Vasoactive intestinal and calcitonin gene-related peptides,tyrosine hydroxylase and nitrergic markers in the innervation of the rat central retinal artery

The vascular supply of the optic nerve has been studied with different methods including corrosion casts both in humans and in other mammals. In man, primates and some other mammals, such as the rat, a distinct central retinal artery accompanies the optic nerve, and runs through the lamina cribosa to reach the optic nerve head. Similarities between human and rat central retinal artery could serve to understand changes in the autonomic perivascular innervation in glaucoma using the rat as an animal model. Nitric oxide, calcitonin gene-related peptide, neuropeptide Y, substance P and vasoactive intestinal peptide have been identified around the monkey central retina artery. Innervation of the rat central artery, however, has not been described in detail. Using immuno- and histochemical methods, the present study investigates the peptidergic, adrenergic and nitrergic innervation of the rat posterior ciliary artery as well as the central retina artery. Numerous nitric oxide positive nerve fibers were visualized posterior and anterior to the lamina cribosa of the optic nerve. They colocalized with NADPH-diaphorase positive fibers, which could also be observed in two of six specimens studied at the level of the optic nerve head. Calcitonin gene-related peptide, tyrosine hydroxylase, and VIP positive fibers were also observed surrounding the vessels of the rat optic nerve. The presence of neuronal nitric oxide/NADPH-diaphorase and vasoactive intestinal peptide positive nerve fibers surrounding the posterior ciliary and central retinal arteries indicates a vasodilator effect in the rat optic nerve. Tyrosine hydroxylase positive innervation indicates the presence of sympathetic activity, and calcitonin gene-related peptide positive fibers indicate sensory innervation by trigeminal primary efferents.     

Optic nerve microcirculation. III. Lamina cribrosa

The architecture of the lamina cribrosa was investigated on the material of 160 optic nerves of people decreased at the age of 6 months to 80 years, free of pathological changes of circulation. The posterior segment of lamina cribrosa is supplied by arterial blood from: centripetal arterioles of the pia mater, ramifications from the secondary and tertiary posterior short ciliary arteries and from the longitudinal net of capillaries of the optic nerve. The central part of the lamina cribrosa is supplied by the twigs of the complete or incomplete vascular ring of Zinn-Haller or directly from secondary twigs of choroidal arteries. The anterior part of lamina cribrosa is vascularized by choroidal vessels and in a minor part by the vascular ring of Zinn-Haller. The circulation in the area of lamina cribrosa is integrally connected with the system of posterior short ciliary arteries and the arterioles of the internal vagina of the optic nerve. The central retinal artery does not give up any branches in this region. Similarly to other segments of the optic nerve there exists an individual variability in the system and course of the vessels in the lamina cribrosa. The vascular system of lamina cribrosa is connected anteriorly with the vessels of the paralaminar area of the optic disc which receive vascular branches from early ramifications of the central retinal artery (25 p.c. of cases).     

Morphology and neurochemistry of canine corneal innervation

PURPOSE: To determine the architectural pattern and neuropeptide content of canine corneal innervation. METHODS: Corneal nerve fibers in normal dog eyes were labeled immunohistochemically with antibodies against protein gene product (PGP)-9.5, calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), and tyrosine hydroxylase (TH). Relative innervation densities and distribution patterns for each fiber population were assessed qualitatively by serial line-drawing reconstructions and quantitatively by computer-assisted analyses. RESULTS: More than 99% of all corneal PGP-9.5-immunoreactive (IR) nerves contained both CGRP and SP, approximately 30% contained TH, and none contained VIP. Distribution patterns of corneal PGP-9.5-, CGRP-, SP-, and TH-IR nerves were indistinguishable, except that TH-IR fibers were absent from the corneal epithelium. Morphologically, canine corneal innervation consisted of a rich anterior stromal plexus, divided on the basis of morphologic criteria into anterior and posterior levels, and a rich epithelial innervation, characterized by large numbers of horizontally oriented, basal epithelial "leash" formations. Leash axons in all quadrants of the corneal epithelium oriented preferentially toward a common locus in the perilimbal cornea. CONCLUSIONS: The results of this study demonstrate for the first time the detailed architectural features, distinctive basal epithelial leash orientations, and peptidergic content of canine corneal innervation. The normal innervation pattern described in this study will provide other investigators with essential baseline data for assessing corneal nerve alterations in canine patients with spontaneous chronic corneal epithelial defects (SCCED) and other ocular diseases or injuries.     

