Gene Expression Signatures in Tree Shrew Sclera in Response to Three Myopiagenic Conditions

Guo, Lin; Frost, Michael R.; He, Li; Siegwart, John T.; Norton, Thomas T.

doi:10.1167/iovs.13-12551

Cited by 58 publications

(63 citation statements)

References 79 publications

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“…32 Downregulation of Col12a1 reported in our qRT-PCR data in both PPZ FD versus PPZ fellow eye and PPZ FD versus peripheral temporal FD fellow eye experiments is consistent with the above studies on matrix degradation observed during myopia. In the case of Timp3, upregulation was observed in both PPZ FD versus PPZ fellow eye and PPZ FD versus peripheral temporal FD fellow eye experiments, which is contrary to findings previously reported.…”

Section: Discussionsupporting

confidence: 92%

Gene Expression and Pathways Underlying Form Deprivation Myopia in the Guinea Pig Sclera

Srinivasalu

McFadden

Medcalf

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionsupporting

confidence: 92%

Gene Expression and Pathways Underlying Form Deprivation Myopia in the Guinea Pig Sclera

Srinivasalu

McFadden

Medcalf

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…In response to myopiagenic visual stimuli, the retinal compartment of the direct emmetropization pathway generates GO signals that are conveyed into the RPE (He, Frost, & Norton, 2014), thence into the choroid (He et al, 2014), and eventually reach the sclera (Guo et al, 2013) where they modulate the axial elongation rate of the growing postnatal eye (Siegwart & Norton, 1998). It seems evident that the three GO conditions used in this study, minus lens wear, form deprivation, and continuous darkness, must produce dramatically different responses in many of the retinal horizontal, bipolar, and amacrine cells and in the patterns of retinal ganglion cell activity that are sent through the optic nerve to central visual structures, yet all three produce a nearly identical response in the scleral fibroblasts (Guo et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have suggested that the retinal emmetropization-related signaling produced by these two GO conditions can be distinguished (Bartmann et al, 1994; Bitzer, Feldkaemper, & Schaeffel, 2000; Fujikado et al, 1997; Kee, Marzani, & Wallman, 2001; Schaeffel et al, 1994; Wildsoet, 2003; Yew & Wildsoet, 2003). However, in the sclera, it has been found that ML and FD produce nearly identical gene expression signatures; DK treatment also produces a similar gene expression signature (Guo et al, 2013). It appears that the different retinal activity produced by these three myopiagenic conditions may be converted into a common set of emmetropization signals as it passes through the direct RPE-choroid-sclera emmetropization pathway.…”

Section: Introductionmentioning

confidence: 99%

Gene expression signatures in tree shrew choroid in response to three myopiagenic conditions

Frost

Siegwart

et al. 2014

Vision Research

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We examined gene expression in tree shrew choroid in response to three different myopiagenic conditions: minus lens (ML) wear, form deprivation (FD), and continuous darkness (DK). Four groups of tree shrews (n = 7 per group) were used. Starting 24 days after normal eye opening (days of visual experience [DVE]), the ML group wore a monocular −5 D lens for 2 days. The FD group wore a monocular translucent diffuser for 2 days. The DK group experienced continuous darkness binocularly for 11 days, starting at 17 DVE. An age-matched normal group was examined at 26 DVE. Quantitative PCR was used to measure the relative (treated eye vs. control eye) differences in mRNA levels in the choroid for 77 candidate genes. Small myopic changes were observed in the treated eyes (relative to the control eyes) of the ML group (−1.0 ± 0.2 D; mean ± SEM) and FD group (−1.9 ± 0.2 D). A larger myopia developed in the DK group (−4.4 ± 1.0 D) relative to Normal eyes (both groups, mean of right and left eyes). In the ML group, 28 genes showed significant differential mRNA expression; eighteen were down-regulated. A very similar pattern occurred in the FD group; twenty-seven of the same genes were similarly regulated, along with five additional genes. Fewer expression differences in the DK group were significant compared to normal or the control eyes of the ML and FD groups, but the pattern was similar to that of the ML and FD differential expression patterns. These data suggest that, at the level of the choroid, the gene expression signatures produced by “GO” emmetropization signals are highly similar despite the different visual conditions.

