Retina.pdf

Retina Karen Gil MD, MHSN Retinal Development Retina Neural Retina Development Between weeks 4 to 6 cells in the inner layer of the optic cup (neural retina) proliferate and two zones are evident Outer layer of the optic cup form the RPE 2.5 months transient layer of Chievitz * separates inner from...

Retina Karen Gil MD, MHSN Retinal Development Retina Neural Retina Development Between weeks 4 to 6 cells in the inner layer of the optic cup (neural retina) proliferate and two zones are evident Outer layer of the optic cup form the RPE 2.5 months transient layer of Chievitz * separates inner from outer neuroblastic layers of primitive retina Innermost cells will differentiate into ganglion, amacrine and Müller cells Outermost cells will differentiate in photoreceptors, horizontal and bipolar cells As retinal cells continue developing the transient layer of Chievitz probably becomes a part of the inner plexiform layer Neural Retina Development 4.5 months retinal lamination essentially is complete Photoreceptors outer segment are not yet present only inner segment 5.5 months ganglion cells have thinned out to one to two layers (except macular area) Inner nuclear layer has develop completely, include: amacrine, Müller, bipolar and horizontal cells Neural Retina Development Newborn retina has adult configuration Outer plexiform layer is thinner, but line of synapses is established * Rod and cone inner and outer segments are fully developed, and tips of outer segments contact pigment epithelium Normal retinal vascular development begins at the optic disk at about 16 weeks' gestation Angiogenesis then proceeds to extend the retinal vasculature to the periphery by 40 week in utero In premature babies, retinal vascularization completes outside the uterus * Macula Development Early in gestation it may be differentiated by an increase in ganglion cells in this macula area The cone inner fibers elongate and adopt an oblique orientation as synapse with the cells of the inner nuclear layer forming the outer plexiform layer of Henle * * Only cones develop (taller and thinner) in the macula, no rods are present Macular development continues for a few months after birth and may be dependent on a light stimulus Retina Innermost layer of the eye Neural layer Its where light energy is transformed into a neural sign Extends form the edge of the optic disc to the ora serrata Derived form the neural ectoderm Retina Laminar appearance 10 layers – – – – – – – – – – Retinal Pigment Epithelium Photoreceptor Layer Outer Limiting Membrane Outer Nuclear Layer Outer Plexiform Layer Inner Nuclear Layer Inner Plexiform Layer Ganglion Cell Layer Nerve Fiber Layer Internal Limiting Membrane Retina Retinal Pigment Epithelium Single layer of pigmented cells Apical side faces the retina Basal side lies adjacent to his basal membrane that is shared by the Bruch’s membrane RPE cells contain many organelles – – – – – – Smooth and rough ER Golgi apparatus Lysosomes Mitochondria Phagosomes Pigment cells Melanosomes Lipofuscin (from phagocytosis) Retinal pigment epithelium (RPE) contains numerous elongated melanin granules that are aggregated in the apical portion of the cell, where the microvilli extend from the surface toward the outer segments of the rod and cone cells. The retina pigment epithelial cells contain numerous mitochondria and phagosomes. The arrow indicates the location of the junction complex between two adjacent cells (Ross et al. 2003) Retinal Pigment Epithelium FIGURE 1-31 ( A ) Diagram summarizing the main ultrastructural features of the retinal pigment epithelium (RPE). ( B ) Transmission electron micrograph of human RPE layer: CC, choriocapillaris; BM, Bruch's membrane. ( C ) Scanning electron micrograph of the apical surface of the retinal pigment epithelium. Note the hexagonal shape and the ovoid melanin granules, only visible because of post-mortem-induced disruption of the apical cell membrane. Original magnifications: B , × 2600; C , × 3600. (Parts B and C courtesy of D. Aitken and W.R. Lee.) https://www.clinicalkey.com/#!