Angioarchitecture and innervation of the primate anterior episclera

PURPOSE: To investigate the primate episcleral vasculature and its innervation with respect to morphological specializations. METHODS: Serial sections of the anterior episclera of 8 monkey eyes and 20 human eyes were investigated enzyme- and immunohistochemically using antibodies against smooth-muscle alpha-actin (SMA), neurofilament, synaptophysin, substance P (SP), calcitonin gene-related peptide (CGRP), vesicular acetylcholine transporter (VACHT), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), vesicular monoamine transporter II (VMAT II), as well as the NADPH-diaphorase reaction. Arteriovenous anastomoses (AVA) were quantified. RESULTS: All episcleral vessels including veins showed intense staining for SMA. Capillary loops were only seen in the limbal arcades, not in the episclera itself. Instead, AVA connected the episcleral arteries with the veins, which formed an interlacing vascular network. In the monkey episclera, 4-6/mm2 AVA were found; in the human episclera, 0.5-1/mm2. Numerous nerve endings staining for NADPHd (NADPHdiaphorase) and TH surrounded all episcleral vessels including anastomoses and veins. NPY, VIP, and VACHT-immunoreactive (IR) nerve terminals were less numerous. CGRP and SP-IR terminals were seen both at the vessels and in the intervascular connective tissue. CONCLUSIONS: The episcleral vasculature shows a specialized morphology with absence of capillaries, numerous arteriovenous anastomoses, a muscle-rich venous network, and intense innervation by vasodilative and vasoconstrictive nerves. This might allow regulation of blood flow and volume in the episcleral vessels and Voigt's capillaries for thermoregulation and modulation of episcleral venous pressure and thereby outflow facility.     

Thickness of the lamina cribrosa and peripapillary sclera in Rhesus monkeys with nonglaucomatous or glaucomatous optic neuropathy

Purpose: To measure the thickness of the lamina cribrosa and peripapillary sclera in monkeys with a nonglaucomatous optic nerve damage and to compare that with those of monkeys with glaucomatous optic neuropathy. Methods: The study included 22 monkey eyes (Macaca mulatta) which had undergone a temporary experimental central retinal artery occlusion (CRAO) and seven monkey eyes in which experimental glaucoma was unilaterally produced. We measured histomorphometrically the thickness of the lamina cribrosa and peripapillary sclera. Results: The lamina cribrosa was significantly thicker in the CRAO group than in the glaucoma group (central region: 212 ± 46 μm versus 167 ± 17 μm; p = 0.009). The thickness of the peripapillary sclera at the optic disc border (253 ± 39 μm versus 192 ± 21 μm; p = 0.001) and outside of the optic nerve meninges (408 ± 70 μm versus 314 ± 64 μm; p = 0.006) was significantly greater in the CRAO group. Conclusions: In monkey eyes with a temporary CRAO as a model for nonglaucomatous optic nerve damage, the lamina cribrosa is significantly thicker than in monkey eyes with experimental glaucomatous optic nerve damage. It may suggest that the loss of optic nerve fibres might not be the reason for the thinning of the lamina cribrosa in eyes with advanced glaucoma. The thinner peripapillary sclera in the glaucomatous eyes may suggest that the monkey sclera is more vulnerable to stretching with increased intraocular pressure than the human eye for which no glaucoma‐related lengthening of the eyeball and thinning of the peripapillary sclera have been observed.     

A "throttle" mechanism in the central retinal vein in the region of the lamina cribrosa

AIMS: To demonstrate a constriction in the central retinal vein in the region of the lamina cribrosa. METHODS: A prospective comparative interventional study of 13 controls and 19 patients with central retinal vein occlusion (CRVO) using colour Doppler imaging of the central retinal artery and vein in the region of the lamina cribrosa and optic nerve posterior to the globe. RESULTS: In controls peak velocities in the vein were higher in the region of the lamina cribrosa than the optic nerve, mean 175 mm/second (mm/s) and 49 mm/s respectively, p<0.0001. The velocities in the artery were also higher in the region of the lamina cribrosa, mean 122 mm/s and 92 mm/s, p = 0.007. The variability of the velocities in the region of the lamina cribrosa was 7.4% in the artery and 15.2% in the vein. The mean ratio of the velocities in the vein (4.2 (SD 2.1)) was significantly higher than the mean ratio in the artery (1.4 (SD 0.4), p<0.0001). In CRVO, the mean ratio in the vein was lower in the affected eyes (2.2 (SD 1.9), p<0.01) and fellow unaffected eyes (2.2 (SD 1.0), p = 0.003) than controls. The values were stable in eight after radial optic neurotomy. CONCLUSION: The presence of a constriction of the vein in the region of the lamina cribrosa can be inferred from the presence of higher blood velocities at this site than further back in the optic nerve. In CRVO there may be a more uniform narrowing of the vein along its course in the nerve. Neurotomy did not affect the measurements.     

