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Development (Cambridge, England) Jun 2020The cochlea, a coiled structure located in the ventral region of the inner ear, acts as the primary structure for the perception of sound. Along the length of the... (Review)
Review
The cochlea, a coiled structure located in the ventral region of the inner ear, acts as the primary structure for the perception of sound. Along the length of the cochlear spiral is the organ of Corti, a highly derived and rigorously patterned sensory epithelium that acts to convert auditory stimuli into neural impulses. The development of the organ of Corti requires a series of inductive events that specify unique cellular characteristics and axial identities along its three major axes. Here, we review recent studies of the cellular and molecular processes regulating several aspects of cochlear development, such as axial patterning, cochlear outgrowth and cellular differentiation. We highlight how the precise coordination of multiple signaling pathways is required for the successful formation of a complete organ of Corti.
Topics: Animals; Auditory Perception; Cell Differentiation; Cochlea; Hair Cells, Auditory; Mitosis; Organ of Corti; SOXB1 Transcription Factors; Signal Transduction
PubMed: 32571852
DOI: 10.1242/dev.162263 -
Medecine Sciences : M/S 2020The neuroretina is a functional unit of the central nervous system that converts a light signal into a nerve impulse. Of neuroectodermal origin, derived from the... (Review)
Review
The neuroretina is a functional unit of the central nervous system that converts a light signal into a nerve impulse. Of neuroectodermal origin, derived from the diencephalon, the neuroretina is a layered tissue composed of six types of neuronal cells (two types of photoreceptors: cones and rods, horizontal, bipolar, amacrine and ganglion cells) and three types of glial cells (Müller glial cells, astrocytes and microglial cells). The neuroretina lays on the retinal pigmentary epithelium, that together form the retina. The existence of the internal and external blood-retinal barriers and intra-retinal junctions reflects the fineness of regulation of the retinal exchanges with the circulation and within the retina itself. The central zone of the human retina, which is highly specialized for visual acuity, has anatomical specificities. Recent imaging methods make it possible now to enrich our knowledge of the anatomical and functional characteristics of the retina, which are still imperfectly described.
Topics: Animals; Choroid; Humans; Neuroglia; Retina; Retinal Cone Photoreceptor Cells; Retinal Pigment Epithelium; Retinal Rod Photoreceptor Cells; Retinal Vessels
PubMed: 32614310
DOI: 10.1051/medsci/2020094 -
Current Opinion in Ophthalmology Mar 2022Biomechanics is an important aspect of the complex family of diseases known as the glaucomas. Here, we review recent studies of biomechanics in glaucoma. (Review)
Review
PURPOSE OF REVIEW
Biomechanics is an important aspect of the complex family of diseases known as the glaucomas. Here, we review recent studies of biomechanics in glaucoma.
RECENT FINDINGS
Several tissues have direct and/or indirect biomechanical roles in various forms of glaucoma, including the trabecular meshwork, cornea, peripapillary sclera, optic nerve head/sheath, and iris. Multiple mechanosensory mechanisms and signaling pathways continue to be identified in both the trabecular meshwork and optic nerve head. Further, the recent literature describes a variety of approaches for investigating the role of tissue biomechanics as a risk factor for glaucoma, including pathological stiffening of the trabecular meshwork, peripapillary scleral structural changes, and remodeling of the optic nerve head. Finally, there have been advances in incorporating biomechanical information in glaucoma prognoses, including corneal biomechanical parameters and iridial mechanical properties in angle-closure glaucoma.
SUMMARY
Biomechanics remains an active aspect of glaucoma research, with activity in both basic science and clinical translation. However, the role of biomechanics in glaucoma remains incompletely understood. Therefore, further studies are indicated to identify novel therapeutic approaches that leverage biomechanics. Importantly, clinical translation of appropriate assays of tissue biomechanical properties in glaucoma is also needed.
Topics: Biomechanical Phenomena; Glaucoma; Humans; Intraocular Pressure; Optic Disk; Sclera; Trabecular Meshwork
PubMed: 34954731
DOI: 10.1097/ICU.0000000000000829 -
Annual Review of Vision Science Sep 2021The outer retina is nourished from the choroid, a capillary bed just inside the sclera. O, glucose, and other nutrients diffuse out of the choroid and then filter... (Review)
Review
The outer retina is nourished from the choroid, a capillary bed just inside the sclera. O, glucose, and other nutrients diffuse out of the choroid and then filter through a monolayer of retinal pigment epithelium (RPE) cells to fuel the retina. Recent studies of energy metabolism have revealed striking differences between retinas and RPE cells in the ways that they extract energy from fuels. The purpose of this review is to suggest and evaluate the hypothesis that the retina and RPE have complementary metabolic roles that make them depend on each other for survival and for their abilities to perform essential and specialized functions.
