Where vision begins

Dell’Orco, Daniele; Koch, Karl‐Wilhelm; Rispoli, Giorgio

doi:10.1007/s00424-021-02605-3

Cited by 6 publications

(4 citation statements)

References 23 publications

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“…Loss of intracellular ATP will impair the function of plasma membrane Ca 2+ ATPase (PMCA), an active transporter that is crucial for keeping intracellular Ca 2+ levels low [ 65 ]. Remarkably, HDAC inhibition has been found to increase PMCA activity [ 66 , 67 ], which thus could enhance intracellular Ca 2+ clearance and reduce calpain activity.…”

Section: Discussionmentioning

confidence: 99%

Inherited Retinal Degeneration: Towards the Development of a Combination Therapy Targeting Histone Deacetylase, Poly (ADP-Ribose) Polymerase, and Calpain

et al. 2023

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Inherited retinal degeneration (IRD) represents a diverse group of gene mutation-induced blinding diseases. In IRD, the loss of photoreceptors is often connected to excessive activation of histone-deacetylase (HDAC), poly-ADP-ribose-polymerase (PARP), and calpain-type proteases (calpain). Moreover, the inhibition of either HDACs, PARPs, or calpains has previously shown promise in preventing photoreceptor cell death, although the relationship between these enzyme groups remains unclear. To explore this further, organotypic retinal explant cultures derived from wild-type mice and rd1 mice as a model for IRD were treated with different combinations of inhibitors specific for HDAC, PARP, and calpain. The outcomes were assessed using in situ activity assays for HDAC, PARP, and calpain, immunostaining for activated calpain-2, and the TUNEL assay for cell death detection. We confirmed that inhibition of either HDAC, PARP, or calpain reduced rd1 mouse photoreceptor degeneration, with the HDAC inhibitor Vorinostat (SAHA) being most effective. Calpain activity was reduced by inhibition of both HDAC and PARP whereas PARP activity was only reduced by HDAC inhibition. Unexpectedly, combined treatment with either PARP and calpain inhibitors or HDAC and calpain inhibitors did not produce synergistic rescue of photoreceptors. Together, these results indicate that in rd1 photoreceptors, HDAC, PARP, and calpain are part of the same degenerative pathway and are activated in a sequence that begins with HDAC and ends with calpain.

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Section: Discussionmentioning

confidence: 99%

Inherited Retinal Degeneration: Towards the Development of a Combination Therapy Targeting Histone Deacetylase, Poly (ADP-Ribose) Polymerase, and Calpain

et al. 2023

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“…A simple photoisomerization reaction (from the 11-cis retinal to the all-trans retinal) initiates a cascade of events in which ion channels close, cells hyperpolarize and ultimately neurotransmitters release towards the optical nerve halts, therefore stopping inhibitory effect on retinal ganglion cell stimulation and visual perception (Fig. 6a) [79]. Degenerative pathologies of the retina may cause blindness due to an irreversible damage or loss of the retinal photoreceptors, i.e.…”

Section: Azobenzene In Vision Restoration and Investigation Of Neuron...mentioning

confidence: 99%

New tricks and emerging applications from contemporary azobenzene research

Fedele

Ruoko

Kuntze

et al. 2022

Photochem Photobiol Sci

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Azobenzenes have many faces. They are well-known as dyes, but most of all, azobenzenes are versatile photoswitchable molecules with powerful photochemical properties. Azobenzene photochemistry has been extensively studied for decades, but only relatively recently research has taken a steer towards applications, ranging from photonics and robotics to photobiology. In this perspective, after an overview of the recent trends in the molecular design of azobenzenes, we highlight three research areas where the azobenzene photoswitches may bring about promising technological innovations: chemical sensing, organic transistors, and cell signaling. Ingenious molecular designs have enabled versatile control of azobenzene photochemical properties, which has in turn facilitated the development of chemical sensors and photoswitchable organic transistors. Finally, the power of azobenzenes in biology is exemplified by vision restoration and photactivation of neural signaling. Although the selected examples reveal only some of the faces of azobenzenes, we expect the fields presented to develop rapidly in the near future, and that azobenzenes will play a central role in this development.

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“…Two major cyclic nucleotide monophosphates, cGMP and cAMP, have distinct roles in the vertebrate phototransduction cascade. cGMP regulates the permeability of plasma membrane channels in photoreceptors and its role has been extensively studied (for review see [1,2]). After absorbing a quantum of light, a molecule of the visual pigment rhodopsin becomes active and activates several hundred molecules of the G-protein transducin.…”

Section: Introductionmentioning

confidence: 99%

Near-Saturating Light Induces a Rapid Increase in cAMP and Activates PKA in Rod Outer Segments of the Frog Retina

Chernyshkova,

Erofeeva,

Meshalkina

et al. 2023

Preprint

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The phototransduction cascade allows the photoreceptor to avoid saturation and retain the ability to detect light over a very wide range of intensities. The main second messenger of the cascade is cGMP and the main regulatory mechanism is calcium feedback, however some experimental data suggest that cAMP may also be involved in the regulation of the phototransduction cascade. For this to be the case, cAMP would have to change on a time scale of seconds. Currently, there are no data on the dynamics of changes in intracellular cAMP levels on this time scale, largely due to the specificity of the sensory modality of photoreceptors, where it is practically impossible to use conventional experimental approaches based on fluorescence methods. In the present work, we used the method of rapid cryofixation of retinal samples after light stimulation and subsequent isolation of outer segment preparations. Levels of cAMP were measured using highly sensitive metabolomics approaches. PKA activity was also measured in these samples by Western blot. We show that when illuminated with near-saturating but still moderate light, cAMP levels rise transiently within approximately the first second and then return to pre-stimulus levels. The increase in cAMP activates PKA, leading to phosphorylation of PKA-specific substrates in frog retinal outer segments.

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Where vision begins

Cited by 6 publications

References 23 publications

Inherited Retinal Degeneration: Towards the Development of a Combination Therapy Targeting Histone Deacetylase, Poly (ADP-Ribose) Polymerase, and Calpain

Inherited Retinal Degeneration: Towards the Development of a Combination Therapy Targeting Histone Deacetylase, Poly (ADP-Ribose) Polymerase, and Calpain

New tricks and emerging applications from contemporary azobenzene research

Near-Saturating Light Induces a Rapid Increase in cAMP and Activates PKA in Rod Outer Segments of the Frog Retina

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