Two neuronal retinal components of the electroretinogram c-wave

Hanitzsch, Renate; Lichtenberger, T.

doi:10.1007/bf02582985

Cited by 12 publications

(5 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Electroretinogram (ERG) assesses the electrical activity of the retina in response to a light stimulus. ERG c-waves measure the variation in the standing potential across Bruch’s membrane and is associated with the health of RPE cells [ 32 ]. ERG c-wave measurements displayed the highest activity in young adult mice, which significantly decreased in the extremely old mice (34-months-old) on the control diet, moreover, the c-waves of old mice without microglia were reduced even more (Fig.…”

Section: Resultsmentioning

confidence: 99%

Microglia preserve visual function in the aging retina by supporting retinal pigment epithelial health

Karg,

Moorefield,

Hoffmann

et al. 2023

Immun Ageing

View full text Add to dashboard Cite

Background Increased age is a risk factor for the development and progression of retinal diseases including age-related macular degeneration (AMD). Understanding the changes that occur in the eye due to aging is important in enhancing our understanding of AMD pathogenesis and the development of novel AMD therapies. Microglia, the resident brain and retinal immune cells are associated with both maintaining homeostasis and protection of neurons and loss of microglia homeostasis could be a significant player in age related neurodegeneration. One important characteristic of retinal aging is the migration of microglia from the inner to outer retina where they reside in the subretinal space (SRS) in contact with the retinal pigment epithelial (RPE) cells. The role of aged subretinal microglia is unknown. Here, we depleted microglia in aged C57/BL6 mice fed for 6 weeks with a chow containing PLX5622, a small molecule inhibitor of colony-stimulating factor-1 receptor (Csf1r) required for microglial survival. Results The subretinal P2RY12 + microglia in aged mice displayed a highly amoeboid and activated morphology and were filled with autofluorescence droplets reminiscent of lipofuscin. TEM indicates that subretinal microglia actively phagocytize shed photoreceptor outer segments, one of the main functions of retinal pigmented epithelial cells. PLX5622 treatment depleted up to 90% of the retinal microglia and was associated with significant loss in visual function. Mice on the microglia depletion diet showed reduced contrast sensitivity and significantly lower electroretinogram for the c-wave, a measurement of RPE functionality, compared to age-matched controls. The loss of c-wave coincided with a loss of RPE cells and increased RPE swelling in the absence of microglia. Conclusions We conclude that microglia preserve visual function in aged mice and support RPE cell function, by phagocytosing shed photoreceptor outer segments and lipids, therefore compensating for the known age-related decline of RPE phagocytosis.

show abstract

Section: Resultsmentioning

confidence: 99%

Microglia preserve visual function in the aging retina by supporting retinal pigment epithelial health

Karg,

Moorefield,

Hoffmann

et al. 2023

Immun Ageing

View full text Add to dashboard Cite

show abstract

“…The negative-going a-wave and the positive-going b-wave originate from photoreceptors and rod bipolar cells, respectively (21)(22)(23)(24)(25), whereas the sources of the positive-going c-wave are the RPE and retinal glial cells (26). In our study, in Aβ(1-42)-injected mice, there was a statistically significant decrease in the a-, b-and c-wave amplitude compared to the control group (Fig.…”

Section: Discussionmentioning

confidence: 47%

“…Rod bipolar cells are the source of the b-wave in the dark-adapted retina (23)(24)(25). RPE cells are the source of the positive-going c-wave (26). Representative waveforms of the maximal ERG scotopic response evoked by a single flash at 1.125 cd * s/m 2 are illustrated in Fig.…”