Topics: Choroid; Energy Metabolism; Retina; Retinal Pigment Epithelium
PubMed: 34102066
DOI: 10.1146/annurev-vision-100419-115156 -
Molecules (Basel, Switzerland) Aug 2022Age-related macular degeneration (AMD) was described for the first time in the 1840s and is currently the leading cause of blindness for patients over 65 years in... (Review)
Review
Age-related macular degeneration (AMD) was described for the first time in the 1840s and is currently the leading cause of blindness for patients over 65 years in Western Countries. This disease impacts the eye's posterior segment and damages the macula, a retina section with high levels of photoreceptor cells and responsible for the central vision. Advanced AMD stages are divided into the atrophic (dry) form and the exudative (wet) form. Atrophic AMD consists in the progressive atrophy of the retinal pigment epithelium (RPE) and the outer retinal layers, while the exudative form results in the anarchic invasion by choroidal neo-vessels of RPE and the retina. This invasion is responsible for fluid accumulation in the intra/sub-retinal spaces and for a progressive dysfunction of the photoreceptor cells. To date, the few existing anti-AMD therapies may only delay or suspend its progression, without providing cure to patients. However, in the last decade, an outstanding number of research programs targeting its different aspects have been initiated by academics and industrials. This review aims to bring together the most recent advances and insights into the mechanisms underlying AMD pathogenicity and disease evolution, and to highlight the current hypotheses towards the development of new treatments, i.e., symptomatic vs. curative. The therapeutic options and drugs proposed to tackle these mechanisms are analyzed and critically compared. A particular emphasis has been given to the therapeutic agents currently tested in clinical trials, whose results have been carefully collected and discussed whenever possible.
Topics: Aged; Aging; Humans; Macular Degeneration; Photoreceptor Cells; Retina; Retinal Pigment Epithelium
PubMed: 36014339
DOI: 10.3390/molecules27165089 -
Nature Mar 2022Interoception, the ability to timely and precisely sense changes inside the body, is critical for survival. Vagal sensory neurons (VSNs) form an important body-to-brain...
Interoception, the ability to timely and precisely sense changes inside the body, is critical for survival. Vagal sensory neurons (VSNs) form an important body-to-brain connection, navigating visceral organs along the rostral-caudal axis of the body and crossing the surface-lumen axis of organs into appropriate tissue layers. The brain can discriminate numerous body signals through VSNs, but the underlying coding strategy remains poorly understood. Here we show that VSNs code visceral organ, tissue layer and stimulus modality-three key features of an interoceptive signal-in different dimensions. Large-scale single-cell profiling of VSNs from seven major organs in mice using multiplexed projection barcodes reveals a 'visceral organ' dimension composed of differentially expressed gene modules that code organs along the body's rostral-caudal axis. We discover another 'tissue layer' dimension with gene modules that code the locations of VSN endings along the surface-lumen axis of organs. Using calcium-imaging-guided spatial transcriptomics, we show that VSNs are organized into functional units to sense similar stimuli across organs and tissue layers; this constitutes a third 'stimulus modality' dimension. The three independent feature-coding dimensions together specify many parallel VSN pathways in a combinatorial manner and facilitate the complex projection of VSNs in the brainstem. Our study highlights a multidimensional coding architecture of the mammalian vagal interoceptive system for effective signal communication.
Topics: Animals; Brain; Calcium; Mammals; Mice; Perception; Psychophysiology; Sensory Receptor Cells; Vagus Nerve; Vomeronasal Organ
PubMed: 35296859
DOI: 10.1038/s41586-022-04515-5 -
Progress in Retinal and Eye Research Jul 2021Diabetic retinopathy (DR) is a leading cause of blindness. It has long been regarded as vascular disease, but work in the past years has shown abnormalities also in the... (Review)
Review
Diabetic retinopathy (DR) is a leading cause of blindness. It has long been regarded as vascular disease, but work in the past years has shown abnormalities also in the neural retina. Unfortunately, research on the vascular and neural abnormalities have remained largely separate, instead of being integrated into a comprehensive view of DR that includes both the neural and vascular components. Recent evidence suggests that the most predominant neural cell in the retina (photoreceptors) and the adjacent retinal pigment epithelium (RPE) play an important role in the development of vascular lesions characteristic of DR. This review summarizes evidence that the outer retina is altered in diabetes, and that photoreceptors and RPE contribute to retinal vascular alterations in the early stages of the retinopathy. The possible molecular mechanisms by which cells of the outer retina might contribute to retinal vascular damage in diabetes also are discussed. Diabetes-induced alterations in the outer retina represent a novel therapeutic target to inhibit DR.
