Cameron Cowan - Academia.edu (original) (raw)

Papers by Cameron Cowan

Journal of Endodontics, 2007

Many of the proinflammatory effects of interleukin (IL)-1␤ and tumor necrosis factor-␣ (TNF-␣) ar... more Many of the proinflammatory effects of interleukin (IL)-1␤ and tumor necrosis factor-␣ (TNF-␣) are mediated through cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2). The purpose of this study was to examine the expression of IL-1␤ and TNF-␣ in COX-2-deficient osteoblasts during inflammation. Primary osteoblasts prepared from wild-type (WT) and COX-2 knockout (K/O) mice were exposed to lipopolysaccharide (LPS) and endodontic obturation materials. An enzyme-linked immunosorbent assay was used to measure cytokine levels. LPS treatment led to a significant upregulation in IL-1␤ and TNF-␣ levels in both WT and K/O cells. TNF-␣ upregulation in response to LPS was much more pronounced in K/O cells compared with WT cells (p Ͻ 0.05). All materials tested except for gutta percha caused an increase in IL-1␤ expression. In conclusion, there appears to be a positive feedback regulation between TNF-␣ and COX-2-dependent PGE2 during LPSinduced inflammatory reactions.

Investigative Ophthalmology & Visual Science, 2011

Investigative Ophthalmology & Visual Science, 2016

$Research paper thumbnail of Rare variant analyses across multiethnic cohorts identify novel genes for refractive error$

Refractive error is a complex eye condition caused by both genetic and environmental factors. Com... more Refractive error is a complex eye condition caused by both genetic and environmental factors. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests for rare variants on exome array data from the Consortium for Refractive Error and Myopia (CREAM). The dataset consisted of over 27,000 total subjects from five cohorts of Indo-European and East Asian ethnicity. We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included the retina expressed PDCD6IP, the circadian rhythm gene PER3, and P4HTM, which affects eye morphology. Future work will include functional studies and validation.

Science

Enabling near-infrared light sensitivity in a blind human retina may supplement or restore visual... more Enabling near-infrared light sensitivity in a blind human retina may supplement or restore visual function in patients with regional retinal degeneration. We induced near-infrared light sensitivity using gold nanorods bound to temperature-sensitive engineered transient receptor potential (TRP) channels. We expressed mammalian or snake TRP channels in light-insensitive retinal cones in a mouse model of retinal degeneration. Near-infrared stimulation increased activity in cones, ganglion cell layer neurons, and cortical neurons, and enabled mice to perform a learned light-driven behavior. We tuned responses to different wavelengths, by using nanorods of different lengths, and to different radiant powers, by using engineered channels with different temperature thresholds. We targeted TRP channels to human retinas, which allowed the postmortem activation of different cell types by near-infrared light.

Neuron

Large numbers of brain regions are active during behaviors. A high-resolution, brain-wide activit... more Large numbers of brain regions are active during behaviors. A high-resolution, brain-wide activity map could identify brain regions involved in specific behaviors. We have developed functional ultrasound imaging to record whole-brain activity in behaving mice at a resolution of $100 mm. We detected 87 active brain regions during visual stimulation that evoked the optokinetic reflex, a visuomotor behavior that stabilizes the gaze both horizontally and vertically. Using a genetic mouse model of congenital nystagmus incapable of generating the horizontal reflex, we identified a subset of regions whose activity was reflex dependent. By blocking eye motion in control animals, we further separated regions whose activity depended on the reflex's motor output. Remarkably, all reflex-dependent but eye motionindependent regions were located in the thalamus. Our work identifies functional modules of brain regions involved in sensorimotor integration and provides an experimental approach to monitor wholebrain activity of mice in normal and disease states.

