Module 2 Flashcards
Gastrulation and neurulation
Gastrulation (day 10); epiblasts migrate towards primitive streak and invaginate –> mesoderm. Ectoderm, mesoderm, endoderm.
Neurulation; the columnar surface ectoderm proliferates, forms elevations, neural folds–> elevate and approach each other and will form neural tube. Mesenchymal cells forming neural crest migrate out, spread throughout the embryo giving rise to connective tissue for the eye.
In other parts of the body mesenchyme is predominantly mesoderm in origin, not from neural crest.
The exterior is covered with surface ectoderm, then neural segmentation occurs forming forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon. Forebrain–>optic vesicle from neuroectoderm, midbrain–> connective tissues from neural crest
Optic vesicle and optic cup
By day 13 - optic sulci; paired evaginations of forebrain, then transformed to optic vesicle simultaneously with neural tube closure (day 15, also when aqueous humour starts to be produced).
Optic vesicle enlarges, approaches surface ectoderm. Optic vesicle significant in determining palpebral fissure and other orbital structures. Bulge seen by day 17. Optic vesicle and stalk invaginate. Surface ectoderm thickens–> lens placode –> invaginates within neural ectoderm –> double layer of neuroectoderm in the optic cup –> inferior to superior progression; note optic fissure, day 25 hyaloid artery develops in optic fissure and supplies lens. Fissure meets and closes (failure here results in colobomas as 6 o’clock position) –> IOP can be established
Lens formation
Adhesion of lens placode and optic vesicle assure alignment with retina. Lens placode invaginates - hollow sphere; lens vesicle, which then detaches (day 25). (Failures = anterior lenticonus, anterior capsular cataracts, anterior segment dysgenesis).
Vesicle then lined with a monolayer of cuboidal cells with basal lamina - lens capsule.
Primary lens fibres - stim by retina, form embryonic lens nucleus.
Cortex; minimal at birth, continues to develop, anterior cuboidal epithelial cells, differentiate into secondary fibres at equator and meet at Y sutures.
Zonule fibres (tertiary vitreous) - ?origin, ?ciliary epithelium or endothelium of posterior tunica vasculosis lentis.
Lens abnormalities: spherophakia, coloboma, flattened equator
Vascular development
Mesoderm–> hyaloid vasculature. Hyaloid artery = termination of ophthalmic artery. Hyaloid vessels enclosed in ON as fissure closed.
Anterior and posterior tunica vasculosis lentis; hyaloid artery branches around posterior lens and continues anteriorly, anastomoses with the vessels in the pupillary membrane (mesenchyme and vessels overlying anterior lens capsule) (at max day 45).
Hyaloid regresses posterior to anterior as lens now nourished by aqueous although may still support lens up to 3 days postnatally.
Mittendorf’s dot fibrosis on posterior lens capsule, incomplete regression.
Choroid develops on outer surface of optic cup –> ciliary arteries –> retinal vessels. Glial cells sheathing hyaloid may persist at ONH; Bergmeister’s papilla.
Cornea and anterior chamber
Surface ectoderm–> thick matrix; primary stroma
Mesenchymal neural crest –> endothelium and stroma, anterior iris stroma, ciliary muscle, iridocorneal angle structures. Also sheet of mesenchymal tissue, some of which forms pupillary membrane, rest eventually becomes anterior chamber
Endothelium day 30-35 –> secretes Descemet’s membrane
Cornea - transparent by end of gestation
Lids open day 14, corneal thickness increases initially for 4 weeks, then decreases over 6 months.
Development of iris, ciliary body and iridocorneal angle
Neuroectoderm layers cover ciliary muscle and posterior surface of pupillary membrane, then fuse with open centre to become iris and pupil.
Pupillary membrane starts to degenerate day 45 and continues to degenerate until day 14 postnatally.
Two layers of neuroectoderm- non-pigmented (inner) pigmented (outer)
Iris and ciliary body epithelium - anterior rim of cup, retina - posterior cup
Retina and ON development
From forebrain. Ectoderm from outer optic cup –> RPE.
Ectoderm of inner optic cup –> neurosensory retina.
Two layers of epithelia are separated by a space, the cavity of the optic cup, which has decreased during invagination, disease occurs in this space, separating RPE from sensory retina.
Neuroblastic layer –> inner and outer neuroblastic layer separated by a fibre layer. Outer neuroblastic layer –> cones and rods externally and horizontal cells (thus next to choroid and own blood supply). Inner neuroblastic layer –> ganglion cells, amacrine cells, bipolar cells and muller’s cells.
ERG signals reach adult amplitude at 5-8weeks.
Axons from ganglion cells –>towards optic stalk–>nerve fibre layer; innermost layer of the retina. Converge forming bundles–> ON. Synapse at lateral geniculate nucleus.
Sclera, choroid, tapetum
Neural crest–> inner vascular layer (–> choroid) & outer fibrous layer (–> sclera, which is continuous with dura mata of ON).
Tapetum continues to develop 4 months after birth, initially mottled blue appearance is replaced by blue/green to yellow/orange sheet.
