ATP can promote activation and deactivation of the rod cGMP‐phosphodiesterase

Kamps, K.M.P.; Hofmann, Klaus Peter

doi:10.1016/0014-5793(86)81025-0

Cited by 8 publications

(8 citation statements)

References 18 publications

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“…Retinas were incubated for 10 minutes in hypotonic buffer supplemented with 1 mM ATP [Bitensky et al, 1975;Kamps and Hofmann, 1986] and 5μM GTPγS [Wensel and Stryer, 1986]; then, for 2 extra minutes, they were either maintained in the dark or exposed to room light. Retinas were then homogenized, centrifuged for 10 minutes at 8,000 g and supernatants collected.…”

Section: Pde Activity Assaymentioning

confidence: 99%

Transgenic mice carrying theH258N mutation in the gene encoding the β-subunit of phosphodiesterase-6 (PDE6B) provide a model for human congenital stationary night blindness

Tsang

Woodruff

et al. 2007

Hum. Mutat.

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Mutations in the β-subunit of cGMP-phosphodiesterase (PDE6β) can lead to either progressive retinal disease, such as human retinitis pigmentosa (RP), or stationary disease, such as congenital stationary night blindness (CSNB). Individuals with CSNB in the Rambusch pedigree were found to carry the H258N allele of PDE6B (MIM# 180072); a similar mutation was not found in RP patients. This report describes an individual carrying the H258N allele, who presented with generalized retinal dysfunction affecting the rod system and a locus of dysfunction at the rod-bipolar interface. Also described are preclinical studies in which transgenic mice with the H258N allele were generated to study the pathophysiological mechanisms of CSNB. While Pde6b rd1 /Pde6b rd1 mice have severe photoreceptor degeneration, as in human RP, the H258N transgene rescued these cells. The cGMP-PDE6 activity of dark-adapted H258N mice showed an approximate three-fold increase in the rate of retinal cGMP hydrolysis: from 130.1 nmol × min −1 × nmol −1 rhodopsin in wild-type controls to 319.2 nmol × min −1 × nmol −1 rhodopsin in mutants, consistent with the hypothesis that inhibition of the PDE6β activity by the regulatory PDE6γ subunit is blocked by this mutation. In the albino (B6CBA × FVB) F2 hybrid background, electroretinograms (ERG) from H258N mice were similar to those obtained from affected Rambusch family members, as well as humans with the most common form of CSNB (X-linked), demonstrating a selective loss of the b-wave with relatively normal awaves. When the H258N allele was introduced into the DBA background, there was no evidence of selective reduction in b-wave amplitudes; rather a-and b-wave amplitudes were both reduced. Thus, factors other than the PDE6B mutation itself could contribute to the variance of an

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Section: Pde Activity Assaymentioning

confidence: 99%

Transgenic mice carrying theH258N mutation in the gene encoding the β-subunit of phosphodiesterase-6 (PDE6B) provide a model for human congenital stationary night blindness

Tsang

Woodruff

et al. 2007

Hum. Mutat.

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“…Among the several types of LS signal described previously is the amplified, transient ("AT") response recorded from permeabilized bovine ROS (8,9). The AT signal appears to monitor the activation of PDEi.e., G* + PDE-I G*'I + PDE*, where I is the inhibitory subunit of PDE (1,10).…”

mentioning

confidence: 99%

Photic modulation of a highly sensitive, near-infrared light-scattering signal recorded from intact retinal photoreceptors.

Pepperberg

Kahlert

Krause

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition to R*-transducin interactions, transducinphosphodiesterase (PDE) interactions were shown to generate a distinct scattering signal. This amplified, transient (AT) signal was demonstrated in suspensions of bovine rod OSs (62,63) and bovine retinal explants (64). Pepperberg et al showed that the scattering changes were present in low Na + solutions, even when the ERG response was completely extinguished (64), thereby ruling out the possibility that the former were due to the shifting Na + gradient underlying membrane hyperpolarization.…”

Section: Optical Signatures Of Signal Transduction In Neurons or Intrinsic Signalsmentioning

confidence: 98%

Toward a clinical optoretinogram: a review of noninvasive, optical tests of retinal neural function

Jonnal¹

2021

Ann Transl Med

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The past few years have witnessed rapid development of the optoretinogram-a noninvasive, optical measurement of neural function in the retina, and especially the photoreceptors (Ph). While its recent development has been rapid, it represents the culmination of hundreds of experiments spanning decades.Early work showed measurable and reproducible changes in the optical properties of retinal explants and suspensions of Ph, and uncovered some of the biophysical and biochemical mechanisms underlying them.That work thus provided critical motivation for more recent work based on clinical imaging platforms, whose eventual goal is the improvement of ophthalmic care and streamlining the discovery of novel therapeutics.The first part of this review consists of a selective summary of the early work, and identifies four kinds of stimulus-evoked optical signals that have emerged from it: changes in light scattered from the membranous discs of the Ph's outer segment (OS), changes in light scattered by the front and back boundaries of the OS, rearrangement of scattering material in and near the OS, and changes in the OS length. In the past decade, all four of these signals have continued to be investigated using imaging systems already used in the clinic or intended for clinical and translational use. The second part of this review discusses these imaging modalities, their potential to detect and quantify the signals of interest, and other factors influencing their translational promise. Particular attention is paid to phase-sensitive optical coherence tomography (OCT) with adaptive optics (AO), a method in which both the amplitude and the phase of light reflected from individual Ph is monitored as visible stimuli are delivered to them. The record of the light's phase is decoded to reveal a reproducible pattern of deformation in the OS, while the amplitude reveals changes in scattering and structural rearrangements. The method has been demonstrated in a few labs and has been used to measure responses from both rods and cones. With the ability to detect responses to stimuli isomerizing less than 0.01% of photopigment, this technique may prove to be a quick, noninvasive, and objective way to measure subtle disease-related dysfunction at the cellular level, and thus to provide an entirely new and complementary biomarker for retinal disease and recovery.

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ATP can promote activation and deactivation of the rod cGMP‐phosphodiesterase

Cited by 8 publications

References 18 publications

Transgenic mice carrying theH258N mutation in the gene encoding the β-subunit of phosphodiesterase-6 (PDE6B) provide a model for human congenital stationary night blindness

Transgenic mice carrying theH258N mutation in the gene encoding the β-subunit of phosphodiesterase-6 (PDE6B) provide a model for human congenital stationary night blindness

Photic modulation of a highly sensitive, near-infrared light-scattering signal recorded from intact retinal photoreceptors.

Toward a clinical optoretinogram: a review of noninvasive, optical tests of retinal neural function

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