Localization and developmental expression patterns of CSPG-cs56 (aggrecan) in normal and dystrophic retinas in two rat strains

Chen, Lifeng; FitzGibbon, Thomas; He, Jianjun; Yin, Zheng

doi:10.1016/j.expneurol.2012.01.023

Cited by 10 publications

(10 citation statements)

References 77 publications

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“…Aggrecan expression was previously investigated in a dystrophic rat model68. Here, no retinal dysregulation was found in comparison to non-dystrophic rats.…”

Section: Discussionmentioning

confidence: 67%

Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

Reinhard

Renner

Wiemann

et al. 2017

Sci Rep

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Retinal ischemia occurs in a variety of eye diseases. Restrained blood flow induces retinal damage, which leads to progressive optic nerve degeneration and vision loss. Previous studies indicate that extracellular matrix (ECM) constituents play an important role in complex tissues, such as retina and optic nerve. They have great impact on de- and regeneration processes and represent major candidates of central nervous system glial scar formation. Nevertheless, the importance of the ECM during ischemic retina and optic nerve neurodegeneration is not fully understood yet. In this study, we analyzed remodeling of the extracellular glycoproteins fibronectin, laminin, tenascin-C and tenascin-R and the chondroitin sulfate proteoglycans (CSPGs) aggrecan, brevican and phosphacan/RPTPβ/ζ in retinae and optic nerves of an ischemia/reperfusion rat model via quantitative real-time PCR, immunohistochemistry and Western blot. A variety of ECM constituents were dysregulated in the retina and optic nerve after ischemia. Regarding fibronectin, significantly elevated mRNA and protein levels were observed in the retina following ischemia, while laminin and tenascin-C showed enhanced immunoreactivity in the optic nerve after ischemia. Interestingly, CSPGs displayed significantly increased expression levels in the optic nerve. Our study demonstrates a dynamic expression of ECM molecules following retinal ischemia, which strengthens their regulatory role during neurodegeneration.

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“…Aggrecan expression was previously investigated in a dystrophic rat model68. Here, no retinal dysregulation was found in comparison to non-dystrophic rats.…”

Section: Discussionmentioning

confidence: 67%

Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

Reinhard

Renner

Wiemann

et al. 2017

Sci Rep

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“…We also examined the involvement of CSPG, a potent inhibitor of cell survival and migration that is normally expressed in the interphotoreceptor matrix [31, 35, 36]. When chondroitinase ABC was administered into the subretinal space of Rho -/- mice simultaneously with a transplant, retinal migration was facilitated by breakdown of the glial scar and CSPGs [37].…”

Section: Resultsmentioning

confidence: 99%

Neonatal disease environment limits the efficacy of retinal transplantation in the LCA8 mouse model

et al. 2016

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BackgroundMutations of Crb1 gene cause irreversible and incurable visual impairment in humans. This study aims to use an LCA8-like mouse model to identify host-mediated responses that might interfere with survival, retinal integration and differentiation of grafted cells during neonatal cell therapy.MethodsMixed retinal donor cells (1 ~ 2 × 104) isolated from neural retinas of neonatal eGFP transgenic mice were injected into the subretinal space of LCA8-like model neonatal mice. Markers of specific cell types were used to analyze microglial attraction, CSPG induction and retinal cell differentiation. The positions of host retinal cells were traced according to their laminar location during disease progression to look for host cell rearrangements that might inhibit retinal integration of the transplanted cells.ResultsTransplanted retinal cells showed poor survival and attracted microglial cells, but CSPG was not greatly induced. Retinas of the LCA8 model hosts underwent significant cellular rearrangement, including rosette formation and apical displacement of inner retinal cells.ConclusionsLocal disease environment, particularly host immune responses to injected cells and formation of a physical barrier caused by apical migration of host retinal cells upon disruption of outer limiting membrane, may impose two major barriers in LCAs cell transplantation therapy.

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“…Using the broad-spectrum CSPG antibody CS-56 we have seen very different patterns of expression in different models of degeneration (Barber et al, 2013). A recent study showed the CSPG, aggrecan, to be markedly upregulated in two rat models of retinal dystrophy (Chen et al, 2012), while microarray analysis of individual Muller glial cells from a mouse model of RP identified a significant increase in CSPG5 (neuroglycan) (Roesch et al, 2012). ChABC, a broad-spectrum chondroitinase that can break down a number of CSPGs has been used with good effect in promoting axonal regrowth in the damaged spinal cord.…”

Section: Critique and Discussionmentioning

confidence: 99%

Advances in repairing the degenerate retina by rod photoreceptor transplantation

Pearson¹

2014

Biotechnology Advances

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Despite very different aetiologies, age-related macular degeneration (AMD) and most inherited retinal disorders culminate in the same final common pathway, loss of the light-sensitive photoreceptors. There are few clinical treatments and none can reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. The past decade has seen a number of landmark achievements in this field, which together provide strong justification for continuing investigation into photoreceptor replacement strategies. These include proof of principle for restoring vision by rod-photoreceptor transplantation in mice with congenital stationary night blindness and advances in stem cell biology, which have led to the generation of complete optic structures in vitro from embryonic stem cells. The latter represents enormous potential for generating suitable and renewable donor cells with which to achieve the former. However, there are still challenges presented by the degenerating recipient retinal environment that must be addressed as we move to translating these technologies towards clinical application.

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Localization and developmental expression patterns of CSPG-cs56 (aggrecan) in normal and dystrophic retinas in two rat strains

Cited by 10 publications

References 77 publications

Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

Neonatal disease environment limits the efficacy of retinal transplantation in the LCA8 mouse model

Advances in repairing the degenerate retina by rod photoreceptor transplantation

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