Molecular mechanisms underlying selective synapse formation of vertebrate retinal photoreceptor cells

Furukawa, Takahisa; Ueno, Akihiko; Omori, Yoshihiro

doi:10.1007/s00018-019-03324-w

Cited by 19 publications

(15 citation statements)

References 129 publications

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“…Thus, synapses, necessary for proper cell-to-cell communication, are critical for vision. Discussion of the complexity of PR synaptic development and function is reviewed in [306][307][308], and is beyond the scope of this review. Suffice to say that mutations in many of the components of synapses, such as presynaptic exocytotic proteins, endocytic proteins, calcium channels, postsynaptic receptors, and associated elements, must be properly organized to mediate transmission of signals, or can lead to visual problems [307].…”

Section: Category 05: Synapsementioning

confidence: 99%

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

Collin

Gogna

Chang

et al. 2020

Cells

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Inherited retinal degeneration (RD) leads to the impairment or loss of vision in millions of individuals worldwide, most frequently due to the loss of photoreceptor (PR) cells. Animal models, particularly the laboratory mouse, have been used to understand the pathogenic mechanisms that underlie PR cell loss and to explore therapies that may prevent, delay, or reverse RD. Here, we reviewed entries in the Mouse Genome Informatics and PubMed databases to compile a comprehensive list of monogenic mouse models in which PR cell loss is demonstrated. The progression of PR cell loss with postnatal age was documented in mutant alleles of genes grouped by biological function. As anticipated, a wide range in the onset and rate of cell loss was observed among the reported models. The analysis underscored relationships between RD genes and ciliary function, transcription-coupled DNA damage repair, and cellular chloride homeostasis. Comparing the mouse gene list to human RD genes identified in the RetNet database revealed that mouse models are available for 40% of the known human diseases, suggesting opportunities for future research. This work may provide insight into the molecular players and pathways through which PR degenerative disease occurs and may be useful for planning translational studies.

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Section: Category 05: Synapsementioning

confidence: 99%

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

Collin

Gogna

Chang

et al. 2020

Cells

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“…It has been suggested that the invagination of rod BC dendrites into rod spherules depends on two parallel transsynaptic bridges of the extracellular leucine-rich repeat fibronectin containing 1 (ELFN1)-mGluR6 complex 28,29 and the dystrophin-glycoprotein complex (DGC)-Pikachurin-G protein-coupled receptor 179 (GPR179) complex. [30][31][32] Here both Elfn1 −/− and Nob4 (a type of mGluR6-deficient mutant) mice exhibited defects in rod BC invagination. 28,33,34 It could then be hypothesized that mGluR6 deficiency may disrupt rod-rod BC transsynaptic adhesion.…”

Section: Discussionmentioning

confidence: 98%

“…Therefore, we cannot ignore the possible role of the DGC-Pikachurin-GPR179 bridge in mGluR6-deficient mice. 32 The perplexing connections among molecules underlying selective synapse formation remain to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Helical Fasciculation of Bipolar and Horizontal Cell Neurites for Wiring With Photoreceptors in Macaque and Mouse Retinas

Tsukamoto

Iseki²,

Omi³

2021

Invest. Ophthalmol. Vis. Sci.

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The three-dimensional configurations of rod and cone bipolar cell (BC) dendrites and horizontal cell (HC) processes outside rod and cone synaptic terminals have not been fully elucidated. We reveal how these neurites are mutually arranged to coordinate formation and maintenance of the postsynaptic complex of ribbon synapses in mouse and monkey retinas. METHODS.Serial section transmission electron microscopy was utilized to reconstruct BC and HC neurites in macaque monkey and mouse, including metabotropic glutamate receptor 6 (mGluR6)-knockout mice. RESULTS.Starting from sporadically distributed branching points, rod BC and HC neurites (B and H, respectively) took specific paths to rod spherules by gradually adjusting their mutual positions, which resulted in a closed alternating pattern of H-B-H-B neurites at the rod spherule aperture. This order corresponded to the array of elements constituting the postsynaptic complex of ribbon synapses. We identified novel helical coils of HC processes surrounding the rod BC dendrite in both mouse and macaque retinas, and these structures occurred more frequently in mGluR6-knockout than wild-type mouse retinas. Horizontal cell processes also formed hook-like protrusions that encircled cone BC and HC neurites below the cone pedicles in the macaque retina. CONCLUSIONS.Bipolar and horizontal cell neurites take specific paths to adjust their mutual positions at the rod spherule aperture. Some HC processes are helically coiled around rod BC dendrites or form hook-like protrusions around cone BC dendrites and HC processes. Loss of mGluR6 signaling may be one factor promoting unbalanced neurite growth and compensatory neurite coiling.

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“…Specific pre-and postsynaptic membrane proteins linked by specific extracellular proteins that determine target type and are essential for correct synapse formation. 16…”

Section: Synaptogenesismentioning

confidence: 99%

Coculture techniques for modeling retinal development and disease, and enabling regenerative medicine

Ghareeb

Lako

Steel

2020

Stem Cells Translational Medicine

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Stem cell‐derived retinal organoids offer the opportunity to cure retinal degeneration of wide‐ranging etiology either through the study of in vitro models or the generation of tissue for transplantation. However, despite much work in animals and several human pilot studies, satisfactory therapies have not been developed. Two major challenges for retinal regenerative medicine are (a) physical cell‐cell interactions, which are critical to graft function, are not formed and (b) the host environment does not provide suitable queues for development. Several strategies offer to improve the delivery, integration, maturation, and functionality of cell transplantation. These include minimally invasive delivery, biocompatible material vehicles, retinal cell sheets, and optogenetics. Optimizing several variables in animal models is practically difficult, limited by anatomical and disease pathology which is often different to humans, and faces regulatory and ethical challenges. High‐throughput methods are needed to experimentally optimize these variables. Retinal organoids will be important to the success of these models. In their current state, they do not incorporate a representative retinal pigment epithelium (RPE)‐photoreceptor interface nor vascular elements, which influence the neural retina phenotype directly and are known to be dysfunctional in common retinal diseases such as age‐related macular degeneration. Advanced coculture techniques, which emulate the RPE‐photoreceptor and RPE‐Bruch's‐choriocapillaris interactions, can incorporate disease‐specific, human retinal organoids and overcome these drawbacks. Herein, we review retinal coculture models of the neural retina, RPE, and choriocapillaris. We delineate the scientific need for such systems in the study of retinal organogenesis, disease modeling, and the optimization of regenerative cell therapies for retinal degeneration.

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Molecular mechanisms underlying selective synapse formation of vertebrate retinal photoreceptor cells

Cited by 19 publications

References 129 publications

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

Helical Fasciculation of Bipolar and Horizontal Cell Neurites for Wiring With Photoreceptors in Macaque and Mouse Retinas

Coculture techniques for modeling retinal development and disease, and enabling regenerative medicine

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