Influence of cyclical mechanical strain on extracellular matrix gene expression in human lamina cribrosa cells in vitro

The lamina cribrosa is a distinct histological region of the optic nerve head (ONH). It is composed of approximately ten perforated (cribriform) connective tissue plates that permit the passage of retinal ganglion cell axons as they exit the ONH [1]. It is a compliant tissue, which in normal human eyes sustains changes in intraocular pressure (IOP) without loss of structural or morphological integrity. This compliance reduces markedly with age due to increased collagen and reduced proteoglycan content in the lamina cribrosa extracellular matrix (ECM) [2,3]. Two important cell types that have been characterized in the lamina cribrosa include the ONH astrocyte and the lamina cribrosa (LC) cell. Both are members of the glial population of the ONH, however, the LC cell, unlike the astrocyte, does not express glial fibrillary acid protein (GFAP) [4]. In terms of morphology, LC cells are broad, flat and polygonal, distinguishing them from the ONH astrocytes which are star shaped [5]. ONH astrocytes are found throughout the ONH and separate the retinal ganglion cell axons from the cribriform plates. The LC cells, in contrast, are localized to the lamina cribrosa region and are situated within or between the cribriform plates [6]. Primary open angle glaucoma (POAG) is a progressive optic neuropathy characterized by raised IOP, retinal ganglion cell (RGC) axon loss, and excavation or cupping of the optic nerve head [7]. It affects over 60 million people worldwide, representing one of the most common causes of irreversible blindness [8]. Electron micrograph and immunohistochemistry studies demonstrate marked disruption to ECM architecture and composition in the glaucomatous lamina cribrosa. This includes backward displacement and distortion of the cribriform plates with increased amounts of collagen VI, elastin, and transforming growth factor-β2 [9-12]. Such ultrastructural changes may adversely affect the biomechanical properties of the lamina cribrosa, predisposing it to collapse as the IOP rises. An obvious consequence of lamina cribrosa collapse is the compression of RGC axons, which arrests their axoplasmic flow. This is clearly demonstrated in models of POAG in monkeys [13]. It is likely that this is also the case in humans ©2005 Molecular Vision