THE ANATOMICAL RECORD 222:95-102 (1988) Nerve Pathways Between the Pterygopalatine Ganglion and Eye in Cats TON LIN, PATRICIA A. GRIMES, AND RICHARD A. STONE Department of Ophthalmology, University of Pennsylvania School of Medicine and Scheie Eye Institute, Philadelphia, PA 19104 ABSTRACT By dissection of thiocholine-stained orbital preparations, it has been determined that three different nerve pathways link the pterygopalatine ganglion and the eye in cats. 1)Nerves from the proximal half of the ganglion join a plexus of nerves and ganglion cells in the rete mirabile of the maxillary artery. Branches of the internal carotid nerve also supply this plexus. Fine nerves from the plexus travel to the optic nerve and then to the eye, accompanying both the nasociliary nerve that passes through the rete and the ciliary arteries that arise from the rete. 2) One or more nerves from the nerve of the pterygoid canal and from a prominent accessory ganglion near the orbital apex course to the inferior optic nerve surface at the optic foramen; these then run distally along the optic nerve to fuse with ciliary nerves or to accompany ciliary arteries entering the eye. 3) Other nerves from the pterygopalatine ganglion travel medially around the extraocular muscle cone to join the ethmoidal and infratrochlear branches of the nasociliary nerve; some nerves from the ganglion then take a retrograde course to the optic nerve, where they join ciliary nerves or arteries to the eye. All three pathways may transmit sympathetic, parasympathetic and somatic sensory nerve fibers. Parasympathetic nerve fibers in the eye arise from two ganglia, the ciliary and pterygopalatine, and from scattered accessory cells. The pterygopalatine ganglion is the most recently recognized of these sources. In rabbits, monkeys, and man, rami orbitales from the pterygopalatine ganglion join branches of the internal carotid nerve to form a retro-orbital plexus surrounding the oculomotor, trochlear, ophthalmic, and abducens nerves just before they enter the orbit (Ruskell, 1965, 1970a). In rabbits and monkeys (Ruskell, 1965, 1970b), fine nerves from this plexus supply the eye. A similar pathway between the pterygopalatine ganglion and the eye has been identified recently in rats (Kuwayama et al., 1987). The pterygopalatine ganglion contains many vasoactive intestinal polypeptide-like (VIP-like) immunoreactive neurons (Uddman et al., 1980a; Hara et al., 1985) and may be a source of VIP nerves found in various cephalic structures, including the eye. In the cat, VIP nerves in the posterior uvea of the eye disappear following extirpation of the pterygopalatine ganglion (Uddmann et al., 1980b), but neural pathways between the ganglion and the eye have not been identified anatomically in this species. To provide a basis for further analysis of the pterygopalatine contribution to the ocular innervation, we describe the results of dissections of the cat orbit that identify three routes by which nerves of the pterygopalatine ganglion reach the eye. METHODS We obtained orbital tissues from 19 cats euthanized under deep chloralose anesthesia as part of unrelated experiments. The cats were perfused through the left 0 1988 ALAN R. LISS, INC. ventricle with 0.85%NaCl solution prior to death. After lateral orbitotomy and craniotomy, the complete orbital contents, including the pterygopalatine ganglion and maxillary nerve, were removed together with the intracranial portions of the second through sixth cranial nerves. The preparations were fixed by immersion in 4% formaldehyde for 30 min and washed overnight in water. After careful removal of extraneous tissue, we stained the preparations by a thiocholine method for detection of cholinesterase activity (Koelle and Friedenwald, 1949) adapted for whole mounts of nerves and ganglia (Gienc, 1977; Kuwayama et al., 1987). The stained tissues were dissected to identify and trace nerves from the pterygopalatine ganglion to the eye. Specimens of the rete mirabile and of some nerves passing from the pterygopalatine ganglion to the eye were dissected from three additional cats for histological examination. The animals, under deep chloralose anesthesia, were perfused with Zamboni’ssolution (Stefanini et al., 1967). The tissues were postfixed in 2% osmium tetroxide, dehydrated in graded alcohols, and embedded in Araldite. Tissue sections, 1or 2 pm thick, were stained with methylene blue-azure B and examined with light microscopy. RESULTS The histochemical method for cholinesterase activity as applied here to partially dissected orbital preparations effectively stains autonomic postganglionic nerves arising from both the pterygopalatine ganglion and the ~ Received November 2, 1987; accepted February 4, 1988. 