Angioarchitecture of intraorbital part of human optic nerve

The distribution of blood vessels in the intraorbital part of the human optic nerve was examined after injecting silicone rubber into the ophthalmic artery of eyes obtained after autopsy. Particular attention was focused on the possible existence of an end artery which might play an important role in ischemic optic neuropathy. In the anterior part of the optic nerve, the vascular architecture consisted of axial and peripheral vascular systems. The axial system was constituted of intraneural branches of the central retinal artery. The peripheral system was mostly branches derived from the intravaginal part of the central retinal artery. Few branches of the posterior ciliary arteries extending to the optic nerve were observed in this part. In the posterior part of the optic nerve, the vascular architecture was formed mostly by the peripheral system which consisted of the extravaginal and recurrent intravaginal branches of the central retinal artery and branches of the ophthalmic artery. These branches forming the peripheral system anastomosed with each other on the surface of the optic nerve. Within the anterior part of the optic nerve, intraneural branches of the central retinal artery and centripetal branches of the pial plexus anastomosed and formed a fine vascular network. The density of the intraneural vascular meshwork was sparse in the lamina cribrosa and the posterior part of the optic nerve. On the surface of the optic nerve and in its inner part, blood vessels anastomosed and formed a network: no end arteries appeared to exist.     

Association of systemic cardio-vasculature status with retinal vascular endothelium in diabetes

The relationship between diabetic retinopathy and macro-vascular complications in diabetes suggests a pathogenic association between these conditions. Vascular endothelium has been identified as a main site of blood vessel injury in diabetes. Diabetic retinopathy is associated with systemic arterial stiffness and altered vascular endothelium function and structure. Retinal vasculature endothelium at the macula, arterio-venous crossings, and in the optic nerve at the lamina cribrosa region is reported to differ from the endothelium in the rest of the retinal blood vessels. The central retinal artery and vein are in close proximity in the optic nerve where they share a common adventitia; thus, increased arterial wall stiffness and thickness may affect blood flow in the neighboring central retinal vein in this region. Moreover, increased arterial stiffness in small arterial beds is associated with retinal venular widening; it suggests the possibility of central retinal artery compressing the central retinal vein at the lamina cribrosa, thereby compromising venular outflow in the retina of diabetic patients. Altered blood flow in the central retinal vein in the postlaminar region has been detected in patients who experience progression of diabetic retinopathy. Increased hydrostatic pressure in the central retinal vein may play a major role in the pathogenesis of diabetic retinopathy. The aim of this review article is to emphasize this pathogenetic mechanism that has often been overlooked.     

心血管状况与糖尿病视网膜血管内皮细胞的相关性

糖尿病视网膜病变及其并发大血管病变表明两者之间致病存在相关性.血管内皮细胞是糖尿病血管损伤的主要部位.糖尿病视网膜病变能并发全身动脉硬化和改变血管内皮的功能及结构.在黄斑,动静脉交叉处和在筛板区视神经中的视网膜血管内皮细胞不同与其余视网膜血管中内皮细胞.中央视网膜在视神经中动脉和静脉非常接近且共用同一外膜;因此,增加动脉壁的硬度和厚度可以影响该区域中的相邻中央视网膜静脉中的血流量.此外,小动脉床中的动脉硬化加剧与视网膜微血管扩张有关;这表明筛板中视网膜中央动脉压迫视网膜中央静脉的可能性,从而损害糖尿病患者视网膜中的小静脉流出.经观察发现糖尿病视网膜病变患者在后层流区的视网膜中央静脉中的血流量发生改变.在视网膜中央静脉中增加静水压可能在糖尿病视网膜病变的病情进展过程中起重要作用.这篇综述文章的主旨是强调这种常常被忽视的发病机制.     

