Biology subjects

Harvey, A. R.

Publications and source records attributed to Harvey, A. R..

6 recordsLinked to original sources

bioRxiv2026

Characterising retinal function with optomotor visual performance in P23H rodent models of retinitis pigmentosa

Rhodopsin (RHO) P23H is one of the most common mutations causing autosomal dominant retinitis pigmentosa (adRP), yet the relationship between retinal electrophysiology, structure and visually guided behaviour in rodent models remains unclear. We characterised changes in heterozygous P23H (Sakami line) mice and P23H line 3 (P23H-3) rats using full-field electroretinography (ERG), optomotor response (OMR) assays and, in rats, optical coherence tomography (OCT). ERG assessed rod- and cone-mediated responses relative to wild-type controls, whereas OMR under scotopic and photopic conditions quantified contrast sensitivity and visual acuity. In P23H mice, scotopic ERG responses were significantly reduced from postnatal day 16 and declined further from 4 months. Scotopic OMR contrast sensitivity remained largely preserved until 2 months, and photopic acuity was comparable to wild-type up to 6 months. In 13-week-old P23H-3 rats, ERG amplitudes were significantly reduced, and OCT revealed retinal thinning. OMR showed a decline in contrast sensitivity at 7 and 15 weeks, whereas photopic acuity was maintained. Thus, in both models, electrophysiological and structural abnormalities precede detectable OMR deficits, with implications for the selection of outcome measures in preclinical studies. Summary StatementThis study compares electrical and behavioural measures of vision in rodent models of inherited blindness, revealing that retinal dysfunction appears well before measurable vision loss.

animal behavior and cognition↗

bioRxiv2025

Prolonged Heat Treated Mesenchymal Precursor Cells Induce Positive Outcomes Following Transplantation in Cervical Spinal Cord Injury.

Cellular transplantation therapies have been extensively used in experimental spinal cord injury research. However, there is no consensus as to what the most effective cellular controls for the therapeutic cell of interest are. For this reason, we examined if dead cells obtained through prolonged heat treatment can act as an appropriate cellular control for intravenously injected Sca-1+ mesenchymal precursor cells (MPCs) in C5 unilateral contusion cervical spinal cord injury. This was tested in single intravenous MPCs injection alone or intravenous MPCs plus intraspinal neural stem cells (NSCs) combinatory transplantation studies. MPCs were isolated from the compact bone of FVB mice while NSCs were isolated from the subventricular zone of luciferase-GFP transgenic FVB mice. Dead MPCs were obtained by heating at 72{degrees}C for at least 12 hours. In the MPCs only transplant study, injured mice received an injection of 1x106 dead or live MPCs D1 post-injury. Mice were then sacrificed at 8 weeks post-injury. In this study, intravenous injections of dead MPCs showed no statistical difference in injured paw usage compared to live MPCs, but behavior was improved compared to the media vehicle only control at D7 and D21. In the combinatory MPCs plus NSCs transplant study, injured mice received an intravenous injection of 1x106 dead or live MPCs D1 post-injury followed by intraspinal injection of 100,000 NSCs at D3 or D7 post-injury. Another two cohorts of mice received only NSCs at D3 or D7 post-injury. Mice were then sacrificed at 6 weeks post-injury. In this study, there was no functional difference in any of the groups in the dual injection study. Morphologically, mice receiving IV injection of dead MPCs had a smaller lesion size compared to the vehicular control, but the lesion size was larger than that of the lesion size in mice receiving live MPC injection. Dead cells elicited functional and anatomical benefits for the spinal cord injured mouse. In summary, dead cells obtained through prolonged heat treatment proved to be inconsistent and not optimal for use as cellular controls for cell transplantation studies in spinal cord injury but provides positive evidence for non-transplantation based cell therapies.

neuroscience↗

bioRxiv2025

Combined Transplantation of Mesenchymal Progenitor and Neural Stem Cells to repair cervical spinal cord injury.

