Retinal TRP channels: Cell-type-specific regulators of retinal homeostasis and multimodal integration

Križaj, David; Cordeiro, Soenke; Strauß, Olaf

doi:10.1016/j.preteyeres.2022.101114

Cited by 33 publications

(20 citation statements)

References 402 publications

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“…However, both c14 and c19 specifically express gramd1b , which is an RBC-specific marker in mice. In addition to these genetic signatures similar to mammalian RBCs, both c14 and c19 clusters express neurotransmitter receptor, grm6a and grm6b, and it’s downstream signaling molecules, trpm1a, trpm1b , nyx and rgs11, which are essential for mediating rod inputs in mammals 39 (Fig. S1).…”

Section: Resultsmentioning

confidence: 99%

Ancient origin of the rod bipolar cell pathway in the vertebrate retina

Hellevik,

Mardoum,

Hahn

et al. 2023

Preprint

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Vertebrates rely on rod photoreceptors for vision in low-light conditions1. Mammals have a specialized downstream circuit for rod signaling called the primary rod pathway, which comprises specific cell types and wiring patterns that are thought to be unique to this lineage2–6. Thus, it has been long assumed that the primary rod pathway evolved in mammals3, 5–7. Here, we challenge this view by demonstrating that the mammalian primary rod pathway is conserved in zebrafish, which diverged from extant mammals ∼400 million years ago. Using single-cell RNA-sequencing, we identified two bipolar cell (BC) types in zebrafish that are related to mammalian rod BCs (RBCs) of the primary rod pathway. By combining electrophysiology, histology, and ultrastructural reconstruction of the zebrafish RBCs, we found that, like mammalian RBCs8, both zebrafish RBC types connect with all rods and red-cones in their dendritic territory, and provide output largely onto amacrine cells. The wiring pattern of the amacrine cells post-synaptic to one RBC type is strikingly similar to that of mammalian RBCs, suggesting that the cell types and circuit design of the primary rod pathway have emerged before the divergence of teleost fish and amniotes (mammals, birds, reptiles). The second RBC type in zebrafish, which forms separate pathways from the first RBC type, is either lost in mammals or emerged in fish to serve yet unknown roles.Highlights-Zebrafish have two rod bipolar cell types (RBC1/2).-Synaptic connectivity of RBC1 resembles that of the mammalian RBCs.-The primary rod pathway therefore probably evolved more than 400 million years ago.-The second zebrafish RBC type, RBC2, forms a separate pathway from RBC1.

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Section: Resultsmentioning

confidence: 99%

Ancient origin of the rod bipolar cell pathway in the vertebrate retina

Hellevik,

Mardoum,

Hahn

et al. 2023

Preprint

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“…The presence of osmosensitive Ca 2+ channels and/or transporters has been predicted by swelling- and Ca 2+ -activated K + and Cl - currents in bovine, pig and huma preparations (Mitchell, Fleischhauer et al 2002, Soto, Comes et al 2004, Srinivas, Maertens et al 2004), but the source of the Ca 2+ signal has remained unknown. We focused on TRPV4 (Transient Receptor Potential Vanilloid Isoform 4) due to its prominent expression in rodent and human TM (Luo, Conwell et al 2014, Ryskamp, Frye et al 2016), roles ins ensing pressure, strain and body temperature (Ryskamp, Frye et al 2016, Yarishkin, Phuong et al 2021, Krizaj, Cordeiro et al 2023), role in TRPM4-mediated Na + influx (Yarishkin, Phuong et al 2022), AQP interactions (Jo, Ryskamp et al 2015, Mola, Sparaneo et al 2016) and sensitivity to hypotonic stimuli in other cell types (Liedtke and Friedman 2003, Hoffmann, Lambert et al 2009). TRPV4 is a tetrameric channel with the S5-S6 region forming a pore permeable to cations, and functional domains within the N- and C-termini regulating trafficking, protein-protein interactions and sensitivity to lipid and mechanical milieus.…”

Section: Introductionmentioning

confidence: 99%

Osmosensing in trabecular meshwork cells

Baumann,

Yarishkin,

Lakk

et al. 2024

Preprint

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Aqueous humor drainage from the anterior eye constitutes a key determinant of intraocular pressure (IOP) under homeostatic and pathological conditions. Swelling of the trabecular meshwork (TM) increases its flow resistance but the mechanisms that sense and transduce osmotic gradients remain poorly understood. We used optical molecular analyses, optical imaging and electrophysiology to investigate TM osmotransduction and its role in calcium and chloride homeostasis. Anisosmotic conditions elicited proportional changes in TM cell volume. Swelling, but not shrinking, evoked increases in intracellular calcium concentration [Ca2+]TM. Hypotonicity-evoked calcium signals were sensitive to HC067047, a selective blocker of TRPV4 channels, whereas the agonist GSK1016790A promoted swelling under isotonic conditions. TRPV4 inhibition partially suppressed hypotonicity-induced volume increases and reduced the magnitude of the swelling-induced membrane current, with a substantial fraction of the swelling-evoked current abrogated by Cl-channel antagonists DIDS and niflumic acid. The volume-sensing transcriptome of primary human TM cells showed expression of TRPV4, TRPM4, AQP1, and TMEMC3B genes. Cl-channel expression was dominated by ANO6 transcripts, auxiliary levels of ANO3, ANO7 and ANO10 and modest expression of LTTRC genes that encode volume-activated anion channels. Thus, TRPV4-mediated cation influx works with Cl-efflux to sense and respond to osmotic stress, potentially contributing to pathological swelling, calcium overload and intracellular signaling that could exacerbate functional disturbances in inflammatory disease and glaucoma.

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“…These channels serve as bandpass filters allowing transmission of certain types of mechanical loading pressure such as tension, stretch, shear flow, and compression at specific amplitude. Previous studies identified the expression of Piezo and TRP family channels in the cornea ( 28 ), TM ( 29 ), and retina ( 30 ), which exerts a vital impact on the regulation of inflammation, oxidative stress, cell apoptosis, and neurotransmission, etc. ( 31 ).…”

Section: Introductionmentioning

confidence: 99%

Biomechanical homeostasis in ocular diseases: A mini-review

Cheng

Ren

Wang

2023

Front. Public Health

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Diabetes mellitus-induced hyperglycemia is responsible for multiple pathological ocular alternations from vasculopathy to biomechanical dyshomeostasis. Biomechanical homeostasis is crucial to maintain the normal physiological condition of the eyes. Biomechanical features vary in eye tissues regarding different anatomical positions, tissue components, and cellular functions. The disturbance in biomechanical homeostasis may result in different ocular diseases. In this review, we provide a preliminary sketch of the latest evidence on the mechano-environment of the eyeball and its possible influencing factors, thereby underscoring the relationship between the dyshomeostasis of ocular biomechanics and common eye diseases (e.g., diabetic retinopathy, keratoconus, glaucoma, spaceflight-associated neuro-ocular syndrome, retinal vein occlusion and myopia, etc.). Together with the reported evidence, we further discuss and postulate the potential role of biomechanical homeostasis in ophthalmic pathology. Some latest strategies to investigate the biomechanical properties in ocular diseases help unveil the pathological changes at multiple scales, offering references for making new diagnostic and treatment strategies targeting mechanobiology.

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Retinal TRP channels: Cell-type-specific regulators of retinal homeostasis and multimodal integration

Cited by 33 publications

References 402 publications

Ancient origin of the rod bipolar cell pathway in the vertebrate retina

Ancient origin of the rod bipolar cell pathway in the vertebrate retina

Osmosensing in trabecular meshwork cells

Biomechanical homeostasis in ocular diseases: A mini-review

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