Identification of Gene Expression Changes Associated with the Progression of Retinal Degeneration in the<i>rd1</i>Mouse

Hackam, Abigail S.; Strom, R.; Liu, Dongmei; Jiang, Qian; Wang, Chenwei; Otteson, Deborah C.; Gunatilaka, Tushara L.; Farkas, Ronald H.; Chowers, Itay; Kageyama, Masaaki; Léveillard, Thierry; Sahel, José‐Alain; Campochiaro, Peter A.; Parmigiani, Giovanni; Zack, Donald J.

doi:10.1167/iovs.03-1184

Cited by 82 publications

(71 citation statements)

References 75 publications

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“…Compared to the total number of genes with preferential expression, we found higher frequencies of proliferation and cell death genes expressed in the brain than retina, and nucleic acid processing genes in retina than brain. Among the transcripts preferentially expressed in the brain were many known and unknown genes not previously reported to have a preferential expression pattern in different regions of the brain [5,29]. We demonstrated also that expression patterns are quite restricted to individual cortex areas, as few differential expressed genes showed overlap between the examined brain regions (Figure 2).…”

Section: Discussionsupporting

confidence: 62%

“…Insights into these mechanisms are critical to develop therapeutic strategies, and these studies are dependent on animal models. One approach to examine the pathways involved in retinal degenerative diseases in animal models is gene expression profile analysis with the aim of identifying early alterations in gene expression that contribute to photoreceptor cell death [5]. The microarray technology shows potential as a useful tool to identify genes and gene pathways involved in ocular disease progression and may therefore aid in the characterization and classification of these diseases, possibly identifying a common mechanism linking disorders into groups [6,7].…”

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confidence: 99%

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Characterization of Gene Expression Profiles of Normal Canine Retina and Brain Using a Retinal cDNA Microarray

Pàez

Zangerl

Sellers

et al. 2008

Advances in Experimental Medicine and Biology

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Section: Discussionsupporting

confidence: 62%

mentioning

confidence: 99%

Characterization of Gene Expression Profiles of Normal Canine Retina and Brain Using a Retinal cDNA Microarray

Pàez

Zangerl

Sellers

et al. 2008

Advances in Experimental Medicine and Biology

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“…Interestingly, Dkk3 expression also had a significant prosurvival effect on HEK293 cells exposed to H 2 O 2 -induced oxidative stress (64) and to chemotherapeutic agents (65). As discussed earlier, Wnt signaling is generally anti-apoptotic.…”

Section: What Are the Consequences Of Wnt-related Expression Changes?mentioning

confidence: 71%

The Wnt Signaling Pathway in Retinal Degenerations

Hackam

2005

IUBMB Life (International Union of Biochemistry and Molecular B

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The retina is a complex tissue composed of multiple interconnected cell layers, highly specialized for transforming light and color into electrical signals perceived by the brain. Damage or death of the primary light‐sensing cells, the photoreceptors, results in devastating effects on vision. Despite the identification of numerous mutations that cause inherited retinal degenerations, the cellular and molecular mechanisms leading from the primary mutations to photoreceptor apoptosis are not understood. Wnt signaling has essential regulatory functions in a wide variety of critical developmental processes. Our research and others' have suggested that the Wnt pathway may be involved in retinal degeneration. Wnt ligands regulate developmental death of Drosophila photoreceptors, dysregulated Wnt signaling is involved in neuronal degeneration elsewhere in the central nervous system and Wnts control the expression of pro‐survival growth factors in mammalian tissues. Additionally, altered expression of Wnt pathway genes, including the anti‐apoptotic Wnt signaling regulator Dickkopf 3 (Dkk3), were observed during photoreceptor loss. This review examines the evidence and develops a model proposing a pro‐survival role for Wnt signaling during photoreceptor injury. Because manipulating Wnt signaling has been demonstrated to have therapeutic potential for the treatment of Alzheimers disease, understanding the involvement of Wnts in photoreceptor death will determine whether targeting the Wnt pathway should also be considered as a possible therapeutic strategy for retinal degenerations. IUBMB Life, 57: 381‐388, 2005

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“…Elevated levels of SFRP1 have also been reported in the retinas of patients affected by retinitis pigmentosa, an inherited disease characterised by the progressive loss of photoreceptors (Hackam, 2005;Hackam et al, 2004). Although SFRP1 maps close to a locus associated with an uncharacterised form of retinitis pigmentosa, no mutations have been found in a cohort of screened patients (GarciaHoyos et al, 2004).…”

