Techniques to Quantify cGMP Dysregulation as a Common Pathway Associated with Photoreceptor Cell Death in Retinitis Pigmentosa

2019 ◽  
pp. 407-411
Author(s):  
Paul Yang ◽  
Rachel A. Lockard ◽  
Hope Titus
Keyword(s):  
Cell Death ◽  
Retinitis Pigmentosa ◽  
Photoreceptor Cell ◽  
Common Pathway

scholarly journals Knockout of ccr2 alleviates photoreceptor cell death in a model of retinitis pigmentosa

2012 ◽  
Vol 104 ◽  
pp. 39-47 ◽  
Author(s):  
Congrong Guo ◽  
Atsushi Otani ◽  
Akio Oishi ◽  
Hiroshi Kojima ◽  
Yukiko Makiyama ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinitis Pigmentosa ◽  
Photoreceptor Cell

Apoptosis, retinitis pigmentosa, and degeneration

1994 ◽  
Vol 72 (11-12) ◽  
pp. 489-498 ◽  
Author(s):  
Paul Wong
Keyword(s):  
Cell Death ◽  
Retinitis Pigmentosa ◽  
Retinal Degeneration ◽  
Photoreceptor Cell ◽  
Retinal Cell ◽  
Current Evidence ◽  
Cell Degeneration ◽  
Genetic Lesion ◽  
Common Causes ◽  
Active Cell Death

The mechanism of photoreceptor cell death in different inherited retinal degenerations is not fully understood. Mutations in a number of different genes (such as rhodopsin, the beta subunit of cGMP phosphodiesterase, and peripherin) have been identified as the primary genetic lesion in different forms of human retinitis pigmentosa, one of the most common causes of inherited blindness. In all cases the manifestation of the disorder regardless of the specific primary genetic lesion is similar, resulting in photoreceptor cell degeneration and blindness. A recent hypothesis is that the active photoreceptor cell death, which is characteristic of these genetically distinct disorders, is mediated by a common induction of apoptosis. In the present review, the current evidence for active cell death during retinal cell death in several different rodent models of retinitis pigmentosa and retinal degeneration is examined.Key words: retinal degeneration, apoptosis, retinitis pigmentosa, clusterin, DNA fragmentation.

scholarly journals Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration

2019 ◽  
Author(s):  
Katherine J. Wert ◽  
Gabriel Velez ◽  
Kanchustambham Vijayalakshmi ◽  
Vishnu Shankar ◽  
Jesse D. Sengillo ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinitis Pigmentosa ◽  
Ketogenic Diet ◽  
Proteomic Analysis ◽  
Photoreceptor Cell ◽  
Neuroprotective Effect ◽  
Tca Cycle ◽  
Ionization Mass ◽  
Molecular Pathways ◽  
Aconitic Acid

AbstractNeurodegenerative diseases are debilitating, incurable disorders caused by progressive neuronal cell death. Retinitis pigmentosa (RP) is a blinding neurodegenerative disease that results in retinal photoreceptor cell death and progresses to the loss of the entire neural retinal network. We previously found that proteomic analysis of the adjacent vitreous serves as way to indirectly biopsy the neural retina and identify changes in the retinal proteome. We therefore analyzed protein expression in liquid vitreous biopsies from autosomal recessive retinitis pigmentosa (arRP) patients with PDE6A mutations and arRP mice with Pde6ɑ mutations. Proteomic analysis of retina and vitreous samples identified molecular pathways affected at the onset of photoreceptor cell death. Based on affected molecular pathways, arRP mice were treated with a ketogenic diet or metabolites involved in fatty-acid synthesis, oxidative phosphorylation, and the tricarboxylic acid (TCA) cycle. Dietary supplementation of a single metabolite, ɑ-ketoglutarate, increased docosahexaeonic acid (DHA) levels, provided neuroprotection, and enhanced visual function in arRP mice. A ketogenic diet delayed photoreceptor cell loss, while vitamin B supplementation had a limited effect. Finally, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) revealed restoration of key metabolites that correlated with our proteomic findings: pyrimidine and purine metabolism (uridine, dihydrouridine, and thymidine), glutamine and glutamate (glutamine/glutamate conversion), and succinic and aconitic acid (TCA cycle). This study demonstrates that replenishing TCA cycle metabolites via oral supplementation prolongs vision and provides a neuroprotective effect on the photoreceptor cells and inner retinal network.One Sentence SummaryThe study shows protein and metabolite pathways affected during neurodegeneration and that replenishing metabolites provides a neuroprotective effect on the retina.

