Uvea Development PDF

UVEA Karen Gil MD, MHSN Uvea Development Iris 3th month – Optic cup (neuroectoderm) outer layer becomes anterior iris epithelium – Optic cup inner layer forms the posterior iris epithelium – Myofilaments of the anterior epithelium proliferate into myoepithelium to form the iris sphincter muscle (neu...

UVEA Karen Gil MD, MHSN Uvea Development Iris 3th month – Optic cup (neuroectoderm) outer layer becomes anterior iris epithelium – Optic cup inner layer forms the posterior iris epithelium – Myofilaments of the anterior epithelium proliferate into myoepithelium to form the iris sphincter muscle (neuroectorerm origin -5th month) 6th month – – The dilatator muscle (neuroectodermal origin) begins to develop myofibrils form from the anterior layer of the iris epithelium – Anterior border layer form from mesenchymal cells and stroma component are from neural crest origin Uvea Development Ciliary Body 3th month – Outer layer of the optic cup become outer pigmented epithelium of the ciliary body – Inner optic cup form inner nonpigmented epithelium of the ciliary body with grows and folds 70 in number that become the ciliary processes 4th month – Neural crest form stroma and ciliary muscle Schematic diagram of the development of chamber angle and trabecular meshwork in the mouse eye between postnatal days (P) 1 and 14. A: From P1-P4, the chamber angle is occupied by a dense mass of mesenchymal cells (arrows). B: From P4-P10, chamber angle cells (solid arrows) become separated from each other by small open spaces that are partially filled with extracellular fibers, while vessels appear in the immediate adjacent sclera (open arrows). During this period, the chamber angle is level with the anterior border of the future trabecular meshwork. C: From P11-P14, the extracellular fibers in the chamber angle organize themselves into trabecular beams that become covered by trabecular meshwork cells, while the scleral vessels next to the chamber angle coalesce to Schlemm’s canal. In parallel, the peripheral margin of the anterior chamber moves posteriorly and the inner surface of the trabecular meshwork becomes exposed to the anterior chamber (AC). Re: Medina, CB: ciliary body. Chamber Angle and Uvea Development 5th month – group of neural crest cells at the peripheral posterior aspect of the cornea differentiates into the chamber angle, trabecular meshwork and Schlemm’s canal Aqueous humor production begins 4-6 months of gestation Uveal Development Optic cup divided in – Outer layer becomes: Retinal pigment epithelium (RPE) The outer pigmented ciliary body epithelium Anterior non-pigmented iris epithelium – Inner layer becomes: The neural retina Non-pigmented ciliary body epithelium Posterior pigment epithelium of the iris Optic cup layers development Outer layer Inner layer RPE- Retinal Pigment Epithelium Retina Ciliary Body Iris Anterior Segment Development Choroid Mesenchyme forms the choriocapillaris 2nd month appear the vessels Bruch’s membrane develops 4th month 5th month large and medium layer of vessels are evident (form vortex veins) Schematic diagram of ocular mesenchyme development in the mouse eye between embryonic days lens vesicle (LV) has detached from the surface epithelium (SE) and has become invaginated into the optic cup. Mesenchymal cells (ME) start to migrate into the space between the anterior epithelium of the lens vesicle and the surface ectoderm. The inner layer of the optic cup forms the neural retina (Re), the outer layer the retinal pigmented epithelium (PE). The optic cup is incompletely inferior at the so-called embryonic (choroidal) fissure (EF), where the hyaloid artery (HA) enters the optic cup. B: At E 13.5-14.5, the mesenchyme cells condense to form several flat layers that are separated from each other by a loose fibrillar extracellular matrix. In the lens (Le), the primary lens fibers elongate to close the lumen of the lens vesicle. Cvekl A, Tamm ER. Anterior eye development and ocular mesenchyme: New insights from mouse models and human diseases. BioEssays : news and reviews in molecular, cellular and developmental biology. 