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“…The tree shrew is a small animal (a prosimian primate) indigenous to southwest Asia and has been used to study myopia and depression (21)(22)(23)(24). The recently published complete genome and transcriptome of the tree shrew suggest that it is closely related to primates (25,26).…”

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confidence: 99%

Herpes Simplex Virus 1 Infection of Tree Shrews Differs from That of Mice in the Severity of Acute Infection and Viral Transcription in the Peripheral Nervous System

Wang

et al. 2016

J Virol

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Studies of herpes simplex virus (HSV) infections of humans are limited by the use of rodent models such as mice, rabbits, and guinea pigs. Tree shrews (Tupaia belangeri chinensis) are small mammals indigenous to southwest Asia. At behavioral, anatomical, genomic, and evolutionary levels, tree shrews are much closer to primates than rodents are, and tree shrews are susceptible to HSV infection. Thus, we have studied herpes simplex virus 1 (HSV-1) infection in the tree shrew trigeminal ganglion (TG) following ocular inoculation. In situ hybridization, PCR, and quantitative reverse transcription-PCR (qRT-PCR) analyses confirm that HSV-1 latently infects neurons of the TG. When explant cocultivation of trigeminal ganglia was performed, the virus was recovered after 5 days of cocultivation with high efficiency. Swabbing the corneas of latently infected tree shrews revealed that tree shrews shed virus spontaneously at low frequencies. However, tree shrews differ significantly from mice in the expression of key HSV-1 genes, including ICP0, ICP4, and latency-associated transcript (LAT). In acutely infected tree shrew TGs, no level of ICP4 was observed, suggesting the absence of infection or a very weak, acute infection compared to that of the mouse. Immunofluorescence staining with ICP4 monoclonal antibody, and immunohistochemistry detection by HSV-1 polyclonal antibodies, showed a lack of viral proteins in tree shrew TGs during both acute and latent phases of infection. Cultivation of supernatant from homogenized, acutely infected TGs with RS1 cells also exhibited an absence of infectious HSV-1 from tree shrew TGs. We conclude that the tree shrew has an undetectable, or a much weaker, acute infection in the TGs. Interestingly, compared to mice, tree shrew TGs express high levels of ICP0 transcript in addition to LAT during latency. However, the ICP0 transcript remained nuclear, and no ICP0 protein could be seen during the course of mouse and tree shrew TG infections. Taken together, these observations suggest that the tree shrew TG infection differs significantly from the existing rodent models. IMPORTANCEHerpes simplex viruses (HSVs) establish lifelong infection in more than 80% of the human population, and their reactivation leads to oral and genital herpes. Currently, rodent models are the preferred models for latency studies. Rodents are distant from primates and may not fully represent human latency. The tree shrew is a small mammal, a prosimian primate, indigenous to southwest Asia. In an attempt to further develop the tree shrew as a useful model to study herpesvirus infection, we studied the establishment of latency and reactivation of HSV-1 in tree shrews following ocular inoculation. We found that the latent virus, which resides in the sensory neurons of the trigeminal ganglion, could be stress reactivated to produce infectious virus, following explant cocultivation and that spontaneous reactivation could be detected by cell culture of tears. Interestingly, the tree shrew model is quite different from...

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Gene Expression Signatures in Tree Shrew Sclera in Response to Three Myopiagenic Conditions

Cited by 58 publications

References 79 publications

Gene Expression and Pathways Underlying Form Deprivation Myopia in the Guinea Pig Sclera

Gene Expression and Pathways Underlying Form Deprivation Myopia in the Guinea Pig Sclera

Gene expression signatures in tree shrew choroid in response to three myopiagenic conditions

Herpes Simplex Virus 1 Infection of Tree Shrews Differs from That of Mice in the Severity of Acute Infection and Viral Transcription in the Peripheral Nervous System

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