Regulation of Stem Cell Properties of Müller Glia by JAK/STAT and MAPK Signaling in the Mammalian Retina

In humans and other mammals, the neural retina does not spontaneously regenerate, and damage to the retina that kills retinal neurons results in permanent blindness. In contrast to embryonic stem cells, induced pluripotent stem cells, and embryonic/fetal retinal stem cells, Müller glia offer an intrinsic cellular source for regenerative strategies in the retina. Müller glia are radial glial cells within the retina that maintain retinal homeostasis, buffer ion flux associated with phototransduction, and form the blood/retinal barrier within the retina proper. In injured or degenerating retinas, Müller glia contribute to gliotic responses and scar formation but also show regenerative capabilities that vary across species. In the mammalian retina, regenerative responses achieved to date remain insufficient for potential clinical applications. Activation of JAK/STAT and MAPK signaling by CNTF, EGF, and FGFs can promote proliferation and modulate the glial/neurogenic switch. However, to achieve clinical relevance, additional intrinsic and extrinsic factors that restrict or promote regenerative responses of Müller glia in the mammalian retina must be identified. This review focuses on Müller glia and Müller glial-derived stem cells in the retina and phylogenetic differences among model vertebrate species and highlights some of the current progress towards understanding the cellular mechanisms regulating their regenerative response

In Vivo Imaging of the Retina, Choroid, and Optic Nerve Head in Guinea Pigs

<p><i>Purpose:</i> Guinea pigs are increasingly being used as a model of myopia, and may also represent a novel model of glaucoma. Here, optical coherence tomography (OCT) imaging was performed in guinea pigs. <i>In vivo</i> measurements of retinal, choroidal, and optic nerve head parameters were compared with histology, and repeatability and interocular variations were assessed.</p> <p><i>Methods:</i> OCT imaging and histology were performed on adult guinea pigs (<i>n</i> = 9). Using a custom program in MATLAB, total retina, ganglion cell/nerve fiber layer (GC/NFL), outer retina, and choroid thicknesses were determined. Additionally, Bruch’s membrane opening (BMO) area and diameter, and minimum rim width were calculated. Intraobserver, interocular, and intersession coefficients of variation (CV) and intraclass correlation coefficients (ICC) were assessed.</p> <p><i>Results:</i> Retina, GC/NFL, outer retina and choroid thicknesses from <i>in vivo</i> OCT imaging were 147.7 ± 5.8 μm, 59.2 ± 4.5 μm, 72.4 ± 2.4 μm, and 64.8 ± 11.6 μm, respectively. Interocular CV ranged from 1.8% to 11% (paired <i>t</i>-test, <i>p</i> = 0.16 to 0.81), and intersession CV ranged from 1.1% to 5.6% (<i>p</i> = 0.12 to 0.82), with the choroid showing the greatest variability. BMO area was 0.192 ± 0.023 mm², and diameter was 493.79 ± 31.89 μm, with intersession CV of 3.3% and 1.7%, respectively. Hyper reflective retinal layers in OCT correlated with plexiform and RPE layers in histology.</p> <p><i>Conclusion:</i><i>In vivo</i> OCT imaging and quantification of guinea pig retina and optic nerve head parameters were repeatable and similar between eyes of the same animal. <i>In vivo</i> visibility of retinal cell layers correlated well with histological images.</p> <p><b>Abbreviations:</b> optic nerve head (ONH), retinal ganglion cell (RGC), spectral domain optical coherence tomography (SD-OCT), enhanced depth imaging (EDI), minimum rim width (MRW), hematoxylin and eosin (H & E)</p

Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7