/content/book/3-s2.0B9780702055546000010?scrollTo=%23hl0002209 Retinal Pigment Epithelium Embryologically derived from the outer layer of the optic cup Contains a basal membrane that fuse to the Bruch’s membrane Tight connection with the choroid Loosely adherent to the retina – creates a space between the RPE and neural retina - subretinal space (area of detachments) Schematic drawing of the inner choroid and retinal pigment epithelium (RPE). The villi (a) of the RPE extend internally to enclose the outer segments (b) of the photoreceptors. The intercellular junctions are characterized by a zonula occludens (c) and a macula adherens (d). The cytoplasm of the RPE contains a nucleus (e), mitochondria (f), a Golgi apparatus (g), melanin granules (h), phagocytosed outer segment tips (i), and smooth endoplasmic reticulum (j). The plasma membrane shows basal infoldings (l) and a basal lamina (m). In addition to the RPE basal lamina, Bruch's membrane comprises inner and outer collagenous layers (o and p), an elastin layer (n), and the basal lamina (m) of the choriocapillaris. The choriocapillaris (q) has a fenestrated epithelium (r, arrows). The intercapillary zone contains collagen (s). The lumen of the capillary contains two erythrocytes. (Hogan MJ, Alvarado JA, Weddell JE: Histology of the Human Eye. Philadelphia: WB Saunders, 1971.) Retinal Pigment Epithelium Main functions: – Phagocytosis of photoreceptor outer segments – Transport of ions, water, and metabolites between the choroid and retina Photoreceptor Layer Composed of: – 120 million rods – 6 - 8 million cones Special sensory cells Contain photopigments that absorb photons of light Divided in : – Outer and Inner segment (at the photoreceptor layer) – Outer fiber and Cell body (at the outer nuclear layer) – Inner fiber and Synaptic terminal (at the outer plexiform layer) Spherule –rods Pedicle – cones Photoreceptor Layer Diagram and matching ultrastructural features of photoreceptors: rod (left-hand panel) and cone (right-hand panel). ( A ) Rod spherule. ( B ) Cilium at junction of rod inner and outer segment. ( C ) Disk lamellae in rod outer segment. ( D ) Cone pedicle with rows of synaptic ribbons or triads. ( E ) High power of triad-type synapse in a cone pedicle. ( F ) Cone outer segment and connecting cilium. ( G ) Scanning electron micrograph of human photoreceptors: C, cone; ONL, outer nuclear layer. Original magnifications: A , × 14 000; B , × 28 000; C , × 34 000; D , × 10 000; E , × 92 000; F , × 28 000; G , × 1700. Photoreceptor Layer Outer Segment Contain discs that surround the photopigment molecules Outer segment of both rods and cones contains hundreds (500-1000) of lipid bilayered discs that are surrounded by a cell membrane Photoreceptor Layer Inner Segment Contain the cell organelles Area of metabolic activity and photopigment synthesis Which are transported to the outer segment, via cilium – where are incorporated into discs Two regions: – Myoid – Elipsoid Schematic diagram of a rod cell and its spatial relationship to the retinal pigment epithelium (RPE). (bi, basal enfoldings; c, connecting cilium; d, discs; E, ellipsoid region of the inner segment; g, Golgi apparatus; m, mitochondria; M, myoid region of the inner segment; N, nucleus; pm, plasma membrane of the outer segment; RIS, rod inner segment; ROS, rod outer segment; SP, synaptic pedicle). (Fliesler SJ, Anderson RE: Chemistry and metabolism of lipids in the vertebrate retina. In Holman RT [ed]: Progress in Lipid Research. Vol. 22. Elmsford, New York: Pergamon Press, 1983:1–52) Photoreceptor Layer Inner Segment Myoid – Inner layer – Location of protein synthesis – Contains: RER, Golgi Elipsoid – Outer layer paced with mitochondria – ATP production Photoreceptors Layer Photoreceptors contains hundreds of disc Each disc contains thousands of photopigment molecules (Rhodopsin and Iodopsin) Responsible for the light absorption Photoreceptors Layer Rods Used for scotopic vision Detects objects at low levels of illumination Density is greatest – About 5 mm concentrically form the fovea in an area known as the rod ring Rod disc contain rhodopsin – Absorbs protons maximally at 507nm – Does not detect color Photoreceptors Layer Photoreceptors Layer Cones Used for photopic vision Contains three different pigment molecules Each pigment molecule is activated by the absorption of light in a specific range in the color spectrum Blue (420nm) Green (531nm) Red (588nm) Outer (External) Limiting Membrane Barrier Is not truly a membrane Do not contain cells Band of desmosomal attachments (zonula adherents) between – Müller cells and the inner segments of photoreceptors Function – Provides structure and act as a barrier for large metabolites The external limiting membrane is formed by continuous bands of intermediate junctions (zonulae adherentes) seen here in meridional section. The inner segments (I) of the photoreceptors are linked to Müller cell processes (M) by the intermediate junctions (arrowheads). Bar = 0.5 μm. (Hogan MJ, Alvarado JA, Weddell JE: Histology of the Human Eye. Philadelphia: WB Saunders, 1971.) Outer Nuclear Layer Contains cell bodies of Rodes and Cones Outer Plexiform Layer Area where rod spherules and cone pedicles synapse with the dendrites of bipolar and horizontal cells At the macular area is known as Henle’s fiber layer Is the only layer that receives blood supply form the choroid and retina (CRA) Outer Plexiform Layer The first synapse in the visual