Conjunctival Physiology Magrane Basic Science Course KATE MYRNA, DVM, MS, DACVO UNIVERSITY of GEORGIA Conjunctiva

Conjunctival Physiology Magrane Basic Science Course KATE MYRNA, DVM, MS, DACVO UNIVERSITY OF GEORGIA Conjunctiva

 Anterior surface of globe (bulbar conjunctiva), posterior surface of eyelids (palpebral conjunctiva), anterior and posterior surface of third eyelid

 Secretes mucus

 Site of Mucosal defense – immunocompetent cells

 Initiate and mediate inflammatory reactions

 Synthesize immunoglobulin

 Microvilli and enzyme activity allow phagocytosis of foreign particles Conjunctiva Anatomy

 Palpebral conjunctiva

 Mucocutaneous junction: zone behind the Meibomian gland openings where stratified keratinized squamous epithelium of the lid margin transitions to the stratified nonkeratinized squamous epithelium of the conjunctiva

 Tarsal conjunctiva

 Orbital/Bulbar conjunctiva – from the tarsal plate into the fornix

 Conjunctival Cul-de-sac or fornix

 Bulbar conjunctiva

 Scleral division: extends from fornix to limbus

 Conjunctiva, sclera and Tenon's capsule are firmly attached 3mm from the limbus

 Limbal division: 3mm wide ring at junction of conjunctiva and corneal epithelium Conjunctival Glands

 Serous

 Krause’s glands

 Deep in conjunctival fornix (40 superior, 6-8 inferior in humans)

 Wolfring’s glands

 2-5 in upper lid (along edge of tarsus)

 Fewer along lower edge of inferior tarsus

 Mucous

 Henle’s glands or crypts

 Epithelial invaginations within chorion, composed of goblet cells

 Along upper edge of superior tarsus

 Manz’s glands

 At limbus (reported in pigs, cattle and dogs; absent in human) Conjunctiva: Goblet Cells

 Mucus production per eye per day: 2-3mL in humans

 Mucins

 High molecular eight glycoproteins (2000-4000kDa) which form a gel

 Peroxidase

 Contribute to anti-infectious defense of ocular surface of tear film

 Hyaluronic acid?

 Some goblet cells synthesize it to stabilize the tear film Goblet Cell Response to Disease

 Proliferation

 KCS

 Chronic conjunctivitis

 Vitamin A deficiency Feline Conjunctiva

 Goblet cells in normal cats % GC/200 basal Epithelial cells Sebag et al 2016

 Anterior 3EL 48.8%

 Fornical 47%

 Palpebral 38.5%

 Bulbar 19.6%

 Posterior 12.6% Conjunctival Mucin Function

 Anchor aqueous layer of the tear film

 Tear film is organized into increasingly dense filaments as one approaches the cell layers

 Trap desquamated epithelial cells and acellular surface debris (organisms)

 Transported to medial canthus during blinking

 Immunological barrier

 Immobilize more than 30% of the secretory IgA contained in tear films Conjunctival Glycocalyx

 Glycoproteins and glycolipids that cover the microvilli and microplicae of the corneal/conjunctival epithelium

 Extends 300 nm from microvilli and microplicae

 Angular and branching and extends laterally between microvilli

 Filaments branch distally and associated with cell membrane

 Mucus layer attaches to glycocalyx

 Protects epithelium by causing shear forces of blinking to break up mucus layer away from cell surface

 Mucus attachment to glycocalyx allows aqueous layer to spread evenly Conjunctival Immunity

 Conjunctiva-associated lymphoid tissue (CALT)

 Uptakes and processes antigens

 Produces immunoglobulins and effector cells

 Has lymphoepithelium overlying B and T cell lymphoid population (FAE)

 Follicular associated epithelium (FAE)

 Contains membranous (M) cells

 M cells deliver antigen particles to lymphoid tissue below Conjunctival Diagnostics

 Impression cytology (Eordogh et al)

 Ideal technique with topical anesthesia and additional drying.

