Topic
Outer nuclear layer
About: Outer nuclear layer is a research topic. Over the lifetime, 1422 publications have been published within this topic receiving 54434 citations.
Papers published on a yearly basis
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Papers
TL;DR: It is shown that donor cells can integrate into the adult or degenerating retina if they are taken from the developing retina at a time coincident with the peak of rod genesis, and the ontogenetic stage of donor cells for successful rod photoreceptor transplantation is defined.
Abstract: Photoreceptor loss causes irreversible blindness in many retinal diseases. Repair of such damage by cell transplantation is one of the most feasible types of central nervous system repair; photoreceptor degeneration initially leaves the inner retinal circuitry intact and new photoreceptors need only make single, short synaptic connections to contribute to the retinotopic map. So far, brain- and retina-derived stem cells transplanted into adult retina have shown little evidence of being able to integrate into the outer nuclear layer and differentiate into new photoreceptors(1-4). Furthermore, there has been no demonstration that transplanted cells form functional synaptic connections with other neurons in the recipient retina or restore visual function. This might be because the mature mammalian retina lacks the ability to accept and incorporate stem cells or to promote photoreceptor differentiation. We hypothesized that committed progenitor or precursor cells at later ontogenetic stages might have a higher probability of success upon transplantation. Here we show that donor cells can integrate into the adult or degenerating retina if they are taken from the developing retina at a time coincident with the peak of rod genesis(5). These transplanted cells integrate, differentiate into rod photoreceptors, form synaptic connections and improve visual function. Furthermore, we use genetically tagged postmitotic rod precursors expressing the transcription factor Nrl (ref. 6) ( neural retina leucine zipper) to show that successfully integrated rod photoreceptors are derived only from immature post-mitotic rod precursors and not from proliferating progenitor or stem cells. These findings define the ontogenetic stage of donor cells for successful rod photoreceptor transplantation.
1,118 citations
TL;DR: By electron microscopy, cones in the mouse retina meet virtually every morphological criterion of mammalian cones.
Abstract: Rods and cones of the C57BL/6J mouse retina have been examined by light and electron microscopy to distinguish the structural features of the two photoreceptor types. By light microscopy, cone nuclei are conspicuously different from rod nuclei in 1-2 micrometer plastic sections. Cone nuclei have an irregularly shaped clump of heterochromatin that appears in single sections to be one to three clumps, whereas rod nuclei are more densely stained and have one large, central clump of heterochromatin. Cone nuclei make up approximately 3% of the photoreceptor nuclei in both the central and peripheral retina at all ages examined up to 267 days. Cone nuclei are confined to the outer half of the outer nuclear layer, and more than 50% of the cone nuclei lie adjacent to the outer limiting membrane. By electron microscopy, cones in the mouse retina meet virtually every morphological criterion of mammalian cones. The outer segments are conically shaped. Many, if not all of the outer segment discs are continuous with the outer plasma membrane, whereas almost all of the rod discs are not. Cone outer segments are only about half the length of the rod outer segments, and they are contacted by long, villous pigment epithelial cell processes. The cone inner segment diameter is greater than the outer segment diameter, and the accumulation of mitochondria present at the apical end of the inner segment forms a more conspicuous ellipsoid than in rods. The internal fiber or axon of the cone is larger in diameter than that of the rod, and it terminates in a large synaptic pedicle with multiple ribbon synapses, whereas the rod terminal is a smaller spherule with only a single ribbon synaptic complex.
726 citations
TL;DR: Activated microglia may be a missing link in understanding why initial rod cell death in the human diseases RP, L-ORD, and AMD leads to death of the cones that are critical for high acuity daytime vision.
582 citations
TL;DR: The results indicate that cone photoreceptors throughout the retina have the potential to follow a default S-cone pathway and reveal an essential role for Trβ2 in the commitment to an M-cone identity, and raise the possibility that Thrb mutations may be associated with human cone disorders.
Abstract: Color vision is facilitated by distinct populations of cone photoreceptors in the retina. In rodents, cones expressing different opsin photopigments are sensitive to middle (M, 'green') and short (S, 'blue') wavelengths, and are differentially distributed across the retina. The mechanisms that control which opsin is expressed in a particular cone are poorly understood, but previous in vitro studies implicated thyroid hormone in cone differentiation. Thyroid hormone receptor beta 2 (TR beta 2) is a ligand-activated transcription factor that is expressed in the outer nuclear layer of the embryonic retina. Here we delete Thrb (encoding Tr beta 2) in mice, causing the selective loss of M-cones and a concomitant increase in S-opsin immunoreactive cones. Moreover, the gradient of cone distribution is disturbed, with S-cones becoming widespread across the retina. The results indicate that cone photoreceptors throughout the retina have the potential to follow a default S-cone pathway and reveal an essential role for Tr beta 2 in the commitment to an M-cone identity. Our findings raise the possibility that Thrb mutations may be associated with human cone disorders.
569 citations
TL;DR: It is suggested that genetically regulated cell death serves to fine‐tune neuronal networks during the terminal stages of development and possible mechanisms resulting in cell degeneration are discussed.
Abstract: A reproducible pattern of cell death associated with differentiation of the retina in mice was analyzed quantitatively by microscopy. Cell death occurs primarily during the first 2 weeks after birth and is essentially complete by the end of the third week. Death of individual cells involves nuclear condensation and pyknosis (apoptosis), followed by phagocytosis of the cellular remains by adjacent cells or motile phagocytes. From birth through 4 days, an increasing incidence of cell death is observed among ventricular cells. Ganglion cell degeneration is prominent during the first 11 days, peaking on days 2-5. Many presumptive amacrine cells die within the inner plexiform and inner nuclear layers, particularly between 3 and 8 days. Among adjoining bipolar and Muller cells, degeneration reaches a peak at 8-11 days. On day 5, formation of the outer plexiform layer separates the rods into two groups. Rod nuclei situated on the inner side of that layer immediately move across it to enter the outer nuclear layer, but numerous cells die during nuclear migration. Sporadic death of rods continues during the following 2 weeks. Cell death associated with cell differentiation (histogenetic death) is considered to represent a normal developmental process. Possible mechanisms resulting in cell degeneration are discussed. It is suggested that genetically regulated cell death serves to fine-tune neuronal networks during the terminal stages of development.
568 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2026 | 1 |
| 2025 | 12 |
| 2024 | 24 |
| 2023 | 72 |
| 2022 | 116 |
| 2021 | 79 |