Lens epithelial cells promote regrowth of retinal ganglion cells in culture and in vivo

Wong, Wai Kai; Cheung, A. W. S.; Cho, Eric

doi:10.1097/01.wnr.0000215776.91850.96

Cited by 5 publications

(4 citation statements)

References 25 publications

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“…A great deal of work has studied RGCs with or without various additives to encourage neurite outgrowth or to neutralize inhibitory signals. [74][75][76][77][78] Another study which also utilized the zebrafish ONX model profiled gene expression patterns in isolated RGCs at 3 days post-ONX. 29 Results of this study provide a valuable comparison with our dataset (Table S3) as together they can help differentiate the transcriptional response of RGCs from that of other cell types in the eye during regeneration.…”

Section: Journal Of Experimental Neuroscience 2010:4 Common Factors Imentioning

confidence: 99%

Time course Analysis of Gene expression patterns in ZebrafIsh Eye during Optic Nerve Regeneration

McCurley

Callard

2010

J Exp Neurosci

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It is well-established that neurons in the adult mammalian central nervous system (CNS) are terminally differentiated and, if injured, will be unable to regenerate their connections. In contrast to mammals, zebrafish and other teleosts display a robust neuroregenerative response. Following optic nerve crush (ONX), retinal ganglion cells (RGC) regrow their axons to synapse with topographically correct targets in the optic tectum, such that vision is restored in ∼21 days. What accounts for these differences between teleostean and mammalian responses to neural injury is not fully understood. A time course analysis of global gene expression patterns in the zebrafish eye after ONX can help to elucidate cellular and molecular mechanisms that contribute to a successful neuroregeneration. To define different phases of regeneration after ONX, alpha tubulin 1 (tuba1) and growth-associated protein 43 (gap43), markers previously shown to correspond to morphophological events, were measured by real time quantitative PCR (qPCR). Microarray analysis was then performed at defined intervals (6 hours, 1, 4, 12, and 21 days) post-ONX and compared to SHAM. Results show that optic nerve damage induces multiple, phase-related transcriptional programs, with the maximum number of genes changed and highest fold-change occurring at 4 days. Several functional groups affected by optic nerve regeneration, including cell adhesion, apoptosis, cell cycle, energy metabolism, ion channel activity, and calcium signaling, were identified. Utilizing the whole eye allowed us to identify signaling contributions from the vitreous, immune and glial cells as well as the neural cells of the retina. Comparisons between our dataset and transcriptional profiles from other models of regeneration in zebrafish retina, heart and fin revealed a subset of commonly regulated transcripts, indicating shared mechanisms in different regenerating tissues. Knowledge of gene expression patterns in all components of the eye in a model of successful regeneration provides an entry point for functional analyses, and will help in devising hypotheses for testing normal and toxic regulatory factors.

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Section: Journal Of Experimental Neuroscience 2010:4 Common Factors Imentioning

confidence: 99%

Time course Analysis of Gene expression patterns in ZebrafIsh Eye during Optic Nerve Regeneration

McCurley

Callard

2010

J Exp Neurosci

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“…To date, the most significant non-structural role for βB2-crystallin elucidated has been in promoting axonal regeneration in the retina. It has been long established that lens injury mitigates retinal ganglion cell loss and promotes retinal ganglion cell axon regeneration (Fischer et al, 2001; Fischer et al, 2000; Stupp et al, 2005; Wang et al, 2009b; Wong et al, 2006). As a substantial component of lens cells, crystallins were attractive candidates as the driving force underlying the protective effects of lens injury.…”

mentioning

confidence: 99%

BetaB2-crystallin mutations associated with cataract and glaucoma leads to mitochondrial alterations in lens epithelial cells and retinal neurons