Section: Aβ Peptide Leads To Impairment Of Visual Function In Animalsmentioning

confidence: 99%

Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration

Liu

Cao

Yang

et al. 2014

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. Drusen are considered a hallmark characteristic of age-related macular degeneration (AMD). In our previous study, we found that amyloid-β (Aβ) peptide, a component of drusen, induced the cells of the retinal pigment epithelium (RPE; RPE cells) to enter senescence; however, its effects in vivo remain unknown. Thus, the present study was carried out to explore the in vivo effects of Aβ peptide on RPE cell senescence and senescence-associated inflammation in C57BL/6 mice. C57BL/6 mice received a subretinal injection of Aβ(1-42) peptide; on day 7 post-injection, the mice were anesthetized and subjected to whole-body perfusion with 4% paraformaldehyde (PFA) in PBS and the whole eyes were then enucleated. Retinal function was assessed by electroretinography (ERG), and the morphological characteristics of the retina were examined by light and electron microscopy. Fundus autofluorescence (FAF) was examined by confocal scanning laser ophthalmoscopy (cSLO). The expression of p16INK4a , a marker of cellular senescence, was examined by immunofluorescence staining and western blot analysis. The RPE-choroid was analyzed for cytokine expression by RT-PCR. In Aβ(1-42)-injected mice, scotopic ERG responses declined. Degenerative alterations, including the disruption of the inner segment (IS)/outer segment (OS) junction and extensive vacuolation and thickness of Bruch's membrane (BrM) were observed under a a light microscope. The accumulation of vacuoles and the loss of basal infoldings in the RPE were identified using an electron microscope. FAF and p16INK4a expression increased in Aβ(1-42)-injected mice. In addition, Aβ(1-42) upregulated interleukin (IL)-6 and IL-8 gene expression in the RPE-choroid. In conclusion, our results confirm the effects of Aβ(1-42) peptide on RPE senescence in vivo. The Aβ-injected mice developed AMD-like ocular pathology. It is thus suggested that RPE cell senescence is a potential mechanistic link between inflammation and retinal degeneration.

show abstract

“…The second main component of the ERG is the b-wave, which is a positive deflection associated with the activity of depolarising bipolar cells (BC) [ 4 , 13 , 23 , 24 , 25 ]. In addition to the neuroretinal a- and b-wave responses, glial and retinal pigment epithelial cell activity is also registered in the ERG signal as the c-wave, which is a slow positive-deflection signal following the b-wave [ 26 , 27 , 28 ]. Since the retinal explants used in the present study consist only of a thin layer of retinal pigment epithelial cells without attachment to the choroid, the c-wave response will not be further considered in this article.…”

Section: Introductionmentioning

confidence: 99%

Using Micro-Electrode-Array Recordings and Retinal Disease Models to Elucidate Visual Functions: Simultaneous Recording of Local Electroretinograms and Ganglion Cell Action Potentials Reveals the Origin of Retinal Oscillatory Potentials

et al. 2023

View full text Add to dashboard Cite

Background: The electroretinogram (ERG) is an essential diagnostic tool for visual function, both in clinical and research settings. Here, we establish an advanced in vitro approach to assess cell-type-specific ERG signal components. Methods: Retinal explant cultures, maintained under entirely controlled conditions, were derived from wild-type mice and rd10 rod- and cpfl1 cone-degeneration mouse models. Local micro-ERG (µERG) and simultaneous ganglion cell (GC) recordings were obtained from the retinal explants using multi-electrode arrays. Band-pass filtering was employed to distinguish photoreceptor, bipolar cell, amacrine cell (AC), and GC responses. Results: Scotopic and photopic stimulation discriminated between rod and cone responses in wild-type and mutant retina. The 25 kHz sampling rate allowed the visualization of oscillatory potentials (OPs) in extraordinary detail, revealing temporal correlations between OPs and GC responses. Pharmacological isolation of different retinal circuits found that OPs are generated by inner retinal AC electrical synapses. Importantly, this AC activity helped synchronise GC activity. Conclusion: Our µERG protocol simultaneously records the light-dependent activities of the first-, second-, and third-order neurons within the native neuronal circuitry, providing unprecedented insights into retinal physiology and pathophysiology. This method now also enables complete in vitro retinal function testing of therapeutic interventions, providing critical guidance for later in vivo investigations.

show abstract

Two neuronal retinal components of the electroretinogram c-wave

Cited by 12 publications

References 18 publications

Microglia preserve visual function in the aging retina by supporting retinal pigment epithelial health

Microglia preserve visual function in the aging retina by supporting retinal pigment epithelial health

Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration

Using Micro-Electrode-Array Recordings and Retinal Disease Models to Elucidate Visual Functions: Simultaneous Recording of Local Electroretinograms and Ganglion Cell Action Potentials Reveals the Origin of Retinal Oscillatory Potentials

Contact Info

Product

Resources

About