TRPV4 Does Not Regulate the Distal Retinal Light Response

Yarishkin, Oleg; Phuong, Tam T. T.; Lakk, Mónika; Križaj, David

doi:10.1007/978-3-319-75402-4_67

Cited by 12 publications

(5 citation statements)

References 28 publications

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“…In contrast to the canonical TRPC1 isoform which is expressed in most retinal cells ( Molnar et al, 2012 , 2016 ), the most extensively studied isoform – TRPV1 – was localized to photoreceptors and subsets of RGCs, bipolar, and amacrine cells ( Yazulla, 2008 ; Middleton and Protti, 2011 ; Ryskamp et al, 2014a ; Jo et al, 2017 ). Its cognate, TRPV4, has been detected in RGCs, Müller glia, and endothelial cells ( Ryskamp et al, 2011 , 2014b ; Jo et al, 2015 ; Phuong et al, 2017 ; Taylor et al, 2017 ) but, unlike TRPV1, appears to be absent from amacrine, bipolar, and photoreceptor cells ( Yarishkin et al, 2018 ). The relative expression of vanilloid isoforms across RGCs is unknown, nor is it clear whether TRPV1 and TRPV4 colocalize and/or can interact.…”

Section: Introductionmentioning

confidence: 99%

Polymodal TRPV1 and TRPV4 Sensors Colocalize but Do Not Functionally Interact in a Subpopulation of Mouse Retinal Ganglion Cells

Lakk

Young

Baumann

et al. 2018

Front. Cell. Neurosci.

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Retinal ganglion cells (RGCs) are projection neurons that transmit the visual signal from the retina to the brain. Their excitability and survival can be strongly influenced by mechanical stressors, temperature, lipid metabolites, and inflammatory mediators but the transduction mechanisms for these non-synaptic sensory inputs are not well characterized. Here, we investigate the distribution, functional expression, and localization of two polymodal transducers of mechanical, lipid, and inflammatory signals, TRPV1 and TRPV4 cation channels, in mouse RGCs. The most abundant vanilloid mRNA species was Trpv4, followed by Trpv2 and residual expression of Trpv3 and Trpv1. Immunohistochemical and functional analyses showed that TRPV1 and TRPV4 channels are expressed as separate molecular entities, with TRPV1-only (∼10%), TRPV4-only (∼40%), and TRPV1 + TRPV4 (∼10%) expressing RGC subpopulations. The TRPV1 + TRPV4 cohort included SMI-32-immunopositive alpha RGCs, suggesting potential roles for polymodal signal transduction in modulation of fast visual signaling. Arguing against obligatory heteromerization, optical imaging showed that activation and desensitization of TRPV1 and TRPV4 responses evoked by capsaicin and GSK1016790A are independent of each other. Overall, these data predict that RGC subpopulations will be differentially sensitive to mechanical and inflammatory stressors.

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Section: Introductionmentioning

confidence: 99%

Polymodal TRPV1 and TRPV4 Sensors Colocalize but Do Not Functionally Interact in a Subpopulation of Mouse Retinal Ganglion Cells

Lakk

Young

Baumann

et al. 2018

Front. Cell. Neurosci.

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“…In a strain of TRPV4 transgenic mice, a previous study ( Yarishkin et al, 2018 ) did not report changes in ERG a- and b-wave evoked by full-field lights of 0.00025–79 cd.s/m 2 , presumably white light in the range of 0.03 to 9,559 Rh*rod −1 s −1 or 17.6 to 5.5 × 10 6 Rh*rod −1 s −1 , and it was uncertain whether the spectrum and intensity of the light stimuli and adaption conditions contributed to the negative results. Rods and RBCs are highly light-sensitive, and light stimuli and background illumination may differentially depolarize cones and rods to variably regulate the driving force of I C-IN-TRPV4 in rods and cones.…”

Section: Discussionmentioning

confidence: 99%

TRPV4 affects visual signals in photoreceptors and rod bipolar cells

Long,

Kozhemyakin,

et al. 2024

Front. Cell. Neurosci.

