Concomitant with the blink reflex is reflex tearing from parasympathetic innervation to the lacrimal gland. During extreme pain, the corneal reflex is exaggerated, and blepharospasm sometimes occurs such that the eyelids cannot be opened voluntarily. Corneal sensitivity varies by species, region of the cornea, and, in the dog and cat, skull conformation. For example, corneal sensitivity in dogs, as measured by the Cochet–Bonnet esthesiometer and histology of the corneal nerves, was highest, intermediate, and lowest in the dolichocephalic, mesaticephalic, and brachycephalic skull types, respectively. Similarly, the central cornea is less sensitive in brachycephalic cats than domestic shorthair cats. Corneal sensitivity is greatest in the central cornea and lower in the peripheral cornea.
Table 2.3 Elastic moduli of layers of the cornea as determined by atomic force microscopy in rabbits and humans.
| Corneal layer | Elastic modulus (kPa) | |
|---|---|---|
| Rabbit (Thomasy et al., 2014) | Human (Last et al., 2009, 2012) | |
| Epithelium | 0.6 ± 0.3 | Not assessed |
| Anterior basement membrane | 4.5 ± 1.2 | 7.5 ± 4.2 |
| Bowman's layer | Absent | 110 ± 13 |
| Stroma | 1.1 ± 0.6 (anterior) 0.4 ± 0.2 (posterior) | 33 ± 6 (anterior) |
| Descemet's membrane | 12 ± 7.4 | 50 ± 18 |
| Endothelium | 4.1 ± 1.7 | Not assessed |
The cornea is one of the most richly innervated tissues in the body. Most corneal nerve fibers are sensory in origin and respond to mechanical, chemical, and thermal stimuli via the ophthalmic branch of the trigeminal nerve. However, a small proportion of nerves are sympathetic or parasympathetic in origin and derive from the superior cervical ganglion or ciliary ganglion, respectively. Corneal nerve organization is similar across mammalian species, with only minor interspecies differences. All mammalian corneas contain a dense limbal plexus, multiple radially directed stromal nerve bundles, a dense highly anastomotic subepithelial plexus, and a richly innervated epithelium (Figure 2.4). In the dog, corneal innervation arises from the corneal limbal plexus, which comprises a 0.8–1 mm wide, ring‐like band, surrounding the peripheral cornea.
The majority of sensory fibers that innervate the cornea are activated by a variety of exogenous mechanical, chemical, and thermal stimuli, as well as endogenous factors released by tissue injury, and are thus termed polymodal nociceptors. The remainder of the sensory fibers innervating the cornea comprise mechano‐nociceptors and cold thermal receptors, which are only activated in response to mechanical forces or changes in temperature, respectively. In addition to their contributions to corneal protection via the blink reflex and reflex tearing, corneal nerves maintain corneal epithelial health through the secretion of trophic factors and maintenance of basal tear secretions.
Iris and Pupil
Pupillary functions include regulating light entering the posterior segment of the eye, increasing the depth of focus for near vision, and minimizing optical aberrations by the lens. The iris muscles consist of a constrictor (sphincter) that encircles the pupil and radial dilator muscles to expand the pupil. The sphincter muscle is an annular band of smooth muscles near the pupillary margin of the iris and is derived from neural ectoderm. The dilator muscle, also derived from neural ectoderm, consists of a series of myoepithelial cells that extend from near the pupillary margin to the base of the iris and are contiguous posteriorly with the pigmented epithelium (PE) of the ciliary body. Pupil size varies on the basis of the balance between these two muscle groups. The constrictor muscle, which is the stronger of the two, is innervated by the oculomotor nerve (CN III) and provides primarily parasympathetic control; in contrast, the dilator muscle is innervated primarily by sympathetic nerves. The constrictor muscle causes miosis, and the dilator muscle is responsible for mydriasis. Bright light decreases pupil size. The sympathetic activity in the iridal dilator muscle and ciliary body musculature (discussed later) is mediated by a combination of β‐receptors (β1 and β2) and α‐receptors (α1 and α2). Components of the pupillary light reflex are listed in Table 2.4.
Figure 2.4 Schematic of corneal innervation. The limbal plexus is a ring‐like band of predominantly myelinated fibers in the sclera adjacent to the cornea. From the limbal plexus, nerve fibers enter into the corneal stroma as nerve bundles and lose their myelin as they traverse to the central cornea. The subepithelial plexus is a dense, anastomosing network of thin axons immediately underlying the anterior basement membrane. The subepithelial plexus gives rise to the subbasal plexus, a whorl‐shaped network of axons between the anterior basement membrane and basal epithelium where nerve fibers run horizontally as long parallel nerves, termed leashes. The axons of the subbasal plexus then vertically ascend to terminate in various layers of the epithelium.
Species differences of the α‐ and β‐receptors have been demonstrated among humans, rabbits, nonhuman primates, cats, and dogs, and they are summarized in Table 2.5. These receptors alter the effects of drugs on the eye. For example, feline pupils constrict with the use of timolol, a nonselective β‐adrenergic antagonist, because the feline iris sphincter muscle has primarily β‐adrenergic nerve fiber. Because β‐adrenergic nerve fibers are inhibitory to the sphincter muscle, the miosis in response to topically applied timolol is suspected to be the result of its antagonism of inhibitory input to the sphincter muscle. Most synapses in the ciliary ganglion are involved in relaying impulses that result in accommodation; the remainder are concerned with constriction of the pupil. Endogenous prostaglandin F2α appears to be involved in maintaining muscle tone in the sphincter muscle of the iris. Prostaglandins most likely act directly on these muscles, and they appear to act to a lesser extent on the dilator muscles of the canine iris. Exogenous prostaglandin analogues cause miosis in cats, dogs, and horses, and the receptors have been detected in the iris and ciliary body of several mammals. Iris color, or the amount of melanin, influences the effects of many drugs, as melanin can bind drugs, increasing or prolonging their time to onset and duration.
Table 2.4 Components of the pupillary light reflex.
| Stimulus | Illumination of the retina |
|---|---|
| Receptors | Photoreceptors (rods and cones) |
| Afferent pathway | Optic nerve–optic tract to pretectal area (ipsi‐ and contralateral via posterior commissure) |
| Efferent pathway | Pretectal area to the parasympathetic nucleus of CN III (ipsi‐ and contralateral), and then parasympathetic fibers to ciliary ganglion (via CN III) |