Dulle

Rübsam

Garnai

et al. 2017

Experimental Eye Research

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Crystallin proteins are the most prominent protein of the lens and have been increasingly shown to play critical roles in other tissues, especially the retina. Members of all 3 sub-families of crystallins, alpha-, beta- and gamma-crystallins have been reported in the retina during diabetes, traumatic injury and other retinal diseases. While their specific role in the retina is still unclear and may vary, beta-crystallin proteins have been shown to play a critical role in ganglion cell survival following trauma. We recently reported the correlation between a gene conversion in the betaB2-crystallin gene and a phenotype of familial congenital cataract. Interestingly, in half of the patients, this phenotype was associated with glaucoma. Taken together, these data suggested that the mutations we recently reported could have an impact on the role of betaB2-crystallin in both lens epithelial cells and retinal neurons. Consistent with this hypothesis, we show in the current study that the gene conversion leading to an amino acid conversion lead to a loss of solubility and a change of subcellular localization of betaB2-crystallin in both cell types. While the overall observations were similar in both cell types, there were some important nuances between them, suggesting different roles and regulation of betaB2-crystallin in lens cells versus retinal neurons. The data reported in this study strongly support a significant role of betaB2-crystallin in both lenticular and retinal ocular tissues and warrant further analysis of its regulation and its impact not only in cataract formation but also in retinal neurodegenerative diseases.

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“…One of the advantages of this culture system is its ability to be replicated in other species including the human and the monkey retina (Thanos and Thiel 1990;Rose et al 2008). A second advantage is that purified neurotrophic factors can be tested Thanos et al 1993;Fischer et al 2000Fischer et al , 2008Böcker-Meffert et al 2002;Stupp et al 2005;Wong et al 2006). A third advantage is that retinal tissue from subjects with defined diseases such as diabetes (Takano et al 1999) and glaucoma (Lasseck et al 2007) can be used for examining their effects on axonal regeneration.…”

Section: Growth Factors Required In Vitromentioning

confidence: 99%

Traumatology of the optic nerve and contribution of crystallins to axonal regeneration

et al. 2012

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Within a few decades, the repair of long neuronal pathways such as spinal cord tracts, the optic nerve or intracerebral tracts has gone from being strongly contested to being recognized as a potential clinical challenge. Cut axonal stumps within the optic nerve were originally thought to retract and become irreversibly necrotic within the injury zone. Optic nerve astrocytes were assumed to form a gliotic scar and remodelling of the extracellular matrix to result in a forbidden environment for re-growth of axons. Retrograde signals to the ganglion cell bodies were considered to prevent anabolism, thus also initiating apoptotic death and gliotic repair within the retina. However, increasing evidence suggests the reversibility of these regressive processes, as shown by the analysis of molecular events at the site of injury and within ganglion cells. We review optic nerve repair from the perspective of the proximal axon stump being a major player in determining the successful formation of a growth cone. The axonal stump and consequently the prospective growth cone, communicates with astrocytes, microglial cells and the extracellular matrix via a panoply of molecular tools. We initially highlight these aspects on the basis of recent data from numerous laboratories. Then, we examine the mechanisms by which an injury-induced growth cone can sense its surroundings within the area distal to the injury. Based on requirements for successful axonal elongation within the optic nerve, we explore the models employed to instigate successful growth cone formation by ganglion cell stimulation and optic nerve remodelling, which in turn accelerate growth. Ultimately, with regard to the proteomics of regenerating retinal tissue, we discuss the discovery of isoforms of crystallins, with crystallin beta-b2 (crybb2) being clearly upregulated in the regenerating retina. Crystallins are produced and used to promote the elongation of growth cones. In vivo and in vitro, crystallins beta and gamma additionally promote the growth of axons by enhancing the production of ciliary neurotrophic factor (CNTF), indicating that they also act on astrocytes to promote axonal regrowth synergistically. These are the first data showing that axonal regeneration is related to crybb2 movement within neurons and to additional stimulation of CNTF. We demonstrate that neuronal crystallins constitute a novel class of neurite-promoting factors that probably operate through an autocrine and paracrine mechanism and that they can be used in neurodegenerative diseases. Thus, the post-injury fate of neurons cannot be seen merely as inevitable but, instead, must be regarded as a challenge to shape conditions for initiating growth cone formation to repair the damaged optic nerve.

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Lens epithelial cells promote regrowth of retinal ganglion cells in culture and in vivo

Cited by 5 publications

References 25 publications

Time course Analysis of Gene expression patterns in ZebrafIsh Eye during Optic Nerve Regeneration

Time course Analysis of Gene expression patterns in ZebrafIsh Eye during Optic Nerve Regeneration

BetaB2-crystallin mutations associated with cataract and glaucoma leads to mitochondrial alterations in lens epithelial cells and retinal neurons

Traumatology of the optic nerve and contribution of crystallins to axonal regeneration

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