Читать книгу Essentials of Veterinary Ophthalmology - Kirk N. Gelatt - Страница 72

Both the optical and normal functions of the cornea depend on the integrity of the lacrimal system. The PTF maintains an optically uniform corneal surface by smoothing out minor irregularities, removing foreign matter from the cornea and conjunctiva, lubricating the conjunctiva and cornea, providing nutrients to the avascular cornea, and controlling the local bacterial flora. The PTF also undergoes constant evaporation and formation of transient “dry spots.” Hence, the rate of tear evaporation appears to be directly related to the rate of blinking, since the rate of blinking is faster than the development of these dry spots. Actual tear flow rates are difficult to measure in most species; however, in the horse, the tear flow rate has been estimated to be 34 μl/min with a tear volume of 234 μl, which indicates a turnover of the tear volume in approximately 7 minutes. By comparison, tear turnover and tear evaporation rates in humans are ~1 ± 0.4 and 0.14 ± 0.07 μl/min, respectively.

In all species studied, the PTF can be loosely divided into three layers that intermix (Figure 2.1). The outer oily layer (~0.1 μm) is very thin and forms a reversible, noncollapsible, multilayer film with the primary purpose of stabilizing the air–tear interface (and preventing evaporation). The primary constituent of this lipid layer is the meibomian gland secretion (MGS), or meibum, a composite lipid‐rich mixture. Up to 22 wt% comprises nonlipid components (proteins, salts, and polysaccharides). The main lipid classes found in canine MGS are very long chain cholesteryl esters, wax esters, (O‐acyl)‐omega‐hydroxy fatty acids (OAHFAs), and cholesteryl esters of OAHFAs. Dogs have a relatively larger proportion of OAHFAs than humans, which could be related to a higher tear film stability and lower blink rate in dogs versus humans. The same types of molecules are found in the MGS of cattle, rodents, and marsupials. This outer lipid layer prevents not only evaporation of the underlying layers but also the overflow of tear film onto the eyelids, spreads over the aqueous subphase, imparts stability to the tear film, thickens the aqueous subphase, provides a smooth optical surface for the cornea, constitutes a barrier against foreign particles, provides some antimicrobial activity, and seals the lid margins during prolonged closure. Additionally, it prevents maceration of the lid skin by the tears.

Figure 2.1 The tear film is a complex multilayered fluid phase. This figure represents the classic three‐layered model, composed of a mucin‐gel layer adjacent to the epithelial surface, an aqueous layer containing mucin and other soluble proteins, and a thin lipid film on the outermost surface.

The middle aqueous layer (∼7 μm) is the thickest (>60% of the total tear film thickness) and performs the primary nutritional functions of the tear film. This layer is composed of ~98% water and ~2% solids, comprising predominantly proteins. The aqueous layer contains inorganic salts, glucose, urea, proteins, glycoproteins, and soluble mucins. The lacrimal gland, gland of the NM, harderian gland, and accessory lacrimal glands in the conjunctiva all contribute to its formation. Destruction or excision of the canine lacrimal gland or NM gland results in a variable reduction in aqueous tear production, and indicates that approximately two‐thirds of the aqueous tear production is produced by the lacrimal gland, approximately one‐third by the gland of the third eyelid, and a very minor amount by the accessory lacrimal glands in the conjunctiva. The aqueous portion is evaluated clinically primarily through use of the Schirmer tear test (STT) I; the phenol red thread test can be used in very small animals.

The deep, or mucin, layer (∼1 μm) is composed of tear mucins produced by the apocrine conjunctival goblet cells, as well as an underlying glycocalyx that is associated with the corneal and conjunctival microvilli. The distribution of goblet cells varies among species, but the fornix is rich in goblet cells in dogs, cats, and horses, whereas the highest density in chinchillas and guinea pigs is in the palpebral conjunctiva. All species have lower concentrations of goblet cells in the bulbar conjunctiva. Mucin is produced by goblet cells in response to mechanical, immune, histamine, antigenic, or (direct or indirect) neural stimulation. The glycocalyx comprises polysaccharides that are produced by the stratified squamous epithelial cells of the cornea and conjunctiva and project from the surface microvilli of those cells. Mucins play a critical role in lubricating the corneal surface, thus making its hydrophobic surface more hydrophilic (to permit spreading), and in stabilizing the PTF. The mucin layer as well as the integrity of the outermost layer of corneal epithelium is necessary for retention of the tear film on the cornea.