Subalbinotic animals have a higher incidence of posterior segment colobomas with reduced RPE pigmentation being the marker e.g. CEA
Vitreous
Primary: mesodermal tissue - hyaloid vasculature–> tunica vasculosis lentis, nourishes lens until day 45. Compressed by secondary vitreous, atrophied by 2-4 weeks postnatally.
Secondary: adult vitreous. Ectoderm and neuroectoderm, forms fibrils continuous with muller cells. Attached at pars plana, ora ciliaris retina, hyaloidiocapsular ligament. Remnants: mittendorf’s dot on posterior capsule or a clear central canal cloquet’s canal.
Tertiary: len zonules - secreted by ciliary epithelium?
Eyelids and TEL
Lower and TEL from maxillary processes
Upper from paraxial mesoderm
Upper and lower fused until 10-14 days postnatally
Surface ectoderm: conjunctiva, cilia, glands, lid epidermis
Neural crest: tarsus, lid dermis
Mesoderm: lid muscles
Nasolacrimal system
Nasolacrimal groove - lateral nasal fold from maxillary processes
Solid tube of ectodermal cells form and gets buried in maxillary process
Two buds form from proximal end towards medial canthus, forming inferior and superior lacrimal puncta
Distal end enters ventral nasal meatus
Chord becomes duct by canalisation
Imperforate puncta can occur - usually lower one
EOM
Neural crest –> secondary mesenchyme in orbit –> EOM
Postnatal development
Retina: inner segments first week, outer segments by second week. Mature by 6 weeks.
Corneal oedema - impossible to examine fundus <2weeks, around this time tapetal and non-tapetal fundus cannot be differentiated on exam. ONH is small and fundus is dark and grey, vessels large
3-4 weeks tapetal fundus defined as paler area –> lilac/blue
7-8 weeks tapetal fundus granular in appearance
4 month - adult tapetal structure and colour
Cornea - intro
1/6 outer tunic
Refracts and transmits light to retina, anterior surface contributes 48D of plus power towards convergence on the retina.
Oxygen derived from tear film, nutrition from aqueous humour.
Protects eye: chemical barrier through tight junctions superficially, subepithelial nerve plexus, fine nerve endings; do not impact clarity.
Immunoglobulins and anti-microbials provided in the tear film, blinking and epithelial desquamation, migrating Langerhans cells and macrophages from limbus
Tear film: 7um thick. Lipids - meibomian glands, aqueous - lacrimal glands, mucin - goblet cells.
Epithelium
5-7 layers. Stratified, squamous, non-keratinised and non-secretory. 50-60um.
Outermost layer most differentiated, tight junctions, zona occludens, obliterate intercellular space. Anterior plasma membrane - microvilli
Superficial layer 3-4 layers flattened, nucleated, squames
Intermediate layer 2-3 layers interdigitating, wing and polygonal cells.
Basal columnar cells are adhered to 50nm thick basement membrane.
Basement membrane 40-60nm thick
Epithelial cell adhesions
Superficial - tight junctions (barrier function) and desmosomes. Tight junctions/zona occludens completely encircle cell. Anastomosis lipid bilayer of adjoining membranes
Wing cells - beneath superficial cells. Desmosomes and gap junctions. Intercellular communication
Basal cells - desmosomes and gap junctions. Hemidesmosomes attach to basement membrane
Base membrane - specialised extracellular matrix, has a lamina lucida and lamina densa, laminin, collagen IV and proteoglycans Roles include: a) maintaining structure, b) anchorage, c) selective barrier d) filtration and temporary storage, e) involved in biological processes including embryonic development
Stroma
500um thick. 90% of corneal thickness. Lamellae - flattened bundles of collagen fibrils. Highly organised. Stromal fibroblasts (keratocytes) reside between lamellae and secrete the lamellar stroma. Proteoglycan molecules cross-link the lamellae. Collagen I mostly, some II, V and VI.
Keratocytes perform constant remodelling as maintenance. Proteases enable this function. Over production by fibroblasts, bacteria and inflammatory cells results in melting ulcers.
Primates - Bowman’s layer - acellular layer in stroma
Stromal basement membrane = Descemet’s membrane and is secrete by the endothelium
Endothelium
Low cuboidal, single-layered endothelium. No adhesive junctions with Descemet’s membrane. Interdigitation with other fellow cells, tight junctions and gap junctions (intercellular communication) with occasional desmosomes. Tight junctions only laterally so barrier is leaky.
Mitochondria +++, smooth and rough endoplastic reticulum, golgi apparatus.
Na+K- ATPase pump to maintain corneal hydration.
Does not self renew, enlarges to fill defects.
Corneal innervation
CN V –> myelinated nerve leashes –> anterior stroma below Bowman’s layer.
Nerve sheath lost during penetration of basement membrane
Naked nerve endings send terminus up between cell layer, terminating at outer most squames.
300-400 more nerve endings cf. epidermis
Corneal nutrition
Tear film - oxygen
Limbal vessels and aqueous humour - glucose and amino acids