TL;DR: 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 lAMA's microarchitecture.
Abstract: METHODS. Several models of the optic nerve head tissues (preand 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. (Invest Ophthalmol Vis Sci. 2004;45:4378‐4387) DOI:10.1167/ iovs.04-0133
TL;DR: The results indicate that the basal lamina imposes morphologic stability on the epithelium, while the mesenchyme apparently affects processes involved in changes in morphology, possibly by selective degradation of the basalLamina.
Abstract: The role of the basal lamina in maintaining the normal morphology of mouse embryo submandibular epithelia was assessed by examining its production as well as the cellular and organ culture changes associated with its removal and replacement. The lamina was removed from epithelia isolated free of mesenchyme by brief treatment with testicular hyaluronidase in the absence of calcium. The treatment causes rounding-up of the cells, loss of cellular cohesion, appearance of microvilli, and changes in the organization of cytoskeletal structures. The lamina is not removed and the cellular alterations do not occur in the absence of hyaluronidase in calcium-free medium or when both enzyme and calcium are present, possibly because digestion of chondroitin sulfate, a component of the lamina, is inhibited by calcium. Within 2 h after treatment, in the absence of mesenchyme or biological substrata, the epithelia deposits a new lamina, which is identical by several criteria to the preexisting lamina, and reverses the cellular alterations. Epithelia treated with hyaluronidase lose lobular morphology during culture with mesenchyme. Delaying culture with mesenchyme, to allow restoration of the lamina and of normal cellular architecture, prevents the loss of lobular morphology. The results indicate that the basal lamina imposes morphologic stability on the epithelium, while the mesenchyme apparently affects processes involved in changes in morphology, possibly by selective degradation of the basal lamina.
TL;DR: A revised model of leaf development is proposed with two cell-cycle arrest fronts progressing from the tip to the base: the known primary front, which determines arrest of general cell proliferation, followed by a secondary front that involves PPD and arrests DMC division.
Abstract: Although a complex pattern of interspersed cell proliferation and cell differentiation is known to occur during leaf blade development in eudicot plants, the genetic mechanisms coordinating this growth are unclear. In Arabidopsis, deletion of the PEAPOD (PPD) locus increases leaf lamina size and results in dome-shaped rather than flat leaves. Siliques are also altered in shape because of extra lamina growth. The curvature of a Δppd leaf reflects the difference between excess growth of the lamina and a limitation to the extension capacity of its perimeter. Excess lamina growth in Δppd plants is due to a prolonged phase of dispersed meristematic cell (DMC) proliferation (for example, the meristemoid and procambium cells that form stomatal stem cells and vascular cells, respectively) during blade development. The PPD locus is composed of two homologous genes, PPD1 and PPD2, which encode plant-specific putative DNA-binding proteins. Overexpression of PPD reduces lamina size by promoting the early arrest of DMC proliferation during leaf and silique development. Therefore, by regulating the arrest of DMC proliferation, the PPD genes coordinate tissue growth, modulate lamina size, and limit curvature of the leaf blade. I propose a revised model of leaf development with two cell-cycle arrest fronts progressing from the tip to the base: the known primary front, which determines arrest of general cell proliferation, followed by a secondary front that involves PPD and arrests DMC division.
TL;DR: The mechanical compliance of the human lamina cribrosa decreased with age, suggesting an increased susceptibility to plastic flow and permanent deformation and an age related decrease in resilience.
Abstract: AIMS To investigate changes in the mechanical compliance of ex vivo human lamina cribrosa with age.
METHODS A laser scanning confocal microscope was used to image the surface of the fluorescently labelled lamina cribrosa in cadaver eyes. A method was developed to determine changes in the volume and strain of the lamina cribrosa created by increases in pressure. The ability of the lamina cribrosa to reverse its deformation on removal of pressure was also measured.
RESULTS Volume and strain measurements both demonstrated that the lamina cribrosa increased in stiffness with age and the level of pressure applied. The ability of the lamina cribrosa to regain its original shape and size on removal of pressure appeared to decrease with age, demonstrating an age related decrease in resilience of the lamina cribrosa.
CONCLUSIONS The mechanical compliance of the human lamina cribrosa decreased with age. Misalignment of compliant cribriform plates in a young eye may exert a lesser stress on nerve axons, than that exerted by the rigid plates of an elderly lamina cribrosa. The resilience of the lamina cribrosa also decreased with age, suggesting an increased susceptibility to plastic flow and permanent deformation. Such changes may be of importance in the explanation of age related optic neuropathy in primary open angle glaucoma.
TL;DR: 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 that has been termed the primary site of glaucomatous damage to the optic nerve.
Abstract: 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.