Mesenchymal progenitor cells (MPC) are effective in reducing tissue loss, preserving white matter and improving forelimb function after spinal cord injury (SCI) (White et al., 2016). We proposed that by preconditioning the mouse by intravenous delivery (IV) of MPCs for 24 hours following SCI that this would provide a more favorable tissue milieu for NSC intraspinal bridging transplantation at day 3 and day 7. In com-bination these transplants will provide better anatomical and functional outcomes. The intravenous MSCs would provide cell protection and reduce inflammation. NSCs would provide a tissue bridge for axonal regeneration and myelination and reconnect long tract spinal pathways. Results showed that initial protection of the injury site by IV MPCs transplantation resulted in no increased survival of the NSCs transplanted at Day 7. However, integration of transplanted NSCs was increased at the Day 3 time point indicating MPCs influence very early immune signaling. We show in this study that MPC transplantation resulted in a co-operative NSC cell survival improvement at Day 3 post SCI. In addition to increased NSC survival at day 3 there was an increase in NSC derived mature oligodendrocytes at this early time point. In vitro analysis confirmed MPC driven oligodendrocyte differentiation which was statistically increased when compared to control NSC only cultures. These observations provide important information about the combination, delivery, and timing of two cellular therapies in treating SCI. This study provides important new data on understanding the MPC inflammatory signaling within the host tissue and time points for cellular transplantation survival and oligodendroglia differentiation. These results demonstrate that MPC transplantation can alter the therapeutic window for intraspinal transplantation by controlling both the circulating inflammatory response and local tissue milieu.

neuroscience↗

bioRxiv2018

Dye-free retinal angiography using blood-oxygenation modulation

Fluorescence angiography (FA) is widely used for studying and diagnosing abnormalities in the retinal blood circulation, but has associated risks of nausea, skin irritation, and even death. We describe a new non-invasive angiography technique: Blood Oxygenation Modulation Angiography, in which multispectral imaging of a transient perturbation in blood-oxygen saturation, yields angiography sequences similar to FA, including key features such as sequential filling of choroidal and retinal-vessels, which underpin assessment of circulation health. This is the first non-invasive angiography technique capable of visualizing these circulation features.

biophysics↗

bioRxiv2018

Millimetre wave radiation activates leech nociceptors via TRPV1-like receptor sensitisation

Due to new applications such as wireless communications, security scanning, and imaging the presence of artificially generated high frequency (30-300 GHz) millimetre-wave (MMW) signals in the environment is increasing. Although safe exposure levels have been set by studies involving direct thermal damage to tissue, there is evidence that MMWs can have an impact on cellular function, including neurons. Earlier in vitro studies have shown that exposure levels well below the recommended safe limit of 1mW/cm2 cause changes in the action potential (AP) firing rate, resting potential, and AP pulse shape of sensory neurons in leech preparations, as well as alter neuronal properties in rat cortical brain slices; these effects differ from changes induced by direct heating. In this paper we examine continuous MMW power (up to 80 mW/cm2 at 60 GHz) and evaluate the responses in the thermosensitive primary nociceptors of the medicinal leech (genus Richardsonianus Australis). The results show that MMW exposure causes an almost two-fold decrease in the threshold for activation of the AP compared with conductive heating (3.6{+/-}0.4 mV vs. 6.5{+/-}0.4 mV respectively). Our analysis suggests that MMW exposure mediated threshold alterations are not caused by enhancement of voltage gated sodium and potassium conductance. Moreover, it appears that MMW exposure has a modest suppressing effect on membrane excitability. We propose that the reduction in AP threshold can be attributed to sensitization of the TRPV1-like receptor in the leech nociceptor. In silico modelling supported the experimental findings. Our results provide evidence that MMW exposure stimulates specific receptor responses that differ from direct conductive heating, fostering the need for additional studies.

biophysics↗

bioRxiv2018

Low-cost, sub-micron resolution, wide-field computational microscopy using opensource hardware

The revolution in low-cost consumer photography and computation provides fertile opportunity for a disruptive reduction in the cost of biomedical imaging. Conventional approaches to low-cost microscopy are fundamentally restricted, however, to modest field of view (FOV) and/or resolution. We report a low-cost microscopy technique, implemented with a Raspberry Pi single-board computer and color camera combined with Fourier ptychography (FP), to computationally construct 25-megapixel images with sub-micron resolution. New image-construction techniques were developed to enable the use of the low-cost Bayer color sensor, to compensate for the highly aberrated re-used camera lens and to compensate for misalignments associated with the 3D-printed microscope structure. This high ratio of performance to cost is of particular interest to high-throughput microscopy applications, ranging from drug discovery and digital pathology to health screening in low-income countries. 3D models and assembly instructions of our microscope are made available for open source use.

pathology↗