Morphology of the murine optic nerve

PURPOSE: To study the morphology of the murine optic nerve (ON). METHODS: Eyes of C57/Bl6 and BalbC mice were studied by light and electron microscopy. Microvascular castings of the ON region were prepared by transcardial injection of liquid plastic and studied with a scanning electron microscope. Immunohistochemistry was performed using antibodies against glial fibrillary acidic protein (GFAP), connexin 43, carbonic anhydrase II, and collagen types I and III. RESULTS: The transition between nonmyelinated and myelinated portion of the ON started approximately 0.6 mm behind the globe. A lamina cribrosa was completely absent. Instead, ON axons passed through a scleral hole that was surrounded by a ring of type III and type I collagen fibers. Instead of connective tissue beams within the nerve, layers of elongated astrocytes traversed the ON. All astrocytes stained for GFAP, but not for carbonic anhydrase II. The arterial supply of the nonmyelinated ON derived from branches of the central retinal artery. None of the capillaries derived from choroidal vessels. CONCLUSIONS: The mouse ON head differs from that of other species, because it lacks a lamina cribrosa and a choroidal vascular supply. Studies in glaucomatous mice might help to identify the importance of the lamina cribrosa and the choroidal vascular supply for optic nerve damage in glaucoma.     

Morphometry of the human lamina cribrosa surface

The lamina cribrosa is a sieve-like perforation in the posterior part of the sclera, that allows passage of the retinal ganglion cell axons and central retinal vessels and preserves a pressure gradient between the intraocular and extraocular space. It has been termed the primary site of glaucomatous damage to the optic nerve. Using electron microscopy, the authors morphometrically evaluated the inner surface of the lamina cribosa in 40 normal human donor eyes. There were 14 men and 21 women with a mean age of 52 +/- 22 yr (10-82 yr). Mean single pore area (0.004 +/- 0.001 mm2) and summed pore area were significantly (P less than 0.05) larger and the ratio of summed pore area to lamina area was higher in the inferior and superior regions than in the temporal and nasal regions. The ratio decreased with increasing lamina cribrosa size. Count, size, form, and density of the pores were statistically independent of age, sex, side, and lamina cribrosa form. Pore count and summed pore area (mean: 0.92 +/- 0.22 mm2) increased significantly with enlarging lamina cribrosa size. The area of the lamina cribrosa openings for passage of the central retinal vessels was independent of the lamina cribrosa size. The high ratio of summed pore area to lamina area and the large single pore area may be pathogenetically important for the increased glaucoma susceptibility in the inferior and superior disc regions. The lack of a correlation between lamina cribrosa size and the area of the lamina cribrosa openings for the retinal vessels may explain why central retinal vessel occlusions occur independently of optic disc size.     

Collagen fibrillar network in the optic nerve head of normal monkey eyes and monkey eyes with laser-induced glaucoma--a scanning electron microscopic study

PURPOSE: To examine the three-dimensional organization of collagen fibrils in the lamina cribrosa of normal monkey eyes and monkey eyes with laser-induced glaucoma. METHODS: Intraocular pressure elevation and glaucomatous optic discs were obtained in one eye of three adult monkeys by repeated applications of argon laser to the chamber angle. The monkey eyes were enucleated, and the collagen fibrillar network was investigated by scanning electron microscopy after cell maceration with 10% sodium hydroxide and conductive staining. RESULTS: In normal monkey eyes, round to oval shaped regular laminar pores through which axon bundles exited were observed in the lamina cribrosa. The straight, column-like pores or openings were formed by multilayered laminar plates that aligned vertically in parallel with the optic nerves. The surface of the laminar plates was covered by delicate, loosely arranged collagen fibrils. The inner surface of the pores was smooth, made up of well-packed collagen fibers. In glaucomatous eyes, the laminar pores were clogged by tightened collagen fibrils. The inner surface of the pores was irregular, and the pores were narrowed or distorted. CONCLUSIONS: Alterations in the three-dimensional organization of collagen fibrils were demonstrated in the optic nerve head of glaucomatous monkey eyes. The architectural changes may affect the flexibility and resilience required of the lamina cribrosa in supporting optic nerve fibers.     

Medullated retinal nerve fibers: speculations on their cause and presentation of cases

Twelve patients with medullated retinal nerve fibers are presented. The paper discusses the possible roles played by formation of the ganglion cell axons and lamina cribrosa in the development of medullated retinal nerve fibers. In addition to myopia and amblyopia, patients with medullated retinal nerve fibers may show unusual lens tilts, anterior chamber anomalies, unexpected field losses, and unusual direction of the optic nerve.     

