Synapses are fundamental information processing units that rely on voltage-gated Ca (Ca) channels to trigger Ca-dependent neurotransmitter release. Ca channels also play Ca-independent roles in other biological contexts, but whether they do so in axon terminals is unknown. Here, we addressed this unknown with respect to the requirement for Ca1.4 L-type channels for the formation of rod photoreceptor synapses in the retina. Using a mouse strain expressing a non-conducting mutant form of Ca1.4, we report that the Ca1.4 protein, but not its Ca conductance, is required for the molecular assembly of rod synapses; however, Ca1.4 Ca signals are needed for the appropriate recruitment of postsynaptic partners. Our results support a model in which presynaptic Ca channels serve both as organizers of synaptic building blocks and as sources of Ca ions in building the first synapse of the visual pathway and perhaps more broadly in the nervous system.
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http://dx.doi.org/10.7554/eLife.62184 | DOI Listing |
Invest Ophthalmol Vis Sci
January 2025
Biology and Biochemistry PhD Programs, Graduate Center, City University of New York, New York, New York, United States.
Purpose: Retinal development in the mouse continues past birth and provides a widely used model system in which photoreceptor formation can be observed and manipulated. This experimental paradigm provides opportunities for both gain-of-function and loss-of-function studies, which can be accomplished through in vivo or ex vivo plasmid delivery and electroporation. However, the cis-regulatory elements used to implement this approach have not been fully evaluated or optimized for the unique transcriptional environment of photoreceptors.
View Article and Find Full Text PDFCells
January 2025
Department of Biochemistry, School of Medicine, Wake Forest University, Winston Salem, NC 27101, USA.
Glucose-sensing ChREBP and MondoA are transcriptional factors involved in the lipogenic, inflammatory, and insulin signaling pathways implicated in metabolic disorders; however, limited ocular studies have been conducted on these proteins. We aimed to investigate the potential role of ChREBP in the pathogenesis of diabetic retinopathy (DR). We used diabetic human and mouse retinal cryosections analyzed by immunohistochemistry.
View Article and Find Full Text PDFCommun Biol
January 2025
Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA.
Rod and cone photoreceptor cells are specialized neurons responsible for transforming the information reaching the eyes in the form of photons into the language of neuronal activity. Rods are the most prevalent photoreceptor type, primarily responsible for light detection under conditions of limited illumination. Here we demonstrate that human rods have a morphological organization unique among all described species, whereby the cell soma extends alongside the light-sensitive outer segment compartment to form a structure we have termed the "accessory inner segment.
View Article and Find Full Text PDFAsia Pac J Ophthalmol (Phila)
January 2025
Rescue, Repair and Regeneration Theme, UCL Institute of Ophthalmology, London, United Kingdom. Electronic address:
Purpose: Recovery rate of rod photoreceptor sensitivity (S2 gradient) following a bleach is reduced in age-related macular degeneration (AMD) due to diminished delivery of retinol across a grossly altered Bruch's membrane. Since triterpenoid saponins are known to improve transport across Bruch's, we have assessed their possible use for reversing the visual deficits in AMD.
Design: Double-blind, placebo controlled randomised clinical trial.
Exp Eye Res
January 2025
Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India. Electronic address:
Autophagy is common in the aging retinal pigment epithelium (RPE). A dysfunctional autophagy in aged RPE is implicated in the pathogenesis of age-related macular degeneration. Aging human retina accompanies degenerative changes in photoreceptor mitochondria.
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