2004;26(4):374-386. doi:10.1002/bies.20009. Pupillary Membrane 3th month pupillary membrane forms between the lens epithelium and the corneal endothelium to replace the vascular tunic This transitory membrane contains components from the mesenchyme and branches from the major circle of the iris 6th month central vessels atrophy and become bloodless 8th month the central vessels fragmented and disappeared Reabsorption of the central pupillary membrane occurs (if not persistent pupillary membrane appears) Uvea Middle layer of the eye 3 regions: – Iris – Ciliary body – Choroid Vascular layer Iris Iris diameter: 12 mm Iris thickness: varies Collarette – Circular ridge approx. 1.5 mm from the pupillary margin – Thickest region of the iris – Site of attachment for the fetal pupillary membrane (embryologic development) – Divides the iris in Pupillary zone Ciliary zone (usually color defers between them) Fig. 10 Surface anatomy of the front of the iris. (Reprinted with permission from Bron AJ, Tripathi RC, Tripathi BJ. Wolff's Anatomy of the Eye and Orbit, 8th Edition. London: Chapman Hall Medical, 1997) Iris Circular structure located anterior to the lens Pupil: – Center aperture – Slightly nasal and inferior to the iris center – Pupil size regulates retinal illumination – Diameter 1 – 9 mm (light conditions) miotic myadriatic Iris Iris root: – Approx. 0.5mm thick – Thinnest part iris – Joins the iris to the ciliary body Iris divides anterior segment: – Anterior chamber – Posterior chamber (allows AH flow) Iris Histology Four layers: – Anterior border layer – Stroma and sphincter muscle – Anterior epithelium and dilator muscle – Posterior epithelium Iris layers Anterior Border Layer Thin condensation of the stroma Composition meshwork: – Fibroblasts (surface) – Pigmented Melanocytes (below, thickness varies throughout the iris) Accumulations form elevated freckle-like masses Absent in the iris crypts At the root form fingershaped iris processes attach to the trabecular meshwork Iris layers Iris Stroma and Sphincter Muscle Iris Stroma – composed Pigmented cells – Melanocytes – Clump cells (large, round, usually at the pupillary portion of the stroma) Non-pigmented cells – – – – Fibroblasts Lymphocytes Macrophages Mast cells Iris layers Iris Stroma and Sphincter Muscle Major circle of the iris – iris arteries – Radial course from the iris root to the pupil margin – Thick tunica adventitia – “thick-walled blood vessels” – Encircled by bundles of collagen fibrils for protection from kinking and compression Iris layers Iris Stroma and Sphincter Muscle Minor circle of the iris – Incomplete circular vessel – Located iris stroma inferior to the collarette – Not fenestrated and form part of the bloodaqueous barrier Iris layers Iris Stroma and Sphincter Muscle Sphincter muscle – Lies within the stroma – Composed Smooth muscle cells Join by tight junctions – Circular muscle (encircling the pupil) – Wide 0.75-1mm – Anchors firmly to the stroma – Contraction – pupil constriction – miosis – Innervation: parasympathetic system Iris Layers Anterior Epithelium and Dilator Muscle Anterior Iris Epithelium – Lies near to the stroma – Composed Myoepithelial cells Pigmented cuboidal epithelium (apical portion) join by tight junctions and desmosomes Smooth muscle processes (basal portion) Iris Layers Anterior Epithelium and Dilator Muscle Iris Layers Anterior Epithelium and Dilator Muscle Dilator muscle – 3 to 5 layers of muscle fibers extend into the stroma – Join by tight junctions – Present from the iris root to a midpoint of the sphincter in the stoma – Connective tissue band separates the sphincter and dilator muscles – Contraction Mydriasis – Innervation Sympathetic Iris Layers Anterior Epithelium and Dilator Muscle Iris Layers Posterior Epithelium Single layer Columnar heavily pigmented cells Joined by tight junctions and desmosomes Periphery loose pigment as continues into the ciliary body as nonpigmented epithelium Thin basement