Characterization of connexin36 gap junctions in the human outer retina

Kántor, Orsolya; Benkő, Zsigmond; Énzsöly, Anna; Chiu, David; Naumann, Angela; Nitschke, Roland; Szabó, Arnold; Pálfi, Emese; Orbán, József; Nyitrai, Miklós; Németh, János; Szél, Ágoston; Lukáts, Ákos; Völgyi, Béla

doi:10.1007/s00429-015-1082-z

Cited by 22 publications

(29 citation statements)

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“…Despite the similarity, subtle differences in the ON sublayer preference of Cx36 plaques and the presence of subpedicle Cx36 aggregations in the OPL was observed. The wealth of subpedicle Cx36 aggregates in the human OPL has been reported previously (Kántor et al, 2016a) and shown that these structures are GJ sites formed by bipolar cell dendrite terminal endings. GJs in subpedicle aggregates connect bipolar cell dendrites that are postsynaptic to the same cone pedicle, thus likely serve a function necessary for photopic visual signaling.…”

Section: Discussionmentioning

confidence: 66%

“…Whereas the human and guinea pig retinas displayed robust Cx36 labels in the outer retina, the rabbit and the squirrel monkey retinas exhibited only sporadic and faint Cx36 puncta. Cx36 plaques in the human and guinea pig retinas were found throughout the OPL and many of them formed strip-like conglomerates that resembled subpedicle Cx36 aggregates found in some species (Feigenspan et al, 2004; O’Brien et al, 2012; Kántor et al, 2016a). Cx36 plaques scattered throughout the inner retina of all four group 2 species, however, their distributions showed some differences as well.…”

Section: Resultsmentioning

confidence: 90%

“…Similar to the dog, the cat and the ferret retinas displayed only few solitary Cx36 plaques in the OPL, the mouse and rat retinas showed somewhat more, whereas the human retina (similar to the guinea pig retina) exhibited many Cx36 plaques. The observed Cx36 plaques in the OPL might be expressed by two neuron populations in mammals; cone photoreceptors that form GJs with each other and/or with rods (Schneeweis and Schnapf, 1995; Deans et al, 2002; Kántor et al, 2016a) and cone bipolar cells that maintain subpedicular bipolar-to-bipolar junctions (Feigenspan et al, 2004; Bolte et al, 2016; Kántor et al, 2016a). The above observed difference in Cx36 expression in the OPL reflects the prevalence of either of the two junction systems in the examined mammalian species.…”

Section: Discussionmentioning

confidence: 99%

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Connexin36 Expression in the Mammalian Retina: A Multiple-Species Comparison

Kovács-Öller

Debertin

Balogh

et al. 2017

Front. Cell. Neurosci.

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Much knowledge about interconnection of human retinal neurons is inferred from results on animal models. Likewise, there is a lack of information on human retinal electrical synapses/gap junctions (GJ). Connexin36 (Cx36) forms GJs in both the inner and outer plexiform layers (IPL and OPL) in most species including humans. However, a comparison of Cx36 GJ distribution in retinas of humans and popular animal models has not been presented. To this end a multiple-species comparison was performed in retinas of 12 mammals including humans to survey the Cx36 distribution. Areas of retinal specializations were avoided (e.g., fovea, visual streak, area centralis), thus observed Cx36 distribution differences were not attributed to these species-specific architecture of central retinal areas. Cx36 was expressed in both synaptic layers in all examined retinas. Cx36 plaques displayed an inhomogenous IPL distribution favoring the ON sublamina, however, this feature was more pronounced in the human, swine and guinea pig while it was less obvious in the rabbit, squirrel monkey, and ferret retinas. In contrast to the relative conservative Cx36 distribution in the IPL, the labels in the OPL varied considerably among mammals. In general, OPL plaques were rare and rather small in rod dominant carnivores and rodents, whereas the human and the cone rich guinea pig retinas displayed robust Cx36 labels. This survey presented that the human retina displayed two characteristic features, a pronounced ON dominance of Cx36 plaques in the IPL and prevalent Cx36 plaque conglomerates in the OPL. While many species showed either of these features, only the guinea pig retina shared both. The observed similarities and subtle differences in Cx36 plaque distribution across mammals do not correspond to evolutionary distances but may reflect accomodation to lifestyles of examined species.

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Section: Discussionmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Connexin36 Expression in the Mammalian Retina: A Multiple-Species Comparison

Kovács-Öller

Debertin

Balogh

et al. 2017

Front. Cell. Neurosci.

