signature symptoms are xerostomia and xerophthalmia, although due to the mucosal nature of this inßammatory disease, periodic ßare-ups can occur in the lungs, gut, and vagina. Diagnosis of this disease is commonly made by identifying dryness of the mouth and eyes and the presence of circulating (serum) antibodies [anti-ro, antila (SSA, SSB)]. In some cases a labial biopsy of a minor salivary gland is taken to look for lymphocytic foci.

13.2The Lacrimal Functional Unit (LFU)

The ophthalmic pathology seen in SjšgrenÕs syndrome surrounds an immune-based inßammatory disruption of the lacrimal functional unit (LFU). The LFU is composed of the ocular surface (cornea, conjunctiva, conjunctival blood vessels), eyelids, the lacrimal glands (main and accessory [Wolfring and Krauss]), and the interconnecting innervation (V, VII) [1]. This tear-secreting reßex is also modulated with input from hormonal and immune factors. The role of the LFU is to secrete a tear Þlm of speciÞc composition in order to maintain a trophic (i.e., homeostatic) environment around the epithelial cells of the ocular surface.

13.3The General Role of the LFU in Normal and Pathological Situation

The important purpose of the ocular surface is to preserve corneal clarity and vision. The main and accessory lacrimal glands, the corneal limbus, and the meibomian glands provide a vital supportive function to protect the sensitive epithelial surfaces of the conjunctival and corneal tissues from injury, which could result in loss of vision. The main function of the LFU is secretion of tear constituents that help to sustain a stable, defensive, and supportive tear layer that is essential for the optics of the eye to function at optimal levels [1]. Bioelectric energy emanating from ocular surface sensory nerves supplies continuous input

into CNS pathways, which connect changes in the ocular surface milieu with tear secretory activity by these specialized support tissues.

13.4Innervation of the Lacrimal Functional Unit

Normal tears are secreted when the highly innervated corneal nerves are subconsciously stimulated. This can occur from a variety of stresses; however, environmentally induced Òdry spotÓ formation is thought to be a normal stimulus. Through evolution the cornea has become the most densely sensory nerve innervated epithelial surface in the body. Myelinated and unmyelinated nerves end in the cornea, limbus, and conjunctiva epithelium and are associated with conduction of pain. The neural receptors in the cornea are free nerve endings which terminate in the wing cell layer of the corneal epithelium. These nerve ending are protected from direct irritation by zonula occludens in and tear mucin gel adherent to the apical corneal epithelial cells [2, 3]. Afferent nerve trafÞc through the ophthalmic branch of the trigeminal nerve (V) enters the central nervous system in the area of the pons (midbrain) and the para-spinal sympathetic tract. These signals are integrated with cortical and other inputs and trigger efferent secretomotor impulses to stimulate secretion of the components of the tear Þlm.

13.5Efferent Structures

13.5.1 Lacrimal Glands

Tear secretion by the lacrimal gland occurs in response to neural stimulation [4]. The acni, ducts, and blood vessels of the lacrimal gland are innervated by parasympathetic, sympathetic, and sensory nerves. Signaling pathways are initiated by parasympathetic cholinergic nerves releasing acetylcholine, which then binds to M3 acetylcholine receptors on the basolateral cell membrane of secretory epithelia [5, 6], and vasoactive intestinal peptide (VIP) binds to