Distribution and expression of transforming growth factor-beta and platelet-derived growth factor in the normal and glaucomatous monkey optic nerve heads.

PURPOSE: Remodeling of the extracellular matrix occurs in the lamina cribrosa in progressed glaucomatous optic nerve damage including disc cupping. We examined immunohistochemical changes in the transforming growth factor (TGF)-beta and platelet-derived growth factor (PDGF) in the optic nerve head in an experimentally induced glaucoma model. METHODS: We used 3 cynomolgus and 2 Japanese monkey eyes. Glaucoma was induced by repeated argon laser photocoagulation of the chamber angle. Eyes were enucleated after disc cupping had formed 3 to 5 months after photocoagulation. The optic nerve head was examined for expression of TGF-beta1, -beta2 and -beta3 and PDGF-A and -B in frozen sections and by the biotin ExtraAvidin-alkali phosphatase method. RESULTS: Normal monkey eyes showed TGF-beta1, -beta2 and -beta3, and PDGF-A and -B in the optic nerve head including the nerve fibers, glial cells, and vascular cells. Glaucomatous eyes showed stronger expression of TGF-beta1 and -beta2 in the glial cells around the lamina cribrosa. The staining intensities for TGF-beta3, PDGF-A and -B were the same as in normal eyes. CONCLUSIONS: Eyes with experimental glaucoma showed higher expression of TGF-beta1 and -beta2 around the lamina cribrosa. These findings may show upregulation of extracellular matrix production as related to remodeling of the lamina cribrosa in glaucoma.     

Changes in transforming growth factor-beta and platelet-derived growth factor in the optic nerve head in monkey experimental glaucoma

PURPOSE: Remodeling of the extracellular matrix occurs in the lamina cribrosa in progressed glaucomatous optic nerve damage including disc cupping. We examined immunohistochemical changes in the transforming growth factor (TGF)-beta and platelet derived growth factor (PDGF) in the optic nerve heads in experimentally induced glaucoma. METHODS: We used 3 cynomolgus and 2 Japanese monkey eyes. Glaucoma was induced by repeated argon laser photocoagulation of the chamber angle. Eyes were enucleated after disc cupping had formed 3 to 5 months after treatment. The optic nerve head was examined for expression of TGF beta 1, beta 2, and beta 3, and PDGF A and B in frozen sections and by the biotin-ExtrAvidin-Alkali Phosphatase method. FINDINGS: Normal monkey eyes showed TGF beta 1, beta 2, and beta 3, and PDGF A, and B in the optic nerve head including the nerve fibers, glial cells, and vascular cells. Glaucomatous eyes showed stronger expression of TGF beta 1 and beta 2 in the glial cells around the lamina cribrosa. The staining intensities for TGF beta 3, PDGF A, and PDGF B were the same as in normal eyes. CONCLUSION: Eyes with experimental glaucoma showed higher expressions of TGF beta 1 and beta 2 around the lamina cribrosa. This finding may show upregulation of extracellular matrix production as related to remodeling of the lamina cribrosa in glaucoma.     

Substance P-like immunoreactivity in the central retinal artery of the rabbit

Substance P-like immunoreactive nerve fibers were identified in the central retinal artery of the rabbit using the peroxidase-antiperoxidase method. The fibers were seen to encircle the central retinal artery throughout its course in the main trunk of the optic nerve. No labeled fibers were seen in the central retinal vein or in the retinal blood vessels. It appears, therefore, that the central retinal artery and the retinal blood vessels are innervated by different nerve systems: the central retinal artery by one of the peripheral nerves, and the retinal vessels by the central nervous system.     

Immunocytochemical and ultrastructural evaluation of the distribution of nervous tissue and neuropeptides in the meibomian gland

