Adaptive potentiation in rod photoreceptors after light exposure

McKeown, Alex; Kraft, Timothy W.

doi:10.1085/jgp.201411163

Cited by 12 publications

(31 citation statements)

References 36 publications

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“…In both mouse and primate rods, regeneration of bleached rhodopsin with 25 μ m 11‐ cis retinal decreases the magnitude of AP compared to that of the dark‐adapted mouse: mean ± SD AP of 33 ± 3% (regenerated mouse AP: 19 ± 3%, n = 4 cells, P < 0.05; regenerated primate AP: 17 ± 1%, n = 4 cells, P < 0.01; example cells are shown in Fig. ) (McKeown & Kraft, ). When the same amount of 11‐ cis retinal was applied to dark‐adapted mouse rods, the magnitude of AP was decreased by an amount similar to that in the light‐adapted cells (20 ± 6%, n = 4 cells, P < 0.05).…”

Section: Resultsmentioning

confidence: 98%

“…In general, photoreceptor sensitivity decreases as photon absorption rates increase. Recently, a new form of adaptation was identified where rods exhibit a light‐dependent hypersensitivity following periods of saturating illumination (McKeown & Kraft, ; McKeown et al . ).…”

Section: Introductionmentioning

confidence: 99%

“…The signalling of AP appears to be a result of the activity of the insulin‐like growth factor‐1 receptor (IGF‐1R) acting to dephosphorylate the cyclic nucleotide (CNG) channels, thereby increasing their sensitivity for their ligand cGMP (Savchenko et al . ; McKeown & Kraft, ). The results reported in the present study link AP directly with photon capture and changes in CNG sensitivity, and we introduce an extracellular signalling pathway that involves the release of retinal chromophore.…”

Section: Introductionmentioning

confidence: 99%

“…). The IGF‐1 receptor also appears to be activated by light because IGF‐1R inhibition eliminated the AP form of light adaptation in mouse rods (McKeown & Kraft, ). The work reported in the present study investigates the mechanism of light‐dependent IGF‐1 activation.…”

Section: Introductionmentioning

confidence: 99%

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Signalling beyond photon absorption: extracellular retinoids and growth factors modulate rod photoreceptor sensitivity

McKeown¹,

Pitale²,

Kraft

2016

The Journal of Physiology

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Key pointsr We propose that the end product of chromophore bleaching in rod photoreceptors, all-trans retinol, is part of a feedback loop that increases the sensitivity of the phototransduction cascade in rods.r A previously described light-induced hypersensitivity in rods, termed adaptive potentiation, is reduced by exogenously applied all-trans retinol but not all-trans retinal.r This potentiation is produced by insulin-like growth factor-1, whose binding proteins are located in the extracellular matrix, even in our isolated retina preparation after removal of the retinal pigmented epithelium.r Simple modelling suggests that the light stimuli used in the present study will produce sufficient all-trans retinol within the interphotoreceptor matrix to explain the potentiation effect.Abstract Photoreceptors translate the absorption of photons into electrical signals for propagation through the visual system. Mammalian photoreceptor signalling has largely been studied in isolated cells, and such studies have necessarily avoided the complex environment of supportive proteins that surround the photoreceptors. The interphotoreceptor matrix (IPM) contains an array of proteins that aid in both structural maintenance and cellular homeostasis, including chromophore turnover. In signalling photon absorption, the chromophore 11-cis retinal is first isomerized to all-trans retinal, followed by conversion to all-trans retinol (ROL) for removal from the photoreceptor. Interphotoreceptor retinoid-binding protein (IRBP) is the most abundant protein in the IPM, and it promotes the removal of bleached chromophores and recycling in the nearby retinal pigment epithelium. By studying the light responses of isolated mouse retinas, we demonstrate that ROL can act as a feedback signal onto photoreceptors that influences the sensitivity of phototransduction. In addition to IRBP, the IPM also contains insulinlike growth factor-1 (IGF-1) and its associated binding proteins, although their functions have not yet been described. We demonstrate that extracellular application of physiological concentrations of IGF-1 can increase rod photoreceptor sensitivity in mammalian retinas. We also determine that chromophores and growth factors can limit the range of a newly described form of photoreceptor light adaptation. Finally, fluorescent antibodies demonstrate the presence of IRBP and IGFBP-3 in isolated retinas. A simple model of the formation and release of ROL into the extracellular space quantitatively describes this novel feedback loop.

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Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Signalling beyond photon absorption: extracellular retinoids and growth factors modulate rod photoreceptor sensitivity

McKeown¹,

Pitale²,

Kraft

2016

The Journal of Physiology

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“…To confirm the observed increase in gain we analyzed isolated retinas that were pharmacologically manipulated to eliminate inner retina responses, allowing analysis of the photoreceptor fast PIII response (Figure 5A-B; Table 1) [29,30]. Figure 5C shows a comparison of gain estimates to the rising phase of the a-wave in WT and tg isolated retinas using Equation 2 (see Methods).…”

Section: Rods Overexpressing Garp2 Exhibit Increased Phototransductiomentioning

confidence: 99%

Overexpression of rod photoreceptor glutamic acid rich protein 2 (GARP2) increases gain and slows recovery in mouse retina

Sarfare

McKeown

Messinger

et al. 2014

Cell Communication and Signaling

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Background: The rod photoreceptor cGMP-gated cation channel, consisting of three α-and one β subunit, controls ion flow into the rod outer segment (ROS). In addition to the β-subunit, the Cngb1 locus encodes an abundant soluble protein, GARP2 that binds stoichiometrically to rod photoreceptor cGMP phosphodiesterase type 6 (PDE6). To examine the in vivo functional role of GARP2 we generated opsin promoter-driven transgenic mice overexpressing GARP2 three-fold specifically in rod photoreceptors. Results: In the GARP2 overexpressing transgenic mice (tg), the endogenous channel β-subunit, cGMP phosphodiesterase α-subunit, peripherin2/RDS and guanylate cyclase I were present at WT levels and were properly localized within the ROS. While localized properly within ROS, two proteins cGMP phosphodiesterase α-subunit (1.4-fold) and cGMP-gated cation channel α-subunit (1.2-fold) were moderately, but significantly elevated. Normal stratification of all retinal layers was observed, and ROS were stable in numbers but were 19% shorter than WT. Analysis of the photoresponse using electroretinography (ERG) showed that tg mice exhibit no change in sensitivity indicating overall normal rod function, however two parameters of the photoresponse significantly differed from WT responses. Fitting of the rising phase of the ERG a-wave to an accepted model of phototransduction showed a two-fold increase in phototransduction gain in the tg mice. The increase in gain was confirmed in isolated retinal tissue and by suction electrode recordings of individual rod photoreceptor cells. A measure of response recovery, the dominant time constant (τ D ) was elevated 69% in isolated retina compared to WT, indicating slower shutoff of the photoresponse.

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Light-gated amorphous carbon memristors with indium-free transparent electrodes

Murdoch

Raeber

Zhao

et al. 2019

Carbon

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Adaptive potentiation in rod photoreceptors after light exposure

Abstract: After illumination, rod photoreceptors show a paradoxical increase in sensitivity to light.

Cited by 12 publications

References 36 publications

Signalling beyond photon absorption: extracellular retinoids and growth factors modulate rod photoreceptor sensitivity

Signalling beyond photon absorption: extracellular retinoids and growth factors modulate rod photoreceptor sensitivity

Overexpression of rod photoreceptor glutamic acid rich protein 2 (GARP2) increases gain and slows recovery in mouse retina

Light-gated amorphous carbon memristors with indium-free transparent electrodes

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