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IntroductionMechanical sensitive channels expressed in mammalian retinas are effectors of elevated pressure stresses, but it is unclear how their activation affects visual function in pressure-related retinal disorders.MethodsThis study investigated the role of the transient potential channel vanilloid TRPV4 in photoreceptors and rod bipolar cells (RBCs) with immunohistochemistry, confocal microscopy, electroretinography (ERG), and patch-clamp techniques.ResultsTRPV4 immunoreactivity (IR) was found in the outer segments of photoreceptors, dendrites and somas of PKCα-positive RBCs and other BCs, plexiform layers, and retinal ganglion cells (RGCs) in wild-type mice. TRPV4-IR was largely diminished in the retinas of homozygous TRPV4 transgenic mice. Genetically suppressing TRPV4 expression moderately but significantly enhanced the amplitude of ERG a- and b-waves evoked by scotopic and mesopic lights (0.55 to 200 Rh*rod−1 s−1) and photopic lights (105–106 Rh*rod−1 s−1) compared to wild-type mice in fully dark-adapted conditions. The implicit time evoked by dim lights (0.55 to 200 Rh*rod−1 s−1) was significantly decreased for b-waves and elongated for a-waves in the transgenic mice. ERG b-wave evoked by dim lights is primarily mediated by RBCs, and under voltage-clamp conditions, the latency of the light-evoked cation current in RBCs of the transgenic mice was significantly shorter compared to wild-type mice. About 10% of the transgenic mice had one eye undeveloped, and the percentage was significantly higher than in wild-type mice.ConclusionsThe data indicates that TRPV4 involves ocular development and is expressed and active in outer retinal neurons, and interventions of TRPV4 can variably affect visual signals in rods, cones, RBCs, and cone ON BCs.

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“…Electroretinograms. Full-field ERGs were recorded as described in the literature (32,36,37). Briefly, mice were dark adapted and anesthetized with ketamine/xylazine (90/10 mg/kg BW).…”

Section: Methodsmentioning

confidence: 99%

Retinal bioavailability and functional effects of a synthetic very-long-chain polyunsaturated fatty acid in mice

Gorusupudi

Rallabandi

et al. 2021

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

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Rare, nondietary very-long-chain polyunsaturated fatty acids (VLC-PUFAs) are uniquely found in the retina and a few other vertebrate tissues. These special fatty acids play a clinically significant role in retinal degeneration and development, but their physiological and interventional research has been hampered because pure VLC-PUFAs are scarce. We hypothesize that if Stargardt-3 or age-related macular degeneration patients were to consume an adequate amount of VLC-PUFAs that could be directly used in the retina, it may be possible to bypass the steps of lipid elongation mediated by the retina’s ELOVL4 enzyme and to delay or prevent degeneration. We report the synthesis of a VLC-PUFA (32:6 n-3) in sufficient quantity to study its bioavailability and functional benefits in the mouse retina. We acutely and chronically gavage fed wild-type mice and Elovl4 rod–cone conditional knockout mice this synthetic VLC-PUFA to understand its bioavailability and its role in visual function. VLC-PUFA-fed wild-type and Elovl4 conditional knockout mice show a significant increase in retinal VLC-PUFA levels in comparison to controls. The VLC-PUFA-fed mice also had improvement in the animals’ visual acuity and electroretinography measurements. Further studies with synthetic VLC-PUFAs will continue to expand our understanding of the physiological roles of these unique retinal lipids, particularly with respect to their potential utility for the treatment and prevention of retinal degenerative diseases.

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TRPV4 Does Not Regulate the Distal Retinal Light Response

Cited by 12 publications

References 28 publications

Polymodal TRPV1 and TRPV4 Sensors Colocalize but Do Not Functionally Interact in a Subpopulation of Mouse Retinal Ganglion Cells

Polymodal TRPV1 and TRPV4 Sensors Colocalize but Do Not Functionally Interact in a Subpopulation of Mouse Retinal Ganglion Cells

TRPV4 affects visual signals in photoreceptors and rod bipolar cells

Retinal bioavailability and functional effects of a synthetic very-long-chain polyunsaturated fatty acid in mice

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