Abstract
Purpose: :
Among the most upregulated genes in our microarray analysis of rat glaucoma model optic nerve heads (ONH) is periostin (Postn), a matricellular protein linking the extracellular matrix to cell surface receptors. Postn expression increases collagen fibril diameter and cross linking, resulting in added tissue tensile strength and stiffness (decreased compliance). In cardiovascular injury, Postn is associated with stem cell recruitment and differentiation to fibroblasts. Because altered tissue mechanical properties and cell proliferation are characteristics of early glaucomatous ONH injury, we further examined Postn expression and localization.
Methods: :
Unilateral IOP elevation was produced in rats by episcleral vein injection of hypertonic saline. ONH mRNA was extracted and amplified for microarray (N=27) and qPCR analysis (N=56) or globes sectioned for immunohistochemistry (N=20). Retrobulbar optic nerve sections were graded for axon loss. Fellow, early injury (<15% axon loss) and advanced injury (>15% loss) groups were compared using Significance Analysis of Microarrays and ANOVA. Postn changes were correlated with axon loss by regression analysis.
Results: :
By microarray, Postn expression was increased to 520% in early injury and 1610% in advanced injury. qPCR demonstrated a significant positive correlation between Postn level and nerve injury (r2=0.24, p<0.0001), maximizing at 2703±862% in ONH with >40% axon loss. Postn immunolocalization to ONH blood vessels was highly correlated to increasing nerve injury (r2=0.86, p<0.0001, Figure).
Conclusions: :
The dramatic upregulation of Postn and its localization to glaucoma model ONH blood vessels suggests a potential vascular contribution to the altered cellular and mechanical properties of the glaucomatous ONH.
Keywords: optic nerve • extracellular matrix • blood supply