pathway occurs here between first and second order neurons Wide external band composed of inner fibers of rods and cones and a narrower inner band consisting of synapses between photoreceptor cells and cells from the inner nuclear layer (horizontal and bipolar cells) Outer Plexiform Layer Rod spherules and cone pedicles synapse with bipolar cell dendrites Each rod spherule can synapse with 1 to 4 bipolar cells Rods only use one type of bipolar cell Cone pedicles are larger than the rod spherule Horizontal cell processes synapse with bipolar dendrites and contact other horizontal processes via gap junctions Schematic representation of rod spherules and cone pedicles with associated synapses. Rod bipolar cells, a midget cone bipolar cell, and a horizontal cell form invaginating synapses with the rods and cones. A flat cone bipolar cell forms flat synapses onto the cone pedicles. Gap junctions are also present between the rod spherules and cone pedicles. (Hogan MJ, Alvarado JA, Weddell JE. Histology of the Human Eye. Philadelphia: WB Saunders, 1971.) Outer Plexiform Layer Inner Nuclear Layer Contains the cell bodies of – – – – – Horizontal cells Bipolar cells Amacrine cells Müller cells Interplexiform cells Horizontal cells synapse with photoreceptors, bipolar and other horizontal cells Inner Nuclear Layer Horizontal cells synapse with photoreceptors in a triad form Horizontal cells modify the information that reaches the bipolar cells by providing lateral inhibition Playing a role in the complex process of visual integration Inner Plexiform Layer Location of synapse between second and third order neurons in visual pathway Layer where bipolar, amacrine and ganglion cells form connections Ganglion dendrites synapse with bipolar axons Inner Plexiform Layer Synapses between ganglion dendrites and bipolar axons are modified by amacrine cells In this layer begin the processing of motion detection and changes in brightness, as recognition of contrast and hue Bipolar cells and amacrine cells have opposite effects on ganglion cells – Bipolar cells increase stimulation of ganglion cells – Amacrine cells decrease stimulation of ganglion cells Schematic drawing of the synaptic interactions in the inner plexiform layer. A, B, and C depict bipolar synapses. D, E, and F represent amacrine cell contacts with bipolar and ganglion cells. Note ribbon-containing synapses formed by the bipolar cells. (Hogan MJ, Alvarado JA, Weddell JE: Histology of the Human Eye. Philadelphia: WB Saunders, 1971.) Ganglion Cell Layer Layer where ganglion cell bodies are located 1 to 2 layers thick In the macular area increase to 4 to 7 layers Every ganglion cell has a single axon Each axon terminates in the LGN Ganglion Cell Layer Ganglion Cell Layer 18 different types of ganglion cells Two broad categories: – P-cells – M-cells Ganglion Cell Layer P- cells – Parvocellular cells – Small diameter axons – Sensitive to color and fine detail – More common than M-cells – Project to the parvocellular layer of the LGN – The most common are the Midget ganglion cells Have a single dendrite (in the fovea) that synapses with one midget bipolar cell Allow information to be carried Ganglion Cell Layer M- cells – Magnocellular cells – Larger diameter axons – Sensitive to dim changes in illumination – Project to the magnocellular layer of the LGN Nerve Fiber Layer Axons of ganglion cells which collectively form the optic nerve Thickest at the optic nerve head margin (most superiorly and inferiorly) where a large proportion of axons enter the nerve Nerve Fiber Layer Not present in the fovea Papillomacular bundleNFL fibers that extend form the macula to the optic disc Internal Limiting Membrane Innermost boundary of the retina Comprised of footplates of Müller’s cells (covered by a basement membrane) bound to vitreous humor fibrils Present over the macula Absent over optic disc where astrocytes replace the Müller cells here Neuroglial Cells Cells that provide structure, support and protection to the retina No role in signal processing Neuroglial cells: – Müller cells – Microglial cells – Astrocytes Schematic drawing of a meridional section of the neurosensory retina and retinal pigment epithelium (RPE). ILM, inner limiting membrane; NFL, nerve fiber layer; G, ganglion cell; IPL, inner plexiform layer; A, amacrine cell; INL, inner nuclear layer; B, bipolar cell; M, Müller cell; H, horizontal cell; OPL, outer plexiform layer; ONL, outer nuclear layer; C, cone; R, rod; ELM, external limiting membrane; Br M, Bruch's membrane. (Modified from Dowling JE: Organization of vertebrate retinas. Invest Ophthalmol 9:655, 1970.) Neuroglial Cells Müller cells Most common Extend from ELM to ILM Not found within photoreceptor layer Structural function Provide nutrients to the