Topics: Diabetes Mellitus; Diabetic Retinopathy; Humans; Photoreceptor Cells; Retina; Retinal Pigment Epithelium
PubMed: 33188897
DOI: 10.1016/j.preteyeres.2020.100919 -
Progress in Retinal and Eye Research Jul 2021Gene expression provides valuable insight into cell function. As such, vision researchers have frequently employed gene expression studies to better understand retinal... (Review)
Review
Gene expression provides valuable insight into cell function. As such, vision researchers have frequently employed gene expression studies to better understand retinal physiology and disease. With the advent of single-cell RNA sequencing, expression experiments provide an unparalleled resolution of information. Instead of studying aggregated gene expression across all cells in a heterogenous tissue, single-cell technology maps RNA to an individual cell, which facilitates grouping of retinal and choroidal cell types for further study. Single-cell RNA sequencing has been quickly adopted by both basic and translational vision researchers, and single-cell level gene expression has been studied in the visual systems of animal models, retinal organoids, and primary human retina, RPE, and choroid. These experiments have generated detailed atlases of gene expression and identified new retinal cell types. Likewise, single-cell RNA sequencing investigations have characterized how gene expression changes in the setting of many retinal diseases, including how choroidal endothelial cells are altered in age-related macular degeneration. In addition, this technology has allowed vision researchers to discover drivers of retinal development and model rare retinal diseases with induced pluripotent stem cells. In this review, we will overview the growing number of single-cell RNA sequencing studies in the field of vision research. We will summarize experimental considerations for designing single-cell RNA sequencing experiments and highlight important advancements in retinal, RPE, choroidal, and retinal organoid biology driven by this technology. Finally, we generalize these findings to genes involved in retinal degeneration and outline the future of single-cell expression experiments in studying retinal disease.
Topics: Animals; Choroid; Endothelial Cells; Humans; Retina; Retinal Degeneration; Retinal Pigment Epithelium; Sequence Analysis, RNA
PubMed: 33383180
DOI: 10.1016/j.preteyeres.2020.100934 -
Proceedings of the National Academy of... Nov 2019The human retinal pigment epithelium (RPE) and choroid are complex tissues that provide crucial support to the retina. Disease affecting either of these supportive...
The human retinal pigment epithelium (RPE) and choroid are complex tissues that provide crucial support to the retina. Disease affecting either of these supportive tissues can lead to irreversible blindness in the setting of age-related macular degeneration. In this study, single-cell RNA sequencing was performed on macular and peripheral regions of RPE-choroid from 7 human donor eyes in 2 independent experiments. In the first experiment, total RPE/choroid preparations were evaluated and expression profiles specific to RPE and major choroidal cell populations were identified. As choroidal endothelial cells represent a minority of the total RPE/choroidal cell population but are strongly implicated in age-related macular degeneration (AMD) pathogenesis, a second single-cell RNA-sequencing experiment was performed using endothelial cells enriched by magnetic separation. In this second study, we identified gene expression signatures along the choroidal vascular tree, classifying the transcriptome of human choriocapillaris, arterial, and venous endothelial cells. We found that the choriocapillaris highly and specifically expresses the regulator of cell cycle gene (), a gene that responds to complement activation and induces apoptosis in endothelial cells. In addition, was the most up-regulated choriocapillaris gene in a donor diagnosed with AMD. These results provide a characterization of the human RPE and choriocapillaris transcriptome, offering potential insight into the mechanisms of choriocapillaris response to complement injury and choroidal vascular disease in age-related macular degeneration.
Topics: Choroid; Epithelial Cells; Epithelium; Humans; Macular Degeneration; Retina; Single-Cell Analysis; Transcriptome
PubMed: 31712411
DOI: 10.1073/pnas.1914143116 -
Progress in Retinal and Eye Research Jul 2021The optic nerve head can morphologically be differentiated into the optic disc with the lamina cribrosa as its basis, and the parapapillary region with zones alpha... (Review)
Review
The optic nerve head can morphologically be differentiated into the optic disc with the lamina cribrosa as its basis, and the parapapillary region with zones alpha (irregular pigmentation due to irregularities of the retinal pigment epithelium (RPE) and peripheral location), beta zone (complete RPE loss while Bruch's membrane (BM) is present), gamma zone (absence of BM), and delta zone (elongated and thinned peripapillary scleral flange) within gamma zone and located at the peripapillary ring. Alpha zone is present in almost all eyes. Beta zone is associated with glaucoma and may develop due to a IOP rise-dependent parapapillary up-piling of RPE. Gamma zone may develop due to a shift of the non-enlarged BM opening (BMO) in moderate myopia, while in highly myopic eyes, the BMO enlarges and a circular gamma zone and delta zone develop. The ophthalmoscopic shape and size of the optic disc is markedly influenced by a myopic shift of BMO, usually into the temporal direction, leading to a BM overhanging into the intrapapillary compartment at the nasal disc border, a secondary lack of BM in the temporal parapapillary region (leading to gamma zone in non-highly myopic eyes), and an ocular optic nerve canal running obliquely from centrally posteriorly to nasally anteriorly. In highly myopic eyes (cut-off for high myopia at approximately -8 diopters or an axial length of 26.5 mm), the optic disc area enlarges, the lamina cribrosa thus enlarges in area and decreases in thickness, and the BMO increases, leading to a circular gamma zone and delta zone in highly myopic eyes.
Topics: Bruch Membrane; Glaucoma; Humans; Myopia; Optic Disk; Sclera; Tomography, Optical Coherence
PubMed: 33309588
DOI: 10.1016/j.preteyeres.2020.100933