Life under pressure: The role of ocular cribriform cells in preventing glaucoma

Abstract

Primary open-angle glaucoma is a multifactorial blinding disease often impacting the two pressure-sensitive regions of the eye: the conventional outflow pathway and the optic nerve head (ONH). The connective tissues that span these two openings in the globe are the trabecular meshwork of the conventional outflow pathway and the lamina cribrosa of the ONH. Resident cribiform cells of these two regions are responsible for actively remodeling and maintaining their connective tissues. In glaucoma, aberrant maintenance of the juxtacanalicular tissues (JCT) of the conventional outflow pathway results in ocular hypertension and pathological remodeling of the lamina cribrosa results in ONH cupping, damaging retinal ganglion cell axons. Interestingly, cells cultured from the lamina cribrosa and the JCT of the trabecular meshwork have similarities regarding gene expression, protein production, plus cellular responses to growth factors and mechanical stimuli. This review compares and contrasts the current knowledge of these two cell types, whose health is critical for protecting the eye from glaucomatous changes. In response to pressure gradients across their respective cribiform tissues, the goal is to better understand and differentiate healthy from pathological behavior of these two cell types.

Anatomy of the Human Optic Nerve: Structure and Function

“…Although LC cells reside within the LC, astrocytes GFAP (+) are located in the plate openings alongside axon bundles as they transverse multiple plates [66,71]. Ultrastructural evaluations show that LC cells are elongated with abundant cytoplasmic actin microfilaments and organelles, such as an active rough endoplasmic reticulum, a well-developed Golgi apparatus and a dense band of heterochromatin along the nuclear membrane [77]. LC cells produce an increased expression of extracellular matrix (ECM) proteins if exposed to mechanical stimulation [78].…”

“…Regarding their embryonic origin, the glial elements of the ONH are derived from ectodermal cells, but the mesenchymal cells of neural crest account for the development of the LC tissue and cells [77].…”

Roles of exosomes in the normal and diseased eye

“…Both of these tissues display signs of fibrosis and/or changes in biochemical, morphological and mechanical properties of the ECM (Hernandez et al, 1990; Overby et al, 2014; Paula et al, 2016; Sigal and Ethier, 2009; Tektas and Lutjen-Drecoll, 2009; Vranka et al, 2015). For example, patients with glaucoma often have changes in the architecture of the LC seen as a posterior displacement of the LC or “cupping” that is due to changes in the mechanical properties of the ECM (Downs, 2015; Roberts et al, 2010; Yang et al, 2011).…”

The lysophosphatidic acid axis in fibrosis: Implications for glaucoma

“…The TM and the LC are biochemically comparable tissues, with similar cellular properties and gene expression. 28,29 The alterations in ECM gene expression observed in the TM in primary open angle glaucoma (POAG) resemble those observed in the LC, therefore, it is hypothesized that the fibrotic changes affecting both of these regions in glaucoma may result from a common defect. 28 Furthermore, simulation of raised IOP with mechanical stretch leads to similar F I G U R E 1 Anatomy of the eye and aqueous humour circulation system: The eye is composed of an anterior chamber and a posterior chamber.…”

“…In glaucoma there is fibrosis in the lamina cribrosa which contributes to visual loss through retinal ganglion cell axonal degeneration upregulation of TGF-β1, α-SMA and collagen types I and IV in both regions. 28 Human TM cells bear similarities to myofibroblasts, as well as possessing endothelial cell-like characteristics. 30 A recent publication on single cell transcriptomics in the TM described both fibroblastlike and myofibroblast-like types of TM cells.…”