membrane covers the basal aspect Pupillary ruff (or frill) – Epithelial cells curl around the anterior epithelium at the pupillary margin – Encircles the pupil – Serrated appearance Anterior Iris Surface Crypts – Thicker branching trabeculae encircle depressions in the surface – Located both sides of collarette Fuch’s crypt Peripheral crypts (near the root) Light pigmented iris – Thin, radial collagenous columns of trabeculae Circular contraction folds – Pupillary dilatation Posterior Surface of the Iris Fairly smooth Near the pupil small circular furrows – Radial contraction furrows (of Schwalbe) Pupillary zone – Structural furrows (of Schwalbe) Deeper Through the ciliary zone and continue to the ciliary body Iris Color Determined by the number of melanin granules within the melanocytes and the area they occupy Reflection of the light also contributes Iris heavily pigmented appear have a velvety appearance, smooth and brown Lighter irises trabeculae are evident Nevus – Area of hyperpigmentation – Accumulation of melanocytes Ciliary Body Ring shaped structure (front) Width – – 5.9 mm nasal – 6.7 mm temporal Posterior area ends at the ora serrata (fairly flat) Anterior ciliary body contain numerous processes that extend into the posterior chamber Sagittal section has a triangular shape (base anteriorly) One corner of the base lies at the scleral spur Ciliary Body Divide in two parts: 1. Pars plana (orbicularis ciliaris) Flatter region Extends until the ora serrata (transition between ciliary body and choroid) Ora serrata: – serrated pattern – Dentate process or teeth – Oral bays (rounded portions between the teeth) Zonule fibers insert into the internal limiting membrane of the pars plana, some attaches on the valleys of the pars plicata Ciliary body is attached to the vitreous base Ciliary Body 2. Pars plicata (corona ciliaris) Wider part Contains ciliary processes – 70-80 – 2mm length, 0.5 mm width and 1mm height Valleys of Kuhnt (regions between ciliary processes) Ciliary Body Supraciliaris (Supraciliary lamina) Outermost layer Adjacent to the sclera Ribbon-like layers of loose connective tissue Contains pigmented melanocytes, fibroblasts and collagen bands Allow accumulation of fluid between the layers Trauma damage – detachment of the ciliary body Ciliary Body Ciliary Muscle Composed of smooth muscle fibers Longitudinal, radial and circular direction Longitudinal muscle fibers of Brücke – Lie adjacent to the supraciliaris and parallel to the sclera – Base is at the scleral spur and the apex is in the choroid Ciliary Body Ciliary Muscle Radial fibers – Form wider, shorter interdigitating Vs – originate at the scleral spur and insert into the connective tissue near the base of the ciliary processes – Transition layer from longitudinal to circular fibers Ciliary Body Ciliary Muscle Annular muscle of Müller’s – Circular bundles – Sphincter type action – Near the major circle of the iris Ciliary muscle innervation – Autonomic nervous system – Parasympathetic stimulation Muscle contraction Ciliary Body Ciliary Stroma High vascularized loose connective tissue Lies between the muscle and the epithelial layers Forms the core of each of the ciliary processes Anteriorly is continuous with the iris stroma Posteriorly continues as choroidal stroma In the stroma is the major arterial circle of the iris – Anterior to the circular muscle – Anastomosis of the long posterior ciliary arteries and the anterior ciliary arteries Ciliary Body Ciliary Epithelium Two layers of epithelium Cover ciliary body and line the posterior chamber as part of the vitreous chamber Two layers connected by intercellular junctions, desmosomes and tight junctions Gap junctions between the apical surfaces provide a communication between the layers and important in the formation of aqueous Both layers involved in aqueous secretion Ciliary Body Ciliary Epithelium Pigmented ciliary epithelium – Outer layer – Pigmented cuboidal epithelium – Joined by desmosomes and gap junctions – Anteriorly is continuous with the anterior iris