 SUPERIOR bulbar conjunctiva

 Biopore membrane device

Conjunctival monolayer

 Report as index of goblet cell/epithelial

 cell

 Normal 0.29-0.3 What is wrong? Conjunctivitis

 Chemosis

 Hyperemia

 Blepharospasm

 Cellular exudation Third eyelid: Nictitating Membrane

 Topographical distribution

 Originates in the anterior ventromedial orbit

 Triangular in shape; covered with conjunctiva

 “T-shaped” hyaline cartilage

 Function

 Protects the globe

 Secretion/distribution of tears

 Aid in removal of particulate matter Nictitans

 Movement – passive

 Orbital tone

 Orbital fat

 Hydration status

 Exception CATS

 Believed to have some smooth muscle and sympathetic innervation to third eyelid movement Nictitans: Cats

 Smooth muscle draws membrane to medial canthus

 Innervation: postganglionic adrenergic sympathetic nerve fibers with cell bodies in anterior cervical ganglion

 No spontaneous activity because smooth muscle lacks tight junctions that visceral smooth muscle has.

 Honestly the literature is confused on the subject…. Nictitans: Avian

 Translucent

 Movement under direct muscular control

 15/20 minute these muscles pull the nictitans over the cornea

 Contains a superficial tear gland Nictitans

 Gland of the 3rd Eyelid

 Encompasses base of cartilage

 Seromucous secretions in dog (serous in horses), exit through ducts open in posterior aspect of the third eyelid between lymphoid follicles

 Important contributor to basal tear production Eyelids Eyelids

 Functions

 Screening and sensing (cilia and vibrissae)

 Mechanical wiping action

 Secretions and spreading of glandular tissue

 Screening of light to allow sleep

 Most carnivores born with fused eyelids that open between 10 and 14 days Eyelid

Muscles: -Orbicularis oculi -Retractor anguli oculi -Levator anguli oculi -Muller’s muscle Eyelid

 Most movement-upper eyelid  Open-  levator palpebrae superioris (CNIII)

 Müller’s (sympathetic)  Closure-orbicularis oculi  Closure mediated by CN VII  Frontalis, retractor anguli medialis

 Malaris mm (lower eyelid depressor) Orbicularis oculi

 Major eyelid muscle  Concentric rings around palpebral opening  Fibers originate and terminate on medial palpebral ligament  Innervation CN VII  Function is eyelid closure  Specialized divisions:

 Horner’s muscle

 Branch that runs under lacrimal sac and inserts on medial orbital wall

 Negative pressure within lacrimal sac so as to pull tears into sac  Muscles of Riolan

 Travel along eyelid margin, surrounding the eyelash bulbs

 May rotate eyelashes toward eye and propel glandular contents during blink Levator palpebrae superioris and Muller’s muscle

 Levator palpebrae superioris

 Originates deep within orbit, dorsal to optic canal between origins of dorsal rectus and dorsal oblique

 Functions to elevate upper eyelid

 Innervated by CN III

 Muller’s muscle

 Portion of the levator palpebrae superioris that extends deeper into dermis

 Composed of smooth muscle fibers

 Innervated by sympathetic nervous system (carried by infratrochlear nerve, branch of nasociliary nerve which is branch of ophthalmic division of CNV)

 Functions to widen/elevate palpebral fissure Levator anguli oculi medialis and Frontalis

 Both are eyelid elevators

 Innervated by CN VII (palpebral branch)

 LAOM also known as corrugator supercilia

 Small muscle that arises caudodorsal to medial commissure

 Contraction raises the medial upper eyelid

 In horse gives rise to prominent lid notch Retractor anguli oculi lateralis

 Parallel and superficial to lateral palpebral ligament

 Innervated by zygomatic branch of CN VII

 Functions to draw lateral canthus posteriorly and laterally upon eyelid closure Pars palpebralis of the m. sphincter colli frofundus (Malaris muscle)

 Several straps of muscle originating near the ventral midline, coursing dorsally to insert on lower eyelid

