Publications by authors named "Casey J Keuthan"

RNA isolation is an essential first step for many types of molecular analyses, including reverse transcription PCR (RT-PCR)/quantitative RT-PCR (qRT-PCR), Northern blotting, microarrays, and RNA-sequencing. While many RNA purification methods have been reported, it can be challenging to extract sufficient quantity, and suitable quality, of RNA from very small amounts of tissue and/or samples containing low numbers of cells. Here we outline a total RNA isolation method that reproducibly yields high-quality RNA from human stem cell-derived retinal organoids for downstream transcriptomic analysis.

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Sirtuin 6 (SIRT6) is a member of the mammalian sirtuin family of NAD-dependent protein deacylases, homologues of the yeast silent information regulator 2 (Sir2). SIRT6 has remarkably diverse functions and plays a key role in a variety of biological processes for maintaining cellular and organismal homeostasis. In this review, our primary aim is to summarize recent progress in understanding SIRT6's functions in the retina and retinal pigment epithelium (RPE), with the hope of further drawing interests in SIRT6 to increase efforts in exploring the therapeutic potential of this unique protein in the vision field.

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A major risk factor for glaucomatous optic neuropathy is the level of intraocular pressure (IOP), which can lead to retinal ganglion cell axon injury and cell death. The optic nerve has a rostral unmyelinated portion at the optic nerve head followed by a caudal myelinated region. The unmyelinated region is differentially susceptible to IOP-induced damage in rodent models and human glaucoma.

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Article Synopsis
  • * Research involved bulk RNA-sequencing to analyze gene expression in the unmyelinated and myelinated regions of the optic nerve in mice, revealing distinct patterns and pathways affected by optic nerve injury and glaucoma.
  • * Findings indicated that the unmyelinated optic nerve had unique gene expression profiles, particularly related to astrocytes, and that gene expression changes were more extensive following nerve crush compared to glaucoma, highlighting the importance of the unmyelinated region in IOP responses.
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Alternative splicing is a fundamental and highly regulated post-transcriptional process that enhances transcriptome and proteome diversity. This process is particularly important in neuronal tissues, such as the retina, which exhibit some of the highest levels of differentially spliced genes in the body. Alternative splicing is regulated both temporally and spatially during neuronal development, can be cell-type-specific, and when altered can cause a number of pathologies, including retinal degeneration.

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Background: Though case fatality rate (CFR) is widely used to reflect COVID-19 fatality risk, its use is limited by large temporal and spatial variation. Hospital mortality rate (HMR) is also used to assess the severity of COVID-19, but HMR data is not directly available globally. Alternative metrics are needed for COVID-19 severity and fatality assessment.

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Peroxisome proliferator-activated receptors (PPARs) are a family of three nuclear hormone receptors (PPARα, PPARδ, and PPARγ) that are known to regulate expression of lipid metabolism and oxidative stress genes. Given their role in reducing oxidative stress in a variety of tissues, these genes are likely important for retinal homeostasis. This hypothesis has been further supported by recent studies suggesting that PPAR-activating drugs are protective against retinal degenerations.

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Retinal degenerations are a large cluster of diseases characterized by the irreversible loss of light-sensitive photoreceptors that impairs the vision of 9.1 million people in the US. An attractive treatment option is to use gene therapy to deliver broad-spectrum neuroprotective factors.

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