Biology subjects

Chong, R.

Publications and source records attributed to Chong, R..

3 recordsLinked to original sources

bioRxiv2022

How Myopia and Glaucoma Influence the Biomechanical Susceptibility of the Optic Nerve Head

PurposeWe aimed to assess optic nerve head (ONH) deformations following acute intraocular pressure (IOP) elevations and horizontal eye movements (adduction and abduction) in control eyes, highly myopic (HM) eyes, HM eyes with glaucoma (HMG), and eyes with pathologic myopia alone (PM) or PM with staphyloma (PM+S). MethodsWe studied 282 eyes, comprising of 99 controls, 51 HM, 35 HMG, 21 PM and 75 PM+S eyes. For each eye, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze, (2) 20{degrees} adduction, (3) 20{degrees} abduction and (4) primary gaze with acute IOP elevation (to ~35 mmHg) achieved through ophthalmodynamometry. For each OCT volume, we automatically segmented the ONH tissues using deep learning. We performed digital volume correlation (DVC) analysis to compute IOP- and gaze-induced ONH displacements and effective strains (i.e. local deformations). All biomechanical quantities were compared across groups. ResultsUnder IOP elevation, we found that HM eyes exhibited significantly lower strains (3.9 {+/-} 2.4 %) than PM eyes (6.9 {+/-} 5.0%, p < 0.001), HMG eyes (4.7 {+/-} 1.8%, p = 0.04) and PM+S eyes (7.0 {+/-} 5.2%, p < 0.001). Under adduction, we found that HM eyes exhibited significantly lower strains (4.8% {+/-} 2.7%) than PM+S eyes (6.0 {+/-} 3.1%, p = 0.02). We also found significant associations between axial length (or refractive error) and strains - eyes with higher axial length and greater myopia were associated with higher strains. IOP-induced strains were also positively correlated with adduction-induced strains. ConclusionWe found that HMG eyes experienced significantly higher strains under IOP elevations as compared to HM eyes. Additionally, PM+S eyes experienced highest ONH strains as compared to other groups under all biomechanical loads. Our preliminary findings suggest the possibility of using a simple biomechanical test to tease out the susceptibility of HM eyes to further develop glaucoma and/or staphyloma.

bioengineering↗

bioRxiv2020

Nanobody-directed targeting of optogenetic tools reveals differential regulation of cilia length

Compartmentalization of cellular signaling forms the molecular basis of cellular behavior. The primary cilium constitutes a subcellular compartment that orchestrates signal transduction independent from the cell body. Ciliary dysfunction causes severe diseases, termed ciliopathies. Analyzing ciliary signaling and function has been challenging due to the lack of tools to temporarily manipulate and analyze ciliary signaling. Here, we describe a nanobodybased targeting approach for optogenetic tools that is applicable in vitro and in vivo and allows to specifically analyze ciliary signaling and function. Thereby, we overcome the loss of protein function observed after direct fusion to a ciliary targeting sequence. We functionally localized modifiers of cAMP signaling, i.e. the photo-activated adenylate cyclase bPAC and the light-activated phosphodiesterase LAPD, as well as the cAMP biosensor mlCNBD-FRET to the cilium. Using this approach, we studied the contribution of spatial cAMP signaling in controlling cilia length. Combining optogenetics with nanobody-based targeting will pave the way to the molecular understanding of ciliary function in health and disease.

cell biology↗

bioRxiv2018

Characterisation of the faecal virome of captive and wild Tasmanian devils using virus-like particles metagenomics and meta-transcriptomics

BackgroundThe Tasmanian devil is an endangered carnivorous marsupial threatened by devil facial tumour disease (DFTD). While research on DFTD has been extensive, little is known about the viruses present in devils, and whether any of these are of potential conservation relevance for this endangered species.\n\nMethodsUsing both metagenomics based on virus-like particle (VLP) enrichment and sequence-independent amplification (VLP metagenomics), and meta-transcriptomics based on bulk RNA sequencing, we characterised and compared the faecal viromes of captive and wild Tasmanian devils.\n\nResultsA total of 54 devil faecal samples collected from captive (n = 2) and wild (n = 4) populations were processed for virome characterisation using both approaches. We detected many novel, highly divergent viruses, including vertebrate viruses, bacteriophage and other dietary associated plant and insect viruses. In total, 18 new vertebrate viruses, including novel sapelovirus, astroviruses, bocaviruses, papillomaviruses and gammaherpesvirus were identified, as well as known mammalian pathogens including rabbit haemorrhagic disease virus 2 (RHDV2). Captive devils showed significantly lower levels of viral diversity than wild devils. Comparison of the two methodological approaches revealed substantial differences in the number and types of viruses detected, with meta-transcriptomics mainly identifying RNA viruses, and VLP metagenomics largely identifying DNA viruses.\n\nConclusionThis study has greatly expanded our knowledge of eukaryotic viruses in the Tasmanian devil and provides important baseline information that will contribute to the conservation and captive management of this endangered species. In addition, our results showed that a combination of VLP metagenomics and meta-transcriptomics may be a more comprehensive approach to virome characterisation than either method alone.

molecular biology↗