The Three-Dimensional Structure of the Connective Tissue in the Lamina Cribrosa of the Human Optic Nerve Head

Abstract

Comprehensive understanding of the three-dimensional structure of the extracellular matrix (ECM) of the lamina cribrosa is central to understanding its role in health and disease, particularly how changes in configuration might precipitate nerve fibre death in glaucoma. Research until recently has relied almost entirely on light and scanning electron microscopy (SEM) to investigate the ECM of the lamina cribrosa. In this paper, we review the contribution of these methods to current understanding of the three-dimensional structure of the lamina ECM, highlight their potential weaknesses and emphasise that there is still much to be revealed about the structure of the lamina ECM. We then describe our development of confocal microscopy and computer reconstruction as a new and alternative method of investigating the three-dimensional structure of the lamina ECM. We show how optical sectioning allows the confocal microscope to acquire three-dimensional images of the lamina ECM without the degree of tissue disruption associated with preparation for SEM and demonstrate the versatility of analysis of these images by computer reconstructive software. A case is made for confocal microscopy and computer reconstruction contributing to our understanding of this important but complex and delicate structure.

The Effect of Graded Cyclic Stretching on Extracellular Matrix–Related Gene Expression Profiles in Cultured Primary Human Lamina Cribrosa Cells

“…21 LC cells are also believed to reside within or between the connective tissue plates of the LC and are therefore suspected of being important in the ECM response of this tissue to strain. 5,22 Analogous to our findings in LC cells, Hernandez 23 has also shown evidence that astrocytes participate in ONH remodeling. It appears that both intrinsic LC cell types play a role in the glaucomatous changes in the ONH.…”

Age-related changes in the thickness of the human lamina cribrosa

“…Shrinkage from dehydration alone can reduce the extracellular matrix by up to 30%. 12 Our finding of thicknesses about 50% greater than this estimate may arise as a result of our use of hydrated material.…”

The Similarity of Protein Expression in Trabecular Meshwork and Lamina Cribrosa: Implications for Glaucoma

“…In contrast, LC tissue is not actively phagocytic and does not allow passage of extravascular fluid ; instead, it is used to support neural retina axons and allows passage of retinal vasculature and neural ganglion fiber axons through the posterior pole. Within the TM, cells exist as a continuous covering of an open, three-dimensional fibrillar collagen lattice, whereas in the lamina cribrosa, LC cells are enclosed between plates within a compacted extracellular matrix along with astroglia and often insert directly into laminar plates (Anderson, 1969 ;Radius and Gonzales, 1981 ;Alkington et al, 1990 ;Birch et al, 1997 ;Hernandez and Pena, 1997).…”