epithelium – Posteriorly is continuous with the retinal pigment epithelium – Basement membrane attaches the pigmented epithelium to the stroma Ciliary Body Ciliary Epithelium Non-pigmented ciliary epithelium – Inner layer – Lining the posterior chamber – Composed of columnar cells in the pars plana and cuboidal cells in the pars plicata – Lateral walls of the cells contain interdigitations joined by desmosomes, gap junctions and zonula occludens Form one site of the blood aqueous barrier – Anteriorly continuous with the posterior iris epithelium – Posteriorly with the ora serrata and becomes the neural retina Ciliary Body Ciliary Epithelium Non-pigmented ciliary epithelium – Non-pigmented cells had greater number of mitochondria – Higher metabolic activity – Active secretion of aqueous humor components – Serve as a diffusion barrier between blood and aqueous Choroid Extends form the ora serrata to the optic nerve Located between the sclera and the retina Provide nutrients to the outer retinal layers Consist primarily of blood vessels (Hogan M, Alvarado J, Weddell J: Histology of the Human Eye—An Atlas and Textbook. Philadelphia: WB Saunders, 1971:326) Choroid Choroid Lamina Fuscha (Suprachoroid Lamina) Thin, pigmented, ribbonlike branching bands of connective tissue Traverse a potential space: suprachoroidal space or “perichoroidal”space between the sclera and the choroidal vessels Choroid Lamina Fuscha (Suprachoroid Lamina) Contains – Collagen bands and fibroblast (sclera) – Melanocytes (choroidal stroma) If the choroid separates from the sclera – Part of the suprachoroid will adhere to the sclera and part remain attached to the choroid Looseness of the tissue allows vascular swelling without detachment The suprachoroidal space carries the long posterior ciliary arteries and nerves Choroid Choroidal Stroma Pigmented, vascularized loose connective tissue layer Contains – Melanocytes, fibroblasts, macrophages, lymphocytes and mast cells Collagen fibrils arranged circularly around the vessels (branches of the short posterior ciliary arteries) Choroid Choroidal Stroma Two layers of vessels – Haller’s layer Outer layer Vessels with larger lumen – Sattler’s layer medium sized vessels Branches of the outer layer Continue branching to form capillary bed (choriocpillaris) Venules join to become the 4 vortex veins (no valves) Choroid Choroidal Stroma Choroidal vessels innervation – Autonomic nervous system – Sympathetic stimulation Vasoconstriction Decreased choroidal blood flow – Parasympathetic stimulation Nitrous oxide responsive vasodilatation Resulting in increased choroidal blood flow Choroid Choriocapillaris Single layer of anastomosing, fenestrated capillaries Most of the fenestrations face to the retina (facilitating movement of materials) Wide lumen – 3 – 4 times the lumen of an ordinary capillary – 2-3 red blood cells can pass through instead of 1 Choroid Choriocapillaris Occasional Pericytes (Rouget cells) are found around the capillary wall, have a contractile function Pericytes have the ability to alter local blood flow Choroid Choriocapillaris Choriocapillaris is densest in the macular area Fig. 16. Choroid at the macula: 1, internal limiting membrane of retina; 2, nerve fiber layer of retina; 3, ganglion cell layer of retina (multicell thickness); 4, inner plexiform layer; 5, bipolar cell layer; 6, outer plexiform layer; 7, nuclei of rods and cones; 8, outer limiting membrane; 9, cone (and rod) layer; 10, pigment epithelium of retina; 11, Bruch's membrane; 12, choriocapillaris (× 520, KEI 8982B). Choroid Bruch’s Membrane (Basal Lamina) Innermost layer Fuses with the retina Runs from the optic nerve to the ora serrata Multilaminated sheet containing a center layer of elastic fibers Choroid Bruch’s Membrane (Basal Lamina) Components (outer to inner) – Interrupted basement membrane of the choriocapillaris – Outer collagenous zone – Elastic layer – Inner collagenous zone – Basement membrane of the RPE cells Tight adhesion between choroid and the outer pigmented layer of the retina