Background: The ultrastructure of the meibomian gland, of its innervation and the localization of neuropeptides in the glandular tissue of the guinea pig and humans are incompletely known. Therefore they have been investigated in the present study. Methods: The ultrastructure of the tissue was examined using standard transmission electron microscopic techniques. Additional scanning electron microscopy was carried out on rabbit tissue. Antisera against the neuronal marker protein gene product were used to demonstrate the distribution pattern of the nerve fibers. The neuropeptides substance P (SP) and neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) and the neuronal enzyme tyrosine hydroxylase (TH) were identified by their specific antisera. Results: The glands were found to be composed of arrays of alveoli. The outer cells of the alveoli form a germinal layer. Toward the inside of the alveolus the cells are laden with a secretory substance. The cells disintegrate as they approach the excretory duct. Nerve fibers from a plexus around the alveoli. These nerve fibers form synapses à distance to the basal alveolar cells and enter the basal lamina of the capillaries. In guinea pigs many nerve fibers were positive for the neuropeptides SP and NPY and for VIP, and fewer for CGRP and TH; in humans only SP and CGRP were demonstrated. Conclusion: Both the density of nerve fibers and the presence of various neuropeptides suggest that the stimulation of the meibomian gland is subject to nervous control.Presented at the Joint European Research Meetings in Ophthalmology and Vision (JERMOV), October 1995, Montpellier, France     

The extracellular matrix composition of the monkey optic nerve head

The presence and distribution of laminin, heparan sulfate proteoglycan and collagen types I, III and IV were immunohistologically determined in cynomolgus monkey optic nerve heads using the avidin-biotin-peroxidase complex technique. Collagen types I and III were detected within the collagenous plates of the scleral lamina cribrosa, in the septa and pia mater of the postlaminar optic nerve and in blood vessel walls in all regions of the optic nerve head. Collagen type IV, laminin and heparan sulfate proteoglycans were all localized to the margins of the collagenous laminar plates of the scleral lamina cribrosa and along the margins of the optic nerve septa and the pia mater. All three components also appeared beneath the blood vessel endothelium throughout the optic nerve head. Within the lamina cribrosa, collagen types I and III occupy the core of the scleral laminar plates and may provide structural support for optic nerve bundles exiting the eye. The distribution of collagen type IV, laminin and heparan sulfate proteoglycan corresponds to basement membranes from two sources: vascular endothelial cells and glial cells lining the axonal bundles. Abnormalities of these substances may influence optic nerve function and susceptibility to elevated intraocular pressure by altering their mechanical support functions within the nerve head, by interfering with axonal nutrition, or both.     

Acute ischemic atrophy of papilla disc and diabetes

Acute ischemic neuropathy is the acute ischemic necrosis of the optic nerve fibers occurred by the occlusion of small vessels which distribute widely to lamina cribrosa and anterior et posterior area of lamina cribrosa. Pale coloured edema and light swelling are seen generally on the optic disc, and after a few months falls in simplex nerve atrophy. I have explained my 3 cases of ischemic neuropathies. They have some things in common, and causes are considered arteriosclerosis or temporal arteritis in old people, and often takes place based on diabetes mellitus, lupus erythematosis or another many diseases etiologically.     

Finite element modeling of optic nerve head biomechanics

PURPOSE: Biomechanical factors have been implicated in the development of glaucomatous optic neuropathy, particularly at the level of the lamina cribrosa. The goal of this study was to characterize the biomechanics of the optic nerve head using computer modeling techniques. METHODS: Several models of the optic nerve head tissues (pre- and postlaminar neural tissue, lamina cribrosa, central retinal vessel, sclera, and pia mater) were constructed. Stresses, deformations, and strains were computed using finite element modeling for a range of normal and elevated intraocular pressures. Computed retinal surface deformations were compared with measured deformation patterns in enucleated human eyes. A sensitivity analysis was performed in which tissue properties and selected geometric features were varied. RESULTS: Acute IOP-induced deformation of the vitreoretinal interface was highly dependent on optic cup shape but showed a characteristic "W-shaped" profile that did not match the deformation of the anterior surface of the lamina cribrosa. The central retinal vasculature had surprisingly little effect on optic nerve head biomechanics. At an IOP of 50 mm Hg, strains (fractional elongation) in the lamina cribrosa averaged 4% to 5.5%, dependent on model geometry, with maximum strains up to 7.7%. Strains in the lamina cribrosa were more dependent on scleral stiffness, scleral thickness, and scleral canal diameter than on lamina cribrosa stiffness and optic cup shape. CONCLUSIONS: Computed levels of strain in the lamina cribrosa are biologically significant and capable of contributing to the development of glaucomatous optic neuropathy, even without considering the probable accentuating effect of the lamina cribrosa's microarchitecture. Depending on optic cup shape, IOP-induced deformation of the vitreoretinal interface may not match lamina cribrosa deformation. This finding implies that scanning laser tomography has limited ability to estimate lamina cribrosa deformation when imaging the anterior topography of the optic nerve head. Biomechanical effects in the lamina cribrosa depend strongly on scleral properties.