retina, role in glycogen metabolism Most Müller cell bodies are located at the INL Some bodies are located in the ganglion layer ( A ) Micrograph of a horseradish peroxidase (HRP) filled Müller cell in the rabbit retina. The dark band at the top of the micrograph is composed of Müller cell endfeet and the labelled axons of ganglion cells in the nerve fibre layer. The Müller cells possess side-processes that form different strata in the inner plexiform and they send numerous processes to wrap around the somata of photoreceptors: NFL, nerve fibre layer; GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; IS, inner segments. ( B ) Diagram of the shape and position of a Müller cell: RPE, retinal pigment epithelium. ( C ) Morphology of a Müller cell (MC) within the outer nuclear layer. Note the intracytoplasmic microfilaments. ( D ) Microglial cells (specialized macrophages) in a retinal whole mount from a transgenic mouse in which eGFP is expressed alongside the locus for the chemokine receptor CX 3 CR1. All microglia in these animals express CX 3 CR1 and thus appear fluorescent green in confocal microscopy. ( E ) 3D-rendered retinal microglial network in a retinal wholemount in which retinal vessels have been highlighted (red) by perfusion of a vascular dye. Original magnifications: A , bar 10 mm; B , × 4400; C , × 200. (Part A courtesy of Dr. S. Robinson.) Neuroglial Cells Microglial cells Phagocytic cells Respond to inflammation and/or injury Found in all layers of the retina Neuroglial Cells Astrocytes Star shaped Most concentration found in the inner layers of the retina Fibrous cells Provide structure to nerve fibers and capillaries ( A ) Scanning electron micrograph (viewed from the vitreous aspect) of astrocytes (As) surrounding nerve fibre bundles (NFB) in the inner retina (the inner limiting membrane has been removed to expose the underlying nerve fibre layer). ( B ) Double-colour immunofluorescence illustrating the relations of astrocytes shown with an antibody to glial acidic fibrillary protein (GFAP) (red) and lectin-stained vessels (pale green). Vn, retinal vein; C, capillaries. Original magnifications: A , × 1500; B , × 150. (Part B courtesy of Dr T. Chan-Ling.) Neuroglial Cells Retinal Blood Supply Outer 5 layers receive blood supply form the choroid (short posterior ciliary arteries) Inner 5 layers receive blood supply from the CRA The OPL receives blood supply form both Podesta's scheme of the retinal vasculature demonstrates a speculative bilevel capillary arrangement, with an even-depth distribution of postarteriolar and prevenular capillaries. There is no vasculature between the inner nuclear layer and the choriocapillaris. Retinal vein shows how the major vessels lie immediately beneath and elevate the internal limiting membrane (open arrow). 1, inner limiting membrane; 2, nerve fiber layer; 3, ganglionic layer; 4, inner plexiform layer; 5, inner nuclear layer; 6, outer plexiform layer; 7, outer nuclear layer; 8, external limiting membrane; 9, layer of photoreceptor inner and outer segments; 10, pigmented epithelium; 11, choriocapillaris; 12, choroid. (Bargmann W: Histologie und mikroskopische Anatomie des Menschen, 6th ed. Stuttgart: Georg Thieme Verlag, 1967) Retinal Blood Supply Diagrams of the retinal blood supply. ( A ) The diagram illustrates the manner in which the central retinal artery obtains access to the optic nerve after branching from the ophthalmic artery. ( B ) The levels of the retinal capillary networks. ( C ) High-power diagram illustrating the components of a retinal (or brain) vessel wall that contribute to the blood–retinal (or blood–brain) barrier. From the lumen outwards these are the vascular endothelial cells (EC, pale orange), basal lamina (green) and the glia limitans composed of astrocyte foot processes (A). Note the position of the perivascular microglia (MG), perivascular macrophages (PVM) and pericytes (P). ( D ) Electron micrograph of a retinal capillary. Note the thickened basal lamina (arrows) and pericyte processes (P) surrounding the endothelial cell. Original magnification: × 6000. (Part C from McMenamin and Forrester, 1999.) https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780702055546000010?scrollTo=%23hl0002209 Retinal Blood Supply CRA forms two capillary networks – One in the INL (deep capillary network) – One in the NFL (superficial capillary network) Cilioretinal Artery – Nourishes the macula – Present in 15-20% of the population – Artery is branch of the choriocapillaris (SPCA) – If its present in a CRAO occlusion allows the macula to be spared Regions of the Retina Two regions: – Peripheral Detects gross form and motion Rods dominate – Central Specialized for visual acuity Rich in cones Has more ganglion cells per area Small