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

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

doi:10.1016/j.visres.2014.07.005

Cited by 24 publications

(26 citation statements)

References 35 publications

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“…112 Interestingly, in the tree shrew, similar differential gene expression patterns were observed in the choroid with three different visual manipulations (negative lens, form deprivation, and continuous darkness), implying a common myopia-inducing molecular signaling cascade, at least within the choroid. 113,114 …”

Section: The Role Of Choroid In Eye Growth Regulationmentioning

confidence: 99%

RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia

Zhang¹,

Wildsoet²

2015

Progress in Molecular Biology and Translational Science

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Myopia is the most common type of refractive errors and one of the world’s leading causes of blindness. Visual manipulations in animal models have provided convincing evidence for the role of environmental factors in myopia development. These models along with in vitro studies have provided important insights into underlying mechanisms. The key locations of the retinal pigment epithelium (RPE) and choroid make them plausible conduits for relaying growth regulatory signals originating in the retina to the sclera, which ultimately determines eye size and shape. Identifying the key signal molecules and their targets may lead to the development of new myopia control treatments. This section summarizes findings implicating the RPE and choroid in myopia development. For RPE and/or choroid, changes in morphology, activity of ion channels/transporters, as well as in gene and protein expression, have been linked to altered eye growth. Both tissues thus represent potential targets for novel therapies for myopia.

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Section: The Role Of Choroid In Eye Growth Regulationmentioning

confidence: 99%

RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia

Zhang¹,

Wildsoet²

2015

Progress in Molecular Biology and Translational Science

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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).…”

mentioning

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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“…22, 23 The expressions of BMP2 and BMP4 genes were up-regulated 1.54 and 1.48 folds respectively in choroid after 2 days of −5 D lens treatment, and in the case of BMP4, up-regulation was still evident after 11 days of −5 D lens treatment. While two days of form-deprivation treatment also induced up-regulation of BMP4 gene expression in tree shrew choroid, differential up-regulation of BMP2 gene expression was attributed in this case to a fellow eye effect, i.e., reduced expression in fellow eyes.…”

Section: Discussionmentioning

confidence: 94%

“…While two days of form-deprivation treatment also induced up-regulation of BMP4 gene expression in tree shrew choroid, differential up-regulation of BMP2 gene expression was attributed in this case to a fellow eye effect, i.e., reduced expression in fellow eyes. 23 Curiously, differential gene expression of BMP2 and BMP4 was also documented after 11 days in continuous darkness, when choroids were compared with eyes undergoing form-deprivation, negative lens treatment, and/or normal eyes, 23 and recovery from lens-induced myopia had no effect on BMP2 and BMP4 gene expression. 22 …”

Section: Discussionmentioning

confidence: 99%

Differential gene expression of BMP2 and BMP receptors in chick retina & choroid induced by imposed optical defocus

et al. 2016

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Recent studies have demonstrated the defocus sign-dependent, bidirectional gene expression regulation of bone morphogenetic proteins, BMP2, 4 and 7 in chick RPE. In this study, we examined the effects of imposed positive (+10 D) and negative (−10 D) lenses on the gene expression of these BMPs and BMP receptors (BMPR1A, BMPR1B, BMPR2) in chick retina and choroid after monocular lens treatment for 2 or 48 hours, as indicators of the roles of retinal and choroidal BMPs and receptors in postnatal eye growth regulation. In retina, although all genes were expressed, neither +10 nor −10 D lenses, worn for either 2 or 48 h, significantly altered gene expression. In contrast, treatment-related differential gene expression was detected in the choroid for both BMPs and their receptors, although interestingly, with the +10 D lens, BMP2 was up-regulated by 156.7 ± 19.7 % after 2 h, while BMPR1A was down-regulated to 82.3 ± 12.5 % only after 48 h. With the −10 D lens, only the gene expression of BMPR1B was significantly altered, being up-regulated by 162.3 ± 21.2 % after 48 h. Untreated birds showed no difference in expression between their two eyes, for any of the genes examined. The finding that retinal gene expression for BMP2, 4, 7 and their receptors are not affected by short-term optical defocus contrasts with previous observations of sign-dependent expression changes for the same genes in the RPE. The latter changes were also larger and more consistent in direction than the choroidal gene expression changes reported here. The interrelationship between these various changes and their biological significance for eye growth regulation are yet to be elucidated.

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

Cited by 24 publications

References 35 publications

RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia

RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia

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

Differential gene expression of BMP2 and BMP receptors in chick retina & choroid induced by imposed optical defocus

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