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Physiology of the Tear Film and Adnexa

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Physiology of the Tear Film and Adnexa Special Thanks Physiology of the Tear Film and Acknowledgements and Adnexa (content and photos) 1. Dr. Mike Davidson 2016 William Magrane Basic Science Course 2. Contributions by in Veterinary & Comparative Ophthalmology ACVO/ECVO colleagues Elizabeth A. Giuliano, DVM, MS 3. Current/former members Diplomate, ACVO of the MU-CVM Comparative Ophthalmology service Today’s Objectives Today’s Objectives 3) Summary charts – helpful for boards 1) Discuss the “lacrimal functional unit” with emphasis on innervation, normal 4) “The brain can only absorb what the #%$@ physiologic function, and a review of can withstand” pathologic mechanisms in dry eye Clinical cases – our passion What does this lecturer “bring to the table”? 2) Review mammalian eyelid anatomy CALT and PDT Encourage your creative juices “Lacrimal Functional Unit (L.F.U.)” A complex functional unit which modulates the homeostasis of the ocular surface Lacrimal gland Tear film Ocular surface epith. Cornea, conjunctiva, meibomian glands Eyelids Interconnecting sensory and motor nerves 1 “Lacrimal Functional Unit (L.F.U.)” Control of Tear Secretion – New Concepts Traditional Normal tears: the result of intrinsic lacrimal gland activity; neural participation in reflex tears only New concept: tears under constant neural regulation On-going homeostatic regulation of the ocular surface Suggests a relatively constant level of neural signals that precisely meter tear production; may mediate lipid & mucin secretion also Stern, Gao, Siemasko et al Experimental Eye Research, 2004 Control of Tear Secretion – New Concepts Lacrimal Gland Innervation: Afferent Pathway of Trigeminal Ganglion-Mediated Reflex Control mechanism includes Irritation of cornea/conjunctiva stimulates afferent afferent nerves from the cornea nerves: Impulses are carried along lacrimal nerve & other ocular surface tissues the ophthalmic division of the trigeminal nerve central nervous system relay sensory nuclei in trigeminal ganglion (TG) nuclei efferent nerves Lacrimal nerve - smallest branch of the ophthalmic n. comprise the autonomic innervation to secretory tissues Courses laterally within the orbital cavity above and along the upper border of the lateral rectus muscle whose products contribute to Relevance? the tear film Lacrimal Gland Innervation: Lacrimal Gland Innervation: Afferent Pathway of Trigeminal Ganglion-Mediated Reflex Afferent Pathway of Trigeminal Ganglion- Trigeminal ganglion is Mediated Reflex Cornea connected to lacrimal conjunctiva Lacrimal nerve Ophthalmic nerve stimulus nucleus of facial nerve in Trigeminal pons by internuncial ganglion neurons Lacrimal gland Maxillary nerve Impulses are directed, by Mandibular nerve Pons way of the trigeminal ganglion, to the lacrimal nucleus Lacrimal nucleus of the facial nerve in the pons Slide courtesy of Dr. Ota 2 Lacrimal Gland Lacrimal Gland – Innervation Additional Sensory Innervation Recommend Gia Klauss’s chapter on “non-hypotensive autonomic agents in The afferent innervation of the lacrimal gland is also veterinary ophthalmology” VCNA, Ocular therapeutics, 2004 provided by the ipsilateral superior vagal ganglion (SVG) and superior glossopharyngeal ganglion Autonomic innervation - sympathetic: (SGG) The sympathetic postganglionic fibers arise from the There may be SVG and SGG-mediated reflexes in cranial cervical sympathetic ganglion which is the addition to the TG-mediated reflex uppermost ganglion of the sympathetic trunk and travel in S.B Cheng et al. Three novel neural pathways to the the plexus of nerves around the internal carotid artery lacrimal glands of the cat. Brain Research 873 (2000) They join the maxillary nerve, the zygomatic nerve, the In humans, there is a connection between zygomaticotemporal nerve and finally the lacrimal nerve hypothalamus and lacrimal nucleus (emotional (a branch of the ophthalmic nerve) tears), and between olfactory system and lacrimal nucleus (“wasabe tears”) Slide courtesy of Dr. Ota Lacrimal Gland – Innervation Recommend Gia Klauss’s chapter on “non-hypotensive autonomic agents in Sympathetic innervation veterinary ophthalmology” VCNA, Ocular therapeutics, 2004 Autonomic innervation - sympathetic: Lacrimal gland Lacrimal nerve Post-ganglion fibers join the maxillary nerve, the zygomatic nerve, vascular smooth Zygomatic Ophthalmic nerve the zygomaticotemporal nerve and finally the lacrimal nerve (a muscle branch of the ophthalmic nerve) nerve Acinar cells, Maxillary nerve T1 Distributed to interstitium surrounding acini and to vascular ductules and tubules smooth muscle fibers of glands Plexus of nerves around the internal Sympathetic nerves contain norepinephrine and neuropeptide Y carotid artery (NPY) Sympathetic stimulation