96 T. LIN ET AL. Internal ethmoidal artery maxillary artery ‘Rete m Ira bile Fig. 1. Drawing of the pterygopalatine ganglion and its nerve pathways to the eye. The rete mirabile is cut away and offset from contiguous structures to allow visualizaiton of all connections. Thiocholine-stained autonomic nerves are represented by thick black lines, and the plexus of fine stained fibers within arterial walls is indicated by cross-hatching. The numbers indicate each of the three pathways from the ganglion to superior cervical sympathetic ganglion. Postganglionic nerves from the ciliary ganglion are not stained, however, presumably because in cats the axons of ciliary ganglion cells are myelinated (Christensen, 1935-1936). Somatic sensory and motor nerves are not stained by this procedure. The histochemical reaction greatly facilitates identification of fine autonomic nerves and microganglia. The pterygopalatine ganglion of the cat rests on the pterygoid muscle that forms the posterior orbital floor, approximately one-third of the way between the apex and inferior margin of the orbit. The ganglion is positioned between the medial orbital wall and the orbital portion of the maxillary nerve and lies just posterolateral to the sphenopalatine foramen. The nerve of the pterygoid canal conveys preganglionic parasympathetic nerves that synapse in the ganglion; it also carries postganglionic sympathetic nerve fibers and possibly sensory fibers of facial nerve origin, both of which pass through the ganglion without synapse. Additional sensory and sympathetic fibers from sphenopalatine branches of the maxillary nerve also traverse the ganglion (Christensen, 1934). Figure 1 diagramatically illustrates and Figure 2 demonstrates the relation of the ganglion and its branches to the maxillary nerve and artery. Large and small nerves from the distal end of the ganglion supply the nose, palate, and anterior orbital structures. Other nerves branching from the proximal end of the ganglion or from the nerve of the pterygoid canal, central to the ganglion, take a retrograde course towards the orbital the eye: 1. Nerves to the rete mirabile. 2. Nerves to the inferior optic nerve sheath. 3. Nerves connecting with terminal branches of the nasociliary nerve. The thin dashed lines show the limits of the extraocular muscle cone, omitted for simplicity. V-1, ophthalmic nerve; V-2, m d lary nerve; Vidian nerve, nerve of the pterygoid canal. apex. These nerves divide and anastamose as they travel caudally and occasionally include small ganglion cell aggregates at the junction points. We identified three pathways by which some of these posteriorly directed nerves reach the eye (Figs. 1, 2). 1 . Nerves to the rete mirabile. As they enter the orbit, the maxillary artery and nerve are surrounded by a large rete mirabile formed from two or three branches of the maxillary artery. Arterial branches leaving the rete communicate with the cranial circulation and also supply the eye (Davis and Story, 1943; Gillilan and Markesbery, 1963). The intraorbital portion of the rete extends from the foramen rotundum to the optic foramen and overlies the nerve of the pterygoid canal as it enters the orbit. Branches from the nerve of the pterygoid canal and nerves from the proximal end of the pterygopalatine ganglion enter the rete and join a complex nerve plexus within it (Fig. 3A). The stained nerves of the plexus divide and anastamose frequently between the rete vessels. Small aggregates of ganglion cells commonly are seen in nerves entering the plexus as well as within the plexus (Fig. 4). In addition, the rete vessels themselves, the maxillary artery, and all arterial branches arising from the rete are invested with a dense intramural plexus of fine stained nerve fibers. Sympathetic nerves also join the nerve network in the arterial rete. Two or more branches of the internal carotid nerve beneath the trigeminal ganglion (Fig. 3B) course forward between the ophthalmic and maxillary nerves and enter the external rete mirabile at its caudal edge. Ramifications of the sympathetic nerves mix with NERVES FROM PTERYGOPALATINE GANGLION TO EYE 97 Fig. 2. Relation of the pterygopalatine ganglion (PPG)to the m d a r y nerve (V-8) and artery on the orbital floor. The proximal portions of the maxillary nerve