinal ganglion cell | glaucoma | optic nerve

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Section: Discussionmentioning

confidence: 95%

“…1 C and D resemble sectorial vision loss in glaucoma, which extends to the RGC-rich central retina (23). Some degenerative markers in the aged DBA/2 optic nerve and retina also have this pattern (8,14,24,25). The area around the optic disk in the rodent contains the highest RGC density, like the human central retina (26).…”

Section: Resultsmentioning

confidence: 99%

Distal axonopathy with structural persistence in glaucomatous neurodegeneration

Crish

Sappington

Inman

et al. 2010

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

316

482

View full text Add to dashboard Cite

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“…In a rat glaucoma model of chronic ocular hypertension induced by weekly injections of chondroitin sulfate into the anterior chamber, melanopsinexpressing RGCs were also found to be equally susceptible to the deleterious effects of ocular hypertension and functional deficits in irradiance responses were also described (de Zavalia et al 2011). In a model of inherited glaucoma (mouse strain DBA/2J) in which IOP is elevated, melanopsin-expressing RGCs are not selectively spared (Jakobs et al 2005). Patients with early-stage glaucoma show no deficits in ipRGC function determined by the postillumination pupil response whereas in people with advanced glaucoma, ipRGC function was reduced (Feigl et al 2011).…”

Section: Iprgcs and Retinal Diseasementioning

confidence: 99%

Intrinsically Photosensitive Retinal Ganglion Cells

Pickard

Sollars

2011

Reviews of Physiology, Biochemistry and Pharmacology 162

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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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“…Type specifi c degeneration has been noted in the primate (Weber et al, 1998 ), cat (Shou et al, 2003 ), mouse (Leung et al, 2011 ;Feng et al, 2013 ), and rat (Thanos, 1988 ) but not in DBA/2J (Jakobs et al, 2005 ) or thy1-YFP-H transgenic mice with experimental glaucoma (Kalesnykas et al, 2012 ). The Sholl plots in Fig.…”

Section: Discussionmentioning

confidence: 91%

A novel system for the classification of diseased retinal ganglion cells

et al. 2014

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Retinal ganglion cell (RGC) dendritic atrophy is an early feature of many forms of retinal degeneration, providing a challenge to RGC classifi cation. The characterization of these changes is complicated by the possibility that selective labeling of any particular class can confound the estimation of dendritic remodeling. To address this issue we have developed a novel, robust, and quantitative RGC classifi cation based on proximal dendritic features which are resistant to early degeneration. RGCs were labeled through the ballistic delivery of DiO and DiI coated tungsten particles to whole retinal explants of 20 adult Brown Norway rats. RGCs were grouped according to the Sun classifi cation system. A comprehensive set of primary and secondary dendrite features were quantifi ed and a new classifi cation model derived using principal component (PCA) and discriminant analyses, to estimate the likelihood that a cell belonged to any given class. One-hundred and thirty one imaged RGCs were analyzed; according to the Sun classifi cation, 24% ( n = 31) were RGC A , 29% ( n = 38) RGC B , 32% ( n = 42) RGC C , and 15% ( n = 20) RGC D . PCA gave a 3 component solution, separating RGCs based on descriptors of soma size and primary dendrite thickness, proximal dendritic fi eld size and dendritic tree asymmetry. The new variables correctly classifi ed 73.3% ( n = 74) of RGCs from a training sample and 63.3% ( n = 19) from a hold out sample indicating an effective model. Soma and proximal dendritic tree morphological features provide a useful surrogate measurement for the classifi cation of RGCs in disease. While a defi nitive classifi cation is not possible in every case, the technique provides a useful safeguard against sample bias where the normal criteria for cell classifi cation may not be reliable.

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Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice

Cited by 345 publications

References 45 publications

Distal axonopathy with structural persistence in glaucomatous neurodegeneration

Distal axonopathy with structural persistence in glaucomatous neurodegeneration

Intrinsically Photosensitive Retinal Ganglion Cells

A novel system for the classification of diseased retinal ganglion cells

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