increases tear secretion by affecting Cranial cervical ↑ protein secretion sympathetic ganglion vascular supply to lacrimal gland as well as activating a G ↑ blood flow protein pathway In some species, the sympathetic nervous system may influence tear secretion, not only by modulating blood flow to the gland and its distribution within it, but also by direct effects on the secretory acini. Lacrimal Gland – Innervation Lacrimal Gland – Innervation Autonomic innervation - Autonomic innervation - parasympathetic parasympathetic The efferent postganglionic parasympathetic impulses Parasympathetic secromotor are then transmitted via sphenopalatine nerve to the nerve supply to lacrimal gland zygomatic nerve (a branch of the maxillary division of is derived from the lacrimal the trigeminal nerve). They then pass into zygomatic nucleus of the facial nerve temporal nerve which reaches the lacrimal gland The pre-ganglionic fibers reach The zygomatic temporal nerve also gives off a recurrent branch the pterygopalatine to the lacrimal nerve, from which the efferent fibers terminate in the lacrimal gland (sphenopalatine) ganglion via the great petrosal nerve and vidian nerves as they pass through the pterygoid canal 3 Lacrimal Gland – Innervation Lacrimal Gland – Innervation Autonomic innervation – parasympathetic Autonomic innervation – parasympathetic Postganglionic parasympathetic fibers innervate: Lacrimal gland secretion inhibited by Leu-Enkephaline (L-Enk) Acinar cells, duct cells, and blood vessels A neuropeptide that interacts with inhibitory G proteins Interferes with activation adenylate cyclase by G stimulatory Exert principal neural control of electrolyte, water, and proteins protein secretion Postganglionic parasympathetic fibers also innervate the Stimulatory effect mediated via acetylcholine and nasal glands via the caudal nasal nerve (from the vasoactive intestinal peptide (VIP) maxillary nerve of the trigeminal nerve) Increase in tear secretion through a G protein pathway and perhaps a calcium/calmodulin pathway Lacrimal Gland – Innervation Parasympathetic innervation Autonomic innervation – parasympathetic Lacrimal nerve Ophthalmic nerve Postganglionic Zygomatic Trigeminal Lacrimal gland nerve ganglion parasympathetic fibers acinar cells, tubules Zygomatico Maxillary nerve ductules and temporal also innervate the nasal vascular wall nerve Mandibular nerve glands via the caudal Pons nasal nerve (from the Electrolyte and maxillary nerve of the water secretion Pterygoid canal trigeminal nerve) Sphenopalatine Vidian n. Greater petrosal n. nerve Lacrimal nucleus Pterygopalatine CN VII (Sphenopalatine) ganglion Post-ganglionic parasympathetic fibers Pre-ganglionic parasympathetic fibers Slide courtesy of Dr. Ota Additional References Parasympathetic innervation Lacrimal Gland Innervation Ding C, Walcott B, Keyser KT. Sympathetic neural control of the More than one parasympathetic ganglion is mouse lacrimal gland. Invest Ophthalmol vis Sci. 2003; 44: 1513- involved in the neural regulation of lacrimal gland 1520 secretion. Cheng S, Kuchiiwa S, Kuchiiwa T et al. Three novel pathways to the Ciliary ganglion (CG) lacrimal glands of the cat: an investigation with cholera toxin B Otic ganglion (OG) subunit as a retrograde tracer. Brain Res. 2003; 873:160-164 J. Anat. 199 (1996), Brain Res 873 (2000) Powell CC, Martin CL. Distribution of cholinergic and adrenergic nerve fibers in the lacrimal glands of dogs. Am JVet Res 1989; 50: Some anatomical studies suggest that small 2084-2088 neurons mediate the vasodilation of the lacrimal Text Books gland, while the large neurons mediate the Milder B. The lacrimal system lacrimal secretion Snell RS, Lemp MA. Clinical Anatomy of the eye Kaufman PL, Alm A. Adler’s Physiology of the eye Brain Res 873(2000), Brain Res 522 (1990) Krachmer JH, Mannis MJ, Holland EJ. Cornea 4 “Veterinary Neurology” by Oliver, Hoerlein, and Mayhew “Lacrimal Functional Unit (L.F.U.)” Tear Film – Anatomy & Physiology the “traditional” teaching Normal tears essential: Lipid Most superficial layer 1. To prevent surface infection Stabilize & prevent evaporation of 2. Provide a pure optical surface for light refraction aqueous layer Produced by the meibomian glands 3. Maintenance of surface “homeostatic” environment Aqueous Intermediate layer Provides corneal nutrition; removes waste products Concept of L.F.U. – first introduced by Stern Produced by orbital gland AND et al Cornea, 1998 gland of the 3rd eyelid Describe the relationship between ocular surface Mucus and the lacrimal glands in normal tear secretion Interface of tear film with and during inflammation hydrophobic cornea Secretory IgA Composed of tear film, ocular surface epithelium, Produced by conjunctival goblet eyelids, interconnecting sensory and motor nerves cells Tear Film – Functional Anatomy Continually
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