Differential expression of receptor protein tyrosine phosphatases accompanies the reorganisation of the retina upon laser lesion

Abstract

The regulation of protein phosphorylation plays an essential role in virtually all aspects of eukaryotic development. Beginning with the regulation of the cell cycle to cellular proliferation and differentiation, the delicate balance between the phosphorylating activity of kinases and the dephosphorylation by phosphatases controls the outcome of many signal transduction cascades. The generation of cellular diversity occurs in an environment that is structured by the extracellular matrix (ECM) which forms a surrounding niche for stem and progenitor cells. Cell-cell and cell-matrix interactions elicit specific signaling pathways that control cellular behavior. In pathological situations such as neural degenerating diseases, gene expression patterns and finally the composition of the ECM change dramatically. This leads to changes of cell behavior and finally results in the failure of regeneration and functional restoration in the adult central nervous system. In order to study the roles of tyrosine phosphatases and ECM in this context, we analyzed the effects of laser-induced retinal injury on the regulation of the receptor protein tyrosine phosphatases (RPTP) RPTPBr7, Phogrin and RPTPbeta/zeta. The latter occurs in several isoforms, including the soluble released chondroitin sulfate proteoglycan phosphacan that is expressed in the developing retina. The receptor variants RPTPbeta/zeta(long) and RPTPbeta/zeta(short) may serve as receptors of tenascin-proteins and serve as modulators of cell intrinsic signaling in response to the ECM. Using quantitative real-time RT-PCR analysis, we show here a time-dependent pattern of gene expression of these molecules following laser lesions of the retina.

Early remodelling of the extracellular matrix proteins tenascin‐C and phosphacan in retina and optic nerve of an experimental autoimmune glaucoma model

“…In the adult retina, tenascin-C is expressed by amacrine and displaced amacrine cells as well as by horizontal cells [64]. In central nervous tissue a dynamic regulation of tenascin-C was additionally described in reactive astrocytes after lesions [65][66][67][68]. Based on these findings, we speculate that reactive astrocytes of the optic nerve and neuronal cells of the retina up-regulate tenascin-C following RGC death and axon degeneration.…”

“…Another CSPG, neurocan, was found to be up‐regulated in the retina after transient ischaemia . Moreover, in a retinal laser lesion model phosphacan/RPTP β / ζ exhibits increased expression levels . It was shown that it promotes axonal regeneration and repair processes in the CNS .…”

Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

“…Other extracellular interaction partners are TN-C, Contactin/F3/F11, the cell adhesion molecules L1CAM and NCAM (Klausmeyer et al, 2007), and FGF (Milev et al, 1998b). RPTPβ isoforms are regulated after knife lesion of the cerebral cortex (Dobbertin et al, 2003), striatal stab wound (Barker et al, 1996), and after retinal laser lesion (Besser et al, 2009) and are critical for recovery (Harroch et al, 2002). PSI as the smallest member of the RPTPβ family promotes axon growth (Garwood et al, 2003).…”

Tenascins in Retinal and Optic Nerve Neurodegeneration

“…Notably, elevated levels of the CSPGs aggrecan, brevican and phosphacan were noted in the optic nerve after retinal ischemia (Reinhard et al, 2017 ). Following laser lesion, differential expression of RPTPβ/ζ was observed in the retina (Besser et al, 2009 ). In the non-injured retina of Tnc deficient mice, an upregulation of the DSD-1 epitope, recognized by the monoclonal antibody 473HD and localized on phosphacan/RPTPβ/ζ, was revealed when compared to the wild-type mice (Besser et al, 2012 ).…”