and artery and the rete mirabile have been dissected away. The numbers indicate the approximate sites of origin of the three nerve pathways to the eye and correspond to those of the drawing in Figure 1. NPC,nerve of the pterygoid canal. Magnification bar, 5 mm. the nerve plexus of the rete. In some preparations, sympathetic nerve branches are seen to join small ganglia located in the caudal portion of the rete. Because of the complexity of the nerve plexus, it is impossible to trace the course of individual nerves inside the rete. Therefore, we could not establish with certainty whether sympathetic nerves link with nerves from the pterygopalatine ganglion, which nerves join with the microganglia of the plexus, or to what extent plexus nerves innervate the arterial walls. However, we observed that fine nerves from the plexus travel to the superior surface of the optic nerve in association with the nasociliary nerve passing through the rete and with the ciliary artery arising from the rete (Fig. 3C). These nerves from the plexus then course anteriorly along the optic nerve to enter the eye. 2. Nerves to the inferior optic nerve sheath. Near the orbital apex there is usually a small mass of ganglion cells associated with the nerve of the pterygoid canal. A branch from this accessory ganglion, together with other nerves running caudally from the pterygopalatine ganglion, takes a dorsal course to the inferior surface of the optic nerve near the optic foramen (Fig. 5). One or more of the nerves accompany the internal ethmoidal artery from the orbit through the optic foramen to the cranial cavity. The remaining nerve or nerves turn to course along the inferior surface of the optic nerve and ultimately enter the eye. 3. Nerves connecting with terminal branches of the nasociliary nerve. As many as 5-10 nerve branches from the pterygopalatine ganglion travel medially under and around the extraocular muscle cone. They join the ethmoidal and infratrochlear branches of the nasociliary nerve that emerge from beneath the medial border of the superior rectus muscle (Fig. 6). Most of the nerves from the pterygopalatine ganglion fuse with or accompany the ethmoidal nerve or, to a lesser extent, the infratrochlear nerve in their peripheral distributions. Some, however, travel centrally along the nasociliary nerve branches to the superior surface of the optic nerve, where they join with ciliary nerves or arteries supplying the eye. Nerves from the pterygopalatine ganglion reaching the optic nerve by all three of these pathways ultimately form an interdigitating network of fine nerves that surround and accompany the ciliary artery; these nerves remain clearly distinct from the intramural innervation of the vessel (Fig. 7). Some of the nerves join ciliary nerves close to the eye, but most enter the globe along the inferior surface of optic nerve with branches of the ciliary artery. The only nerves traveling between the pterygopalatine ganglion and the eye identifiable with certainty in unstained orbital dissections are the nerves on the inferior optic nerve surface. On the basis of histological sections of the optic nerve within the orbital apex region from five orbits of three cats, the number of nerves on the inferior optic nerve surface have been determined to range from two to five. The majority of axons in these nerves are unmyelinated, but 15 of 17 examined nerves contained a modest number of myelinated fibers measuring between 1 p.m and 6 p.m in diameter (Fig. 8). DISCUSSION The fine nerves from the pterygopalatine ganglion that supply the cat eye have not been noted in previous anatomical descriptions of ocular parasympathetic nerves in this animal (Cristensen, 1935-1936; Lele and 98 T. LIN ET AL. Fig. 3. Pathway 1: Nerves to the rete mirabile. A: Nerves from the blood vessels and other nerves in this region. One or more of the symproximal end o f the pterygopalatine ganglion and from the nerve o f the pathetic nerves (arrowhead) pass rostrally to enter the rete mirabile and pterygoid canal enter the rete mirabile, where they join a complex plexus join the nerve plexus within it. C: Nerves (arrowheads) from the plexus of nerves containing microganglia (arrowheads) and isolated ganglion accompany the nasociliary nerve (NCN) and ciliary artery (arrow) as cells. The nerve of the pterygoid canal (arrow) is cut close to the point they leave the rete and travel with them to the optic nerve (ON). 