Retrograde Signaling in the Optic Nerve Is Necessary for Electrical Responsiveness of Retinal Ganglion Cells

Chou, Tsung Han; Park, Kevin K.; Luo, Xueting; Porciatti, Vittorio

doi:10.1167/iovs.12-11188

Cited by 45 publications

(43 citation statements)

References 61 publications

(69 reference statements)

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“…6 The RGC counts showed massive (>85%) RGC loss in the operated eyes. Figure 3 of the study of Chou et al 6 shows that 1 month after ONC, the corneal PERG was dramatically reduced compared to the intact eye together with a major depletion of the RGC population, whereas Figure 4 of that study shows that the FERG was comparable in the two eyes. Figure 5 of the present study shows LED/snout PERGs derived from the right eyes of the 3 mice reported in the study of Chou et al 6 before and 1 month after ONC.…”

Section: Validitymentioning

confidence: 92%

“…As a control that the snout PERG reflected RGC activity as the corneal PERG, we used unpublished data on binocular snout PERG recorded in parallel with corneal PERG from a recent study of Chou et al 6 In that study, corneal PERGs and photopic FERGs were recorded in 3 C57BL/6J mice before and 1 month after unilateral, intraorbital optic nerve crush (ONC). 6 The RGC counts showed massive (>85%) RGC loss in the operated eyes.…”

Section: Validitymentioning

confidence: 99%

“…4,[10][11][12][13][14][15][16][17][18][19] Concurrently, studies have been conducted in mouse models to understand better the biological basis of the PERG signal. [4][5][6]20,21 Recently, Chou and Porciatti 21 reported that the bioelectrical field associated with the generation of the PERG signal in the mouse drastically differs from the bioelectrical field associated with the generation of the flash ERG. 22 The PERG bioelectric field is consistent with a dipole model whose axis is predominantly orthogonal to the eye axis, whereas the standard dipole model for the flash ERG (FERG) is coaxial.…”

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confidence: 99%

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Robust Mouse Pattern Electroretinograms Derived Simultaneously From Each Eye Using a Common Snout Electrode

Chou

Bohórquez

Toft-Nielsen

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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The PERG, a sensitive measure of RGC function, is used increasingly in mouse models of glaucoma and optic nerve disease. Compared to current methods, the binocular snout PERG represents a substantial improvement in terms of simplicity and speed. It also overcomes limitations of corneal electrodes that interfere with invasive procedures of the eye and facilitates experiments based on comparison between the responses of the two eyes.

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Section: Validitymentioning

confidence: 92%

Section: Validitymentioning

confidence: 99%

mentioning

confidence: 99%

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Robust Mouse Pattern Electroretinograms Derived Simultaneously From Each Eye Using a Common Snout Electrode

Chou

Bohórquez

Toft-Nielsen

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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“…Retinal ganglion cell function was assessed by means of the PERG, an electrical signal that specifically depends on RGC integrity [32][33][34] and is commonly used in human and experimental models of glaucoma and optic neuropathies. [35][36][37] Pattern electroretinograms were simultaneously recorded from both eyes according to a new paradigm recently described.…”

Section: Pattern Electroretinogrammentioning

confidence: 99%

“…Axonopathy at the junction between the retina and optic nerve is of particular interest, as it is believed to be the point of origin of glaucomatous neuropathy in humans 53 and mice. 35,54,55 As the PERG signal is also believed to be mainly generated by optic nerve axons in the optic nerve head, 33 axonopathy and astrocytic activation at this level may substantially impair the response.…”

Section: Tyr437his Mutant Of Human Myocilin Protein and Rgc Functionmentioning

confidence: 99%

Transgenic Mice Expressing Mutated Tyr437His Human Myocilin Develop Progressive Loss of Retinal Ganglion Cell Electrical Responsiveness and Axonopathy With Normal IOP

Chou

Tomarev

Porciatti

2014

Invest. Ophthalmol. Vis. Sci.

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Citation: Chou T-H, Tomarev S, Porciatti V. Transgenic mice expressing mutated Tyr437His human myocilin develop progressive loss of retinal ganglion cell electrical responsiveness and axonopathy with normal IOP. Invest Ophthalmol Vis Sci. 2014;55:5602-5609. DOI:10.1167/ iovs.14-14793 PURPOSE. To characterize age-related changes of retinal ganglion cell (RGC) function, IOP, and anatomical markers of axon/glia integrity in a transgenic mouse expressing Tyr437His mutant of human myocilin protein. METHODS.Retinal ganglion cell electrical responsiveness was tested with pattern electroretinogram (PERG) in 11 transgenic mice expressing mutated myocilin at different ages over 18 months under ketamine/xylazine anesthesia. Twelve age-matched C57BL/6J mice also were tested as controls. Intraocular pressure was measured with a Tonolab tonometer. Immunohistochemistry for GFAP and neurofilament was performed on dissected optic nerve heads.RESULTS. In transgenic mice expressing mutated myocilin, the PERG amplitude progressively decreased with increasing age by approximately 50%, whereas the PERG peak latency increased by approximately 40 ms (ANOVA, P < 0.05). In contrast, PERGs of young and old control mice had similar amplitudes and peak latencies. In transgenic mice, GFAP staining was more intense and extended than in control mice, and increased with increasing age; neurofilament staining showed swollen and partially degenerated axons in old transgenic mice. The IOP of young transgenic mice was similar to that of control mice and did not significantly change with increasing age.CONCLUSIONS. Transgenic mice expressing mutated human myocilin display progressive agerelated changes in RGC electrical responsiveness that are not associated with IOP elevation but are associated with marked astrogliosis and axonopathy. Our results support the view that MYOC expression in the optic nerve may impact structural, metabolic, or neurotrophic support to RGC axons, thereby influencing their susceptibility to glaucomatous damage independently of IOP.

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Voltage‐gated sodium channel‐dependent retroaxonal modulation of photoreceptor function during post‐natal development in mice

Smith

Côté

Tremblay

2021

Developmental Neurobiology

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During development, neural networks must adapt to appropriately encode environmental input. Synaptic modification by activity-induced long-term potentiation and long-term depression is a fundamental process of forming mature neural circuits (Feldman & Knudsen, 1998;Katz & Shatz, 1996;Zhang & Poo, 2001). Long-range spread of retrograde signals from postsynaptic neurons leading to changes in excitability of presynaptic cells has been demonstrated in both cultured cells (Ganguly et al., 2001;Li et al., 2004) and the developing retinotectal circuit (Du & Poo, 2004;Du et al., 2009). In-vivo, a long-range rapid retrograde feedback from the output synapses of the retinal ganglion cells (RGC) in the optic tectum has been documented to influence their input synapses from the bipolar

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Retrograde Signaling in the Optic Nerve Is Necessary for Electrical Responsiveness of Retinal Ganglion Cells

Cited by 45 publications

References 61 publications

Robust Mouse Pattern Electroretinograms Derived Simultaneously From Each Eye Using a Common Snout Electrode

Robust Mouse Pattern Electroretinograms Derived Simultaneously From Each Eye Using a Common Snout Electrode

Transgenic Mice Expressing Mutated Tyr437His Human Myocilin Develop Progressive Loss of Retinal Ganglion Cell Electrical Responsiveness and Axonopathy With Normal IOP

Voltage‐gated sodium channel‐dependent retroaxonal modulation of photoreceptor function during post‐natal development in mice

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