Section: The Roles Of Sfrps In Pathological Eventsmentioning

confidence: 99%

“…Interestingly, a decrease in the activity of other Wnt inhibitors, such as Dickkopf-1 or sclerostin, is also associated with an increase in bone-mass formation, whereas loss-of-function mutations in LRP5 cause osteoporosis, suggesting an important general role of Wnt signalling in bone formation (Baron and Rawadi, 2007). A possible molecular basis for this function of Wnt was suggested by the recent demonstration that Wnt signalling through GSK3 activation enhances BMP signalling, which potently induces bone morphogenesis (Fuentealba et al, 2007).Elevated levels of SFRP1 have also been reported in the retinas of patients affected by retinitis pigmentosa, an inherited disease characterised by the progressive loss of photoreceptors (Hackam, 2005;Hackam et al, 2004). Although SFRP1 maps close to a locus associated with an uncharacterised form of retinitis pigmentosa, no mutations have been found in a cohort of screened patients (GarciaHoyos et al, 2004).…”

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confidence: 99%

Beyond Wnt inhibition: new functions of secreted Frizzled-related proteins in development and disease

Bovolenta

Esteve

Ruiz

et al. 2008

Journal of Cell Science

545

523

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types of cancers, bone pathologies, retinal degeneration and hypophosphatemic diseases, indicating that their activity is fundamental for tissue homeostasis. Here we review some of the debated aspects of SFRP-Wnt interactions and discuss the new and emerging roles of SFRPs. Journal of Cell Science 738 were isolated either through sequence homology with Fz receptors (Rattner et al., 1997) or, independently of Wnt activity, through their involvement in apoptosis (Melkonyan et al., 1997), or their co-purification with the heparin-binding factor hepatocyte growth factor/scattered factor (Finch et al., 1997).Since their discovery, interest in this family of molecules has grown progressively, particularly because recent observations have offered a new perspective on their functions and mechanisms of action in both development and disease. These studies indicate that SFRPs are not merely Wnt-binding proteins but can also antagonise one another's activity (Yoshino et al., 2001), bind to Fz receptors (Bafico et al., 1999;Rodriguez et al., 2005) and provide axon-guidance information (Rodriguez et al., 2005). Moreover, they can interact with other receptors or matrix molecules (Chuman et al., 2004;Hausler et al., 2004; and interfere with BMP signalling (Lee, H. et al., 2006;Muraoka et al., 2006;Yabe et al., 2003) by acting as proteinase inhibitors (Lee, H. et al., 2006). Furthermore, their expression is altered in different types of cancers (Rubin et al., 2006), in bone pathologies , retinal degeneration (Jones et al., 2000) and hypophosphatemic diseases (Berndt and Kumar, 2007), which indicates that their activity is fundamental for tissue homeostasis. Reviews that centre on Wnt antagonism by SFRPs have recently been published elsewhere (Cadigan and Liu, 2006;Jones and Jomary, 2002;Kawano and Kypta, 2003); here, we discuss new aspects of SFRP activity, and review SFRP structure, expression and interactions with Wnt proteins. The family of SFRPsThe SFRP family comprises five members in humans, SFRP1 to SFRP5, in which SFRP3 is the orthologue of the founding member Frzb. Sequence comparison and phylogenetic analysis show that SFRP1, SFRP2 and SFRP5 are closely related, and cluster together in a subgroup that diverges from the one formed by the related SFRP3 and SFRP4 (Fig. 1). This clustering also reflects a different genomic organisation. SFRP1, SFRP2 and SFRP5 are encoded by three exons on chromosome 8p12-p11.1, 4q31.3 and 10q24.1, respectively (Garcia-Hoyos et al., 2004), whereas SFRP3 and SFRP4 are both encoded by six exons -on chromosome 2q31-q33 and 7p14-p13, respectively. Orthologues of the five human genes have been found in all vertebrate species analysed so far ( Fig. 1). Notably, a third subgroup, apparently not present in mammals, has been identified in Xenopus, zebrafish and chick. The components of this subgroup, named Sizzled, Crescent and Tlc, share sequence similarities with the SFRP1-SFRP2-SFRP5 subgroup (Fig. 1), and are characterised by a very restricted and anterior expression in gastrulating embryos (B...

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Identification of Gene Expression Changes Associated with the Progression of Retinal Degeneration in therd1Mouse

Cited by 82 publications

References 75 publications

Characterization of Gene Expression Profiles of Normal Canine Retina and Brain Using a Retinal cDNA Microarray

Characterization of Gene Expression Profiles of Normal Canine Retina and Brain Using a Retinal cDNA Microarray

The Wnt Signaling Pathway in Retinal Degenerations

Beyond Wnt inhibition: new functions of secreted Frizzled-related proteins in development and disease

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