portion of the retina ( A ) Wide-field photograph of the normal human fundus: F, fovea; OD, optic disk; M, macular vessels; STV and STA, superior temporal vein and artery; ITV and ITA, inferior temporal vein and artery; INV and INA, inferior nasal vein and artery; SNV and SNA, superior nasal vein and artery. ( B ), Multispectral digital ophthalmoscopic image of retinal and choroidal circulations. This new technique captures high-resolution image data through the retinal and subretinal layers and hence shows the larger vessels of the choroidal circulation. It both expands the examination wavelength range to include image data from invisible wavelengths of light and also generates the probe wavelengths to separate specific spectral regions for enhanced visibility and discrimination. No intravascular contrast is used in this method of visualizing the fundus. (Part A courtesy of C. Barry; Part B, courtesy of Annedis (Canada).) Central Retina Macula Lutea Dark, pigmented region in the posterior pole Responsible for seeing color and detail Contain two major xanthophyll pigments (yellow hue) – Lutein – Zeaxanthin this pigments are located throughout the retina, but the greatest concentration is in the macula Apparently act as filters absorbing short wavelength visible light to reduce chromatic aberration Also have suggest of an antioxidant effect, protective role against UVR damage Macula Lutea Occupies an area approximately 5.5 mm in diameter Entire macula region consists in: – Fovea – Parafovea – Perifovea Macula Lutea Is approximately 5.5 mm in diameter Its center is approximately 3.5 mm lateral to the edge of the disc and approximately 1mm inferior to the center of the disc Choroidal capillary bed is also thicker The pigment epithelial cells are taller and contain more pigment Macula Lutea Fovea Is a 1.5mm diameter circle Specialized for discrimination of detail and color vision The curved wall of the depression is known as clivus, gradually slopes to the floor that is the foveola Capillary free zone of 0.4 to 0.5 mm in diameter (foveal avascular zone) – Allow light pass unobstructed into the photoreceptor outer segment Macula Lutea Foveola Shallow depression in the center (retinal neurons are displaced living only cones in the center) foveola Diameter is about 0.35 mm Highest concentration of cones (199,000 to 300,000 per square millimeter) Area of best visual acuity No rods within the central 1 degree of the foveola Macula Lutea Foveola No bipolar and ganglion cells in the foveola Retinal layers in the foveola – – – – – – RPE Photoreceptor layer OLM ONL Henle’s fiber layer ILM No NFL in the fovea or foveola Magnification of the retina, showing the slope or clivus (CL) meeting the floor of the foveola (F). The junction (arrows) marks the termination of the inner nuclear layer (IN) and of the retinal capillaries (astericks). The ganglion cells (G) terminate approximately 30 μm before the inner layer. The internal limiting membrane continues uninterrupted. HL, Henle's fibre layer; P, photoreceptors of retina. Photomicrograph, original magnification ×485. (From Tripathi RC, Tripathi BJ. In: Davson H, ed. The Eye. Academic Press, 1984, with permission) Macula Lutea Foveola Henle’s fiber layer – Contains longer axons of photoreceptors – Oblique course to reach the displaced bipolar and horizontal cells – Region of the OPL Macula Parafovea 0.5 mm zone that surround fovea Contains largest accumulation of retinal bipolar and ganglion cells Inner nuclear layer can be 12 cells tick and the ganglion cell layer 7 cells tick Macula Lutea Perifovea 1.5mm that surrounds parafovea Ganglion cell layer is 4 cells thick and ends at the periphery with one cell tick Rod density begins to increase around 1.2 to 1.7mm from fovea The fibers of Henle’s layer revert to the usual orientation of the OPL Peripheral Retina Rods disappear and are replaced by malformed cones Nuclear layers merge with the plexiform layers Neural retina becomes a single layer of irregular columnar cells that continue as the nonpigmented epithelium of the ciliary body RPE continuous with the outer pigmented epithelium of the ciliary body Peripheral Retina Few blood vessels Ora serrata is the peripheral termination of the retina Firm attachment between the retina and vitreous Pars plana adjoining the retina at the ora serrata: 1, peripheral cystic retina; 2, ora serrata; 3, nonpigmented pars plana epithelium; 4, choroid; 5, sclera (× 225, KEI 8982B). Retinal Function Light passes through most of the retinal layers before reaching and stimulating the photoreceptor outer segment discs 128 million of photoreceptors, 35 million of bipolar cells and 1.5 million of ganglion cells receive the neural message and the info pass tough the optic nerve to the visual pathway