111, at which it enters the orbit. B The internal carotid nerve (arrow) crosses oculomotor nerve; V-1, ophthalmic nerve; V-2, maxillary nerve; V-3, the inferior surface of the trigeminal ganglion and supplies branches to mandibular nerve, VI,abducens nerve. Magnification bars, 1 mm. NERVES FROM PTERYGOPALATINE GANGLION TO EYE Fig. 4. Histological sections of nerves in the rete mirabile. A: Many nerve bundles (arrowheads) are scattered through the connective tissue of the arterial rete. B: A cluster of ganglion cells lie at a nerve junction. 99 A single ganglion cell is present in a very small nerve. Magnification bars: A, 200 pm; B, 50 pm; C, 20 pm. Fig. 5. Pathway 2: Nerves to the inferior optic nerve sheath. A: Branches and fmm a prom(arrows) from the nerve of the pterygoid canal (“(2) inent accessory ganglion (open arrow) near the orbital apex extend to the inferior surface of the optic nerve (ON). Here they turn to travel toward the eye. Other nerves (arrowheads) accompany the interior ethmoidal artery (IEA) fmm the orbit through the optic foramen to the cranial cavity. B Another preparation demonstrates the ofken branching course of nerves from the pterygopalatine ganglion on the inferior surface of the optic nerve. 111, oculomotor nerve; CG, ciliary ganglion; SCN, short ciliary nerve. Magnification bars, 1mm 100 T.LIN ET AL. Fig. 6. Pathway 3 Nerves connecting with terminal branches of the nasociliary nerve. A: Whole mount of M y dissected nerves connecting the distal pterygopalatine ganglion (PPG) and the terminal branches of the nasociliary nerve (NCN). These nerves (between arrows) travel medially from the pterygopalatine ganglion, below and around the extraocular muscle cone, and join the ethmoidal and infratrochlear nerves. B Medial view of a partially disseded preparation. Stained nerves (arrows) fromthe pterygopalatine ganglion (PPG)join the branches of the nasociliary nerve (open arrows). Some fine stained nerves pass back along the nasociliary nerve to reach the superior surface of the optic nerve (ON). NPC, nerve of the pterygoid canal. C: The nasociliary nerve is lifted away from the superior surface of the optic nerve. A small stained nerve (arrows) transfers from the nasociliary nerve to the optic nerve sheath, where it joins other nerves directed to the eye. Additional nerves (arrowhead)from the pterygopalatine ganglion are visible on the inferior optic nerve sheath. CA, ciliary artery. Magtllfication bars: A, 5 m;B, C, 0.5 mm. Weddell, 1959; Grimes and von Sallmann, 1960). The The pathways by which nerves from the pterygopaomission is not surprising, because these nerves do not latine ganglion reach the optic nerve in the cat are stain by the silver method used as a dissection aid in circuitous and differ from those described in other the earlier studies (Ruskell, 1965; Kuwayama et al., mammalian species. In comparison to cats, the ptery1987), and they are too fine to be evident in unstained gopalatine ganglia of monkeys (Ruskell, 1970a),rabbits (Ruskell, 1965), and rats (Kuwayama et al., 1987) lie preparations. NERVES FROM PTERYGOPALATINE GANGLION TO EYE Fig. 7. Final common pathway. Near the eye, nerves traveling from the pterygopalatine ganglion by all three paths form a network of tine nerves that surrounds and accomuanies the ciliary artery (CA) but is distinct fmm its intramural innekation. All of these nerves enter the eye with branches of the ciliary artery or &r joining ciliary nerves, The nmbers, correspondingto those in Figure 1, indicate the pathways by which the labeled nerves reach the optic nerve. SCN,short nerves. Magmfkation bar, 1 mm. 101 Fig. 8. A, B Cross sections of representative nerves originating from the PteWZOPalatine g a d i o n on the inferior surface of the optic nerve. These nerves, taken from two different eyes, contain mostly unmyelinated nerve fibers but also a few myelinated axons. Magnification bar, 10 um. NasociIiar\j nerve Pterygopalatine pterygoid canal nerve Ganglion cells in Rete Fig. 9. Schematic diagram illustrating the nerve pathways between the pterygopalatine ganglion and the eye in cats. The numbering of the pathways corresponds to that in Figure 1. 