 Ventral portion lies deep to the platysma

 Dorsal portion is subcutaneous and close to eyelid skin

 Innervated by buccal branches of CN VII

 Functions to depress lower eyelid Eyelid Movement

 Most species have Superior lid most mobile

 Innervation to levator palpebrae superioris m follows Hering’s law

 Synergistic muscles receive simultaneous and equal innervation

 Motor neurons for levator m. arise from single unpaired central caudal nucleus of the oculomotor complex, and a single motor neuron may innervate bilaterally

 Hence, any supranuclear input into motor neuron influences BOTH levator muscles

 Clinical significance: when the levator on one side is weak, the lid on opposite side may be retracted in an unconscious attempt to elevate the ptotic lid. Eyelids

Length, orbit size, medial and lateral canthal ligaments all determine palpebral fissure

 Brachycephalic is shallow orbit and large eyelid opening and tight medial canthal ligament = ?

 Spaniel is normal globe and orbit with long lids and a strong lateral canthal ligament = ?

 Shar pei = ???? Eyelids: “normal” length?

 Average length when stretched by calipers = 33mm

 If lower lid doesn’t contact globe length >39mm Eyelid Sensory Nerves : Dog

 Sensory: CN V (Trigeminal)  Maxillary Division Zygomaticotemporal nerve: lateral dorsal lid Zygomaticofacial nerve: lateral ventral lid  Ophthalmic Division Frontal (Supraorbital) nerve: middle portion of upper lid. Infratrochlear nerve: medial dorsal and ventral lid. Eyelid Sensory Horse

 Red: zygomaticofacial nerve (branch of maxillary division of trigeminal)

 Yellow: zygomaticotemporal nerve (branch of maxillary division of trigeminal)

 Blue: Frontal or supraorbital nerve (branch of ophthalmic division of trigeminal)

 Green: Infratrochlear nerve (branch of ophthalmic division of trigeminal) Eyelid

 Composed of skin, palpebral conjunctiva, muscle, glandular tissue (Meibomian glands)

 Ducts of meibomian glands on lid margin Eyelid Glands

 Glands of Zeis and Moll

 Anterior lamella of eyelid

 Associated with eyelash cilia

 Secrete contents around lash follicle shaft

 Zeis

 Modified sebaceous glands

 Surround base of hair follicles

 Moll

 Eccrine, or modified sweat glands

 Located just deep to the hair follicles  Meibomian/Tarsal glands

 Holocrine, sebaceous glands not associated with cilia

 Produce lipid layer of tear film

 Secretion under hormonal and neural control Normal Tarsal Gland of the Eyelid

Histopathologic features of canine distichiasis, Volume: 15, Issue: 2, Pages: 92-97, First published: 29 September 2011, DOI: (10.1111/j.1463-5224.2011.00946.x) Distichia of the Tarsal Gland of the Eyelid

Histopathologic features of canine distichiasis, Volume: 15, Issue: 2, Pages: 92-97, First published: 29 September 2011, DOI: (10.1111/j.1463-5224.2011.00946.x) Eyelid Skin

 Epidermis

 Strata corneum & granular, spinous and basal layers

 Dermis

 Dense, irregular connective tissue

 Most species devoid of far (exception Shar Pei)

 Hair follicles extend deep into dermis

 Palpebral margin

 Transition from keratinized/stratified epithelium to non-keratinized/stratified squamous epithelium

 Eyelashes/Cilia located on eyelid leading edge

 Normal turnover times 3-5 months, regrow in 1 months Cilia

SPECIES LOCATION ON EYELIDS Human Upper and lower Canine Upper Porcine Upper Equine Upper and few on lower; vibrissae Ruminant Upper and lower Feline None per se (normal hair appears as cilia) Avian Some species have filoplumes: rudimentary feathers without barbs Blinking

 Spontaneous blinking

 Most common (15/min humans)

 Lateral to medial (part of lacrimal pump mechanism)

 Clinical significance? TFBUT? Blinks/min % bilateral blinks

Dog: 3-5/min 85%

Cat: 1-5/min 70%

Horse: 5-25/min 30%

Pig: 10/min 90% Pathology of the Eyelid

 Ankyloblepharon

 Delayed of complete failure of the lids to open

 Ususally bilateral

 Ophthalmia neonatorum is a differential (swollen with discharge)