Tears are a clear and slightly alkaline solution, with a mean pH of 8.3, 8.1, and 7.8 in cattle, dogs, and horses, respectively. In humans, horses, cattle, and rabbits, tear electrolyte concentration is similar to that in plasma, except for potassium, which is three to six times more abundant in tears, thus indicating an active transport mechanism. Tear film osmolarity/osmolality is influenced by the rate of tear secretion, evaporation, and composition. It is similar in cats (329 mOsm/l), dogs (356 mOsm/l), and rabbits (376 mmol/kg), whereas humans (283 mmol/kg) and horses (284 mmol/kg) have a lower osmolarity.

The PTF contains both nonspecific and specific antimicrobial substances. Nonspecific substances include lysozyme, lactoferrin, α‐lysine, and complement. Specific antimicrobial substances include secretory immunoglobulins A, G, and M. Toll‐like receptors that play a role in the defense against many types of microbial infections are expressed by the corneal and conjunctival epithelial cells in humans and horses. Protein concentrations in canine tears average 0.35 g/dl, with 93% globulin, 4% albumin, and 3% lysozyme, which is a ubiquitous antibacterial enzyme that hydrolyzes bacterial cell walls. Lysozyme is produced by the conjunctival goblet cells and has antibacterial and antifungal properties; its concentration increases with conjunctivitis. Relative to humans and nonhuman primates, domestic animals have very low amounts of lysozyme (e.g., the horse has one‐half to one‐fourth that of human tears) and the cat has none. Lysozyme activity has not been detected in cattle, but it has been detected in sheep and goats. Lactoferrin has been identified in the PTF of humans, dogs, cats, cattle, and other mammals, and reversibly binds the iron that is available for bacterial metabolism and growth. Immunoglobulin A (IgA) contributes to ocular defense by coating bacterial and viral microorganisms, leading to agglutination, neutralization, and lysis. IgA is present in greater concentrations in the PTF than immunoglobulins G and M. Cat tears have a 6.6 mg/ml total protein concentration with 9.7% IgA.

The lacrimal nerve, a branch of the trigeminal nerve, is primarily sensory but also provides the lacrimal gland with its parasympathetic (release acetylcholine and vasoactive intestinal peptide neurotransmitters) and sympathetic (release norepinephrine and neuropeptide Y neurotransmitters) innervation. Both adrenergic and cholinergic distribution patterns around the acini and blood vessels of the canine lacrimal gland are similar; however, the cholinergic fibers appear to be greater in number than the adrenergic fibers.

Lacrimation is stimulated by painful irritants, eye diseases, mechanical or olfactory stimuli of the nasal mucous membranes, and sinus diseases. Tear production as assessed with the external ocular surfaces anesthetized and the lower conjunctival fornix dried by Dacron swabs (STT II) measures ~50% of that measured without manipulation (STT II) in the cat and dog. Larger dogs also have greater wetting per minute than smaller dogs as measured with STT I. Additionally, canine neonates have lower tear production than adults. Clinical estimation of the rate of evaporation (and, indirectly, of the mucus component of the PTF) is performed through determining the time (in seconds) for the tear film using topical fluorescein to break up (development of “dry spots”).

The nasolacrimal drainage system eliminates used tear film and any excessive tears. The PTF accumulates along the palpebral margin of each eyelid and is forced by blinking to move medially into the upper and primarily the lower lacrimal puncta. When the tears are in the lacrimal pool and the facial muscles relax, the tears flow into the lacrimal canaliculi by capillary action. Normal breathing movements also facilitate this flow into the canaliculi. Reflex blinking of the eyelids closes the lacrimal sac, which acts as a passive pump. Pseudoperistaltic motion of the nasolacrimal duct allows movement of the tears into the nasal cavity. Autoregulation of the lacrimal system with receptors in the excretory portion has been suggested in studies of human tear flow. Evaluation of canalicular function in humans suggests that destruction of either canaliculus alone does not affect excretion of tears; in domestic animals, the lower canaliculus is considered to be the primary site for tear drainage.