102 T. LIN ET AL. closer to the cranial nerves in the orbital fissure, and Roland and Marianne E. Sargent Teaching and Retheir orbital branches travel a relatively short distance search Fund of the Scheie Eye Institute. to join the retro-orbital nerve plexus formed around the LITERATURE CITED cranial nerves. Nerves from the retro-orbital plexus disChristensen, K 1934 The innervation of the nasal mucosa, with special tribute to orbital structures along the paths taken by reference to its afferent supply. Ann. Otolaryngol., 43:1066-1083. the cranial nerves. The unusual pathways in the cat Christensen, K 1935-1936 Sympathetic and parasympathetic nerves presumably are dictated by the position of the ganglion, in the orbit of the cat. J. Anat., 70:225-233. well within the orbit and at a considerable distance Davis, D.D., and H.E. Story 1943 Carotid circulation in the domestic cat. Publ. Field Mus., Zool. Ser., 28:l-47. from the entry site of the cranial nerves. J. 1977 The application of histochemical method in the anatomThe extensive nerve plexus in the rete mirabile of the Gienc, ical studies on the oarasvmoathetic eanelia and nerve bundles of cat may be analogous to the retro-orbital plexus idenpostganglionicaxonsin th;! siblingual&gi& of some mammals. 2001. tifed in the other mammals. Like the retro-orbital plexus, Pnl.., 2fi:187-192. - - ~- --the rete plexus is supplied by nerves from the ptery- Gillill, L.A. and W.R. Markesbery 1963 Arteriovenous shunts in the blood supply to the brains of some common laboratory animalsgopalatine ganglion and the superior cervical sympawith special attention to the rete mimbik conjugaturn in the cat. J. thetic ganglion, it contains small aggregates of ganglion Comp. Neurol., 121:305-311. cells, and it sends some nerves to the eye. Grimes, P.A., and L. von Sallmann 1960 Comparative anatomy of the ciliary nerves. Arch. Ophthalmol., 64:81-91. The pathways from the pterygopalatine ganglion to H., G. Hamill, and D. Jacobowitz 1985 Origin of cholinergic the eye are illustrated schematically in Figure 9. On Hara, nerves to the rat major cerebral arteries: Coexistencewith vasoactive the basis of the anatomical connections, all of these intestinal polypeptide. Brain Res. Bull., 14:179-188. pathways may carry postganglionic sympathetic, para- Koelle, G. and J. Friedenwald 1949 A histochemical method for localizing cholinesterase activity. Proc. Soc. Exp. Biol. Med. 70:617-622. sympathetic, and/or somatic sensory nerve fibers. Nerves Y., P.A. Grimes, B. Ponte and R.A. Stone 1987 Autonomic from the pterygopalatine ganglion to the eyes of mon- Kuwayama, neurons supplying the rat eye and the intraorbital distribution of keys, rabbits, and rats (Ruskell, 1965, 1970a; Kuwayvasoactive intestinal polypeptide (VIPhlike immunoreactivity. Exp. ama et al., 1987) also potentially transmit fibers of the Eye Res., 44:907-922. same mixed origin. In monkeys, however, Ruskell (1970a, Lele, P.P. and G. Weddell 1959 Sensory nerves of the cornea and cutaneous sensibility. Exp. Neurol. 1:334-359. b, 1974) has shown that nerves from the pterygopalaRuskell, G.L. 1965 The orbital distribution of the sphenopalatine gantine ganglion to the retro-orbital plexus and nerves from glion in the rabbit. In The Structure of the Eye, Vol. 2: Symposium. the retro-orbital plexus to the eye are composed preEighth International Congress of Anatomists, Wiesbaden. J. Rohen, ed. Schattauer, Stuttgart, pp. 355-368. dominantly of unmyelinated parasympathetic fibers originating in the pterygopalatine ganglion together with Ruskell, G.L. 1970a The orbital branches of the pterygopalatine ganglion and their relationship with internal carotid nerve branches in a few myelinated fibers possibly from the maxillary primates. J. Anat., 106:323-329. nerve. Our histological examination of some of the ocu- Ruskell, G.L. 1970b A n ocular parasympathetic nerve pathway of facial nerve origin and its influence on intraocular pressure. Exp. Eye Res., lar nerves from the pterygopalatine ganglion in cats 10:319-330. indicates that they also carry predominantly unmyeG.L. 1974 Ocular fibers of the maxillary nerve in monkeys. J. linated fibers together with some myelinated axons, but Ruskell, Anat., 118:195-203. the proportion of sympathetic and parasympathetic fi- Btefanini, M., C. De Martino, and L. Zamboni 1967 Fixation of ejaculated spermatozoa for electron microscopy. Nature, 216:173-174. bers and the source of the myelinated nerve fibers reUddman, R., L. Malm, and F. Sundler 1980a The origin of vasoactive main to determined. ACKNOWLEDGMENTS This study was supported by National Institute of Health grants EY-05454 and EY-03444 and by the F. intestinal polypeptide (VIP) nerves in the feline nasal mucosa. Acta Otolar~ng~l., 89:152-156. Uddman, R., J. Alumets, B. Ehinger, R. Hakanson, I. Loren, and F. Sundler 1980b Vasoadive intestinal peptide nerves in ocular and orbital structures of the cat. Invest. Ophthalmol. Vis. Sci., 19:878885.