Retinal Cell Responses to Elevated Intraocular Pressure: A Gene Array Comparison between the Whole Retina and Retinal Ganglion Cell Layer

Abstract

Isolation of RGCL by LCM allows a more refined detection of gene response to elevated pressure and improves the potential of determining cellular mechanisms in RGCs and their supporting cells that could be targets for enhancing RGC survival.

Differential Gene Expression in Glaucoma

“…Both ocular hypertension and optic nerve transection lead to upregulation of immediate early response genes. C-Jun, Junb, and Atf3 (activating transcription factor 3) were up-regulated in both models (Yang et al 2007;Guo et al 2010). These factors are downstream from JNK, and the phosphorylated, active form of JNK is present at increased levels in glaucoma Levkovitch-Verbin et al 2007).…”

“…These mice develop an increase in IOP at 6 mo of age, followed by a sectorial degeneration of retinal ganglion cells (Danias et al 2003;Jakobs et al 2005;Libby et al 2005;Schlamp et al 2006). Among the studies that used an ocular hypertension model, some have assayed differential gene expression in the whole retina (Miyahara et al 2003;Ahmed et al 2004;Walsh et al 2009), and others have analyzed cells isolated from the ganglion cell layer by laser capture microdissection (Guo et al 2010Wang et al 2010). For microarray analysis in the inherited glaucoma models in mice (DBA/2J) and rats (RCS-rdy 2 ), whole retinas were used (Naskar and Thanos 2006;Steele et al 2006;Panagis et al 2010Panagis et al , 2011Howell et al 2011).…”

“…One of them is the prominent up-regulation of genes involved in the inflammatory and immune response. For instance, several studies reported up-regulation of lipocalin 2, both after an increase of IOP and in DBA/2J mice (Ahmed et al 2004;Steele et al 2006;Yang et al 2007;Guo et al 2010Guo et al , 2011Howell et al 2011). Lipocalin 2 is a general marker of tissue response to injury and is up-regulated among others by IL1b, IL17, and TNFa (Li and Chan 2011).…”

“…It has also emerged as a marker of astrocyte reactivity in the brain (Zamanian et al 2012). Other immune response genes found to be up-regulated in glaucoma models include a-2-macroglobulin, MHC class II RT1.u-D-a chain, Interferon-induced transmembrane protein 1 (Ifitm3/Fgls), and Chemokine (C-C motif ) ligand 12 (Ahmed et al 2004;Steele et al 2006;Guo et al 2010). Of particular interest among the immune response genes are members of the complement cascade.…”

Anatomical and Molecular Responses Triggered in the Retina by Axonal Injury

“…These genes are mainly related to inflammation, apoptosis, cytoskeleton and extracellular matrix remodeling. Guo et al, (2010) analyzed the gene expression patterns occurring in the retina in response to elevated IOP induced by hypertonic saline injection. Their big contribution has been that the analysis was performed in extracts from whole retinas and in extracts from cells isolated from the ganglion cell layer.…”