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“…; Kántor et al. ; Asteriti et al. ), and as elements of electrical synapses, connexins are involved in signal conduction and neuronal excitation control (Maxeiner ).…”

Section: Discussionmentioning

confidence: 99%

Electrical synapses interconnecting axons revealed in the optic nerve head – a novel model of gap junctions’ involvement in optic nerve function

Smędowski

Akhtar

Liu

et al. 2019

Acta Ophthalmologica

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Purpose: To characterize newly discovered electrical synapses, formed by connexin (Cx) 36 and 45, between neighbouring axons within the optic nerve head. Methods: Twenty-five Wistar rats were killed by CO 2 inhalation. Proximal and distal optic nerve (ON) stumps were collected and processed for immunostainings, electron microscopy (EM) with immunogold labelling, PCR and Western blots (WB). Additional 15 animals were deeply anaesthetized, and flash visual evoked potentials (fVEP) after retrobulbar injection of saline (negative control) or 100 lM meclofenamic acid solution (gap junctions' blocker) were recorded. Human paraffin cross-sections of eyeballs for immunostainings were obtained from the Human Eye Biobank for Research. Results: Immunostainings of both rat and human ON revealed the presence of Cx45 and 36 colocalizing with b3-tubulin, but not with glial fibrillary acidic protein (GFAP). In WB, Cx36 content in optic nerve was approximately halved when compared with retina (0.58 AE 0.005 in proximal stump and 0.44 AE 0.02 in distal stump), Cx45 showed higher levels (0.68 AE 0.01 in proximal stump and 0.9 AE 0.07 in distal stump). In immunogold-EM of optic nerve sections, we found electric synapses (formed mostly by Cx45) directly coupling neighbouring axons. In fVEP, blocking of gap junctions with meclofenamic acid resulted in significant prolongation of the latency of P1 wave up to 160% after 30 min (p < 0.001). Conclusions: Optic nerve (ON) axons are equipped with electrical synapses composed of neuronal connexins, especially Cx45, creating direct morphological and functional connections between each other. This finding could have substantial implications for understanding of the pathogenesis of various optic neuropathies and identifies a new potential target for a therapeutic approach.Additional Supporting Information may be found in the online version of this article: Fig. S1. The method of VEP electrodes placement.

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“…For OFF-cone bipolar cells, there are a number of studies in a variety of species that strongly suggest the presence of gap junctions, both between the dendrites (Mills 1999;Feigenspan et al 2004;O'Brien et al 2012;Kántor et al 2016) and the axon terminals (Kolb 1979;Jacoby and Marshak 2000;Omi 2015, 2017;Kántor et al 2017) of these cells. In addition, there is evidence that the gap junctions at the dendrites of OFFcone bipolar cells contain Cx36 (Feigenspan et al 2004;O'Brien et al 2012;Kántor et al 2016). Heterologous gap junctions between adjacent ON-cone bipolars have also been reported (Cohen and Sterling 1990;Tsukamoto and Omi 2017).…”

Section: Evidence For Gap Junctions Involving Cone Bipolar Cellsmentioning

confidence: 99%

Differential Contribution of Gap Junctions to the Membrane Properties of ON- and OFF-Bipolar Cells of the Rat Retina

2020

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Gap junctions are ubiquitous within the retina, but in general, it remains to be determined whether gap junction coupling between specific cell types is sufficiently strong to mediate functionally relevant coupling via electrical synapses. From ultrastructural, tracer coupling and immunolabeling studies, there is clear evidence for gap junctions between cone bipolar cells, but it is not known if these gap junctions function as electrical synapses. Here, using whole-cell voltage-clamp recording in rat (male and female) retinal slices, we investigated whether the gap junctions of bipolar cells make a measurable contribution to the membrane properties of these cells. We measured the input resistance (R N) of bipolar cells before and after applying meclofenamic acid (MFA) to block gap junctions. In the presence of MFA, R N of ON-cone bipolar cells displayed a clear increase, paralleled by block of the electrical coupling between these cells and AII amacrine cells in recordings of coupled cell pairs. For OFF-cone and rod bipolar cells, R N did not increase in the presence of MFA. The results for rod bipolar cells are consistent with the lack of gap junctions in these cells. However, for OFF-cone bipolar cells, our results suggest that the morphologically identified gap junctions between these cells do not support a junctional conductance that is sufficient to mediate effective electrical coupling. Instead, these junctions might play a role in chemical and/or metabolic coupling between subcellular compartments.

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Characterization of connexin36 gap junctions in the human outer retina

Cited by 22 publications

References 64 publications

Connexin36 Expression in the Mammalian Retina: A Multiple-Species Comparison

Connexin36 Expression in the Mammalian Retina: A Multiple-Species Comparison

Electrical synapses interconnecting axons revealed in the optic nerve head – a novel model of gap junctions’ involvement in optic nerve function

Differential Contribution of Gap Junctions to the Membrane Properties of ON- and OFF-Bipolar Cells of the Rat Retina

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