Frontiers in Neural Circuits

Retinal ganglion cells (RGCs) are often grouped based on their functional properties. Many of the... more Retinal ganglion cells (RGCs) are often grouped based on their functional properties. Many of these functional properties, such as receptive field (RF) size, are driven by specific retinal circuits. In this report, we determined the role of the ON bipolar cell (BC) mediated crossover circuitry in shaping the center and surround of OFF RGCs. We recorded from a large population of mouse RGCs using a multielectrode array (MEA) while pharmacologically removing the ON BC-mediated crossover circuit. OFF sustained and transient responses to whole field stimuli are lost under scotopic conditions, but maintained under photopic conditions. Though photopic light responses were grossly maintained, we found that photopic light response properties were altered. Using linear RF mapping, we found a significant reduction in the antagonistic surround and a decrease in size of the RF center. Using a novel approach to separate the distinct temporal filters present in the RF center, we see that the crossover pathway contributes specifically to the sluggish antagonistic filter in the center. These results provide new insight into the role of crossover pathways in driving RGCs and also demonstrate that the distinct inputs driving the RF center can be isolated and assayed by RGC activity.

Investigative ophthalmology & visual science, Jun 1, 2016

To compare the impact of intraocular pressure (IOP) elevation on scotopic and photopic contrast s... more To compare the impact of intraocular pressure (IOP) elevation on scotopic and photopic contrast sensitivity in mice. We chronically elevated the IOP of wild-type mice via injection of polystyrene beads or acutely via injection of highly cohesive sodium hyaluronate. Some eyes with chronically elevated IOP were treated with either topical brimonidine tartrate 0.1% or brinzolamide 1%. Scotopic and photopic contrast sensitivity was assessed at peak spatiotemporal frequencies at multiple time points, with an established optokinetic technique. Retinal ganglion cell (RGC) counts were determined with an antibody to class III beta-tubulin. Correlations among IOP level, RGC count, and scotopic or photopic contrast sensitivity were performed. Six weeks of IOP elevation caused a generalized reduction of photopic contrast sensitivity and a preferential reduction of scotopic contrast sensitivity at peak spatiotemporal frequencies. The administration of brinzolamide but not brimonidine caused a si...

Cell

Highlights d Light-sensitive, multilayered human retinal organoids with functional synapses d 285... more Highlights d Light-sensitive, multilayered human retinal organoids with functional synapses d 285,441 transcriptomes from light-responsive human retinas and retinal organoids d Organoid cell types converge to adult peripheral retinal cell types d Linking retinal diseases to human retinal and retinal organoid cell types

Journal of endodontics, 2007

Prostaglandin E2 (PGE 2) is an important inflammatory mediator that plays an essential role in th... more Prostaglandin E2 (PGE 2) is an important inflammatory mediator that plays an essential role in the development and progression of periradicular diseases. Cyclooxygenase-2 (COX-2) is the inducible enzyme responsible for increased PGE 2 levels during inflammation and other pathologic processes. The purpose of this study was to determine the role of COX-2-mediated PGE 2 synthesis in osteoclast formation in response to endodontic pathogens and materials. Primary osteoblast cultures and osteoclast cultures were prepared from COX-2 knockout (K/O) and wild-type (WT) littermates. These cultured cells were exposed to lipopolysaccharide (LPS) or root canal obturation materials including gutta-percha (GP), Resilon (RS), mineral trioxide aggregates (MTAs), and AH Plus (AHϩ). Osteoclast formation was evaluated using tartrate-resistant acid phosphatase (TRAP) staining. The expression of receptor activator of NF-B ligand (RANKL) and osteoprotegerin (OPG) was determined by real-time polymerase chain reaction (PCR) analysis. It was found that in both WT and K/O cultures, treatment with LPS led to a marked increase in osteoclast formation. The number of osteoclasts formed was significantly lower in K/O cultures compared to WT cultures. Exposure to endodontic materials did not lead to any significant osteoclast formation. LPS and endodontic materials caused a decrease in both RANKL and OPG expression in WT cells. In K/O cells, the baseline levels of RANKL and OPG expression were dramatically decreased compared to the WT cells. In conclusion, COX-2-mediated PGE 2 expression is required for LPS-induced inflammatory bone resorption and maintaining the baseline level of RANKL and OPG expression. LPS-induced osteoclast formation may be independent of the RANKL pathway.