scholarly journals Absence of Sigma 1 Receptor Accelerates Photoreceptor Cell Death in a Murine Model of Retinitis Pigmentosa

2017 ◽  
Vol 58 (11) ◽  
pp. 4545 ◽  
Author(s):  
Jing Wang ◽  
Alan Saul ◽  
Xuezhi Cui ◽  
Penny Roon ◽  
Sylvia B. Smith
Keyword(s):  
Cell Death ◽  
Retinitis Pigmentosa ◽  
Murine Model ◽  
Photoreceptor Cell ◽  
Sigma 1 Receptor ◽  
Sigma 1

scholarly journals PKG activity causes photoreceptor cell death in two retinitis pigmentosa models

2009 ◽  
Vol 108 (3) ◽  
pp. 796-810 ◽  
Author(s):  
François Paquet-Durand ◽  
Stefanie M. Hauck ◽  
Theo van Veen ◽  
Marius Ueffing ◽  
Per Ekström
Keyword(s):  
Cell Death ◽  
Retinitis Pigmentosa ◽  
Photoreceptor Cell

scholarly journals Intravitreal Injection of Proinsulin-Loaded Microspheres Delays Photoreceptor Cell Death and Vision Loss in therd10Mouse Model of Retinitis Pigmentosa

2016 ◽  
Vol 57 (8) ◽  
pp. 3610 ◽  
Author(s):  
Carolina Isiegas ◽  
Jorge A. Marinich-Madzarevich ◽  
Miguel Marchena ◽  
José M. Ruiz ◽  
María J. Cano ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinitis Pigmentosa ◽  
Intravitreal Injection ◽  
Photoreceptor Cell ◽  
Vision Loss

scholarly journals Modelling and rescue of RP2 Retinitis Pigmentosa using iPSC Derived Retinal Organoids

2020 ◽  
Author(s):  
Amelia Lane ◽  
Katarina Jovanovic ◽  
Ciara Shortall ◽  
Daniele Ottaviani ◽  
Anna Brugulat Panes ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinitis Pigmentosa ◽  
Photoreceptor Cell ◽  
Outer Nuclear Layer ◽  
Disease Model ◽  
Retinal Disease ◽  
Severe Form ◽  
Rod Photoreceptor ◽  
Knock Out ◽  
Induced Pluripotent

SummaryRP2 mutations cause a severe form of X-linked retinitis pigmentosa (XLRP). The mechanism of RP2 associated retinal degeneration in humans is unclear, and animal models of RP2 XLRP do not recapitulate this severe phenotype. Here, we developed gene edited isogenic RP2 knock-out (RP2 KO) induced pluripotent stem cells (iPSC) and RP2 patient derived iPSC to produce 3D retinal organoids as a human retinal disease model. Strikingly, the RP2 KO and RP2 patient derived organoids showed a peak in rod photoreceptor cell death at day 150 (D150) with subsequent thinning of the organoid outer nuclear layer (ONL) by D180 of culture. AAV mediated gene augmentation with human RP2 rescued the degeneration phenotype of the RP2 KO organoids, to prevent ONL thinning and restore rhodopsin expression. Notably, these data show that 3D retinal organoids can be used to model photoreceptor degeneration and test potential therapies to prevent photoreceptor cell death.

scholarly journals Necrotic cone photoreceptor cell death in retinitis pigmentosa

2015 ◽  
Vol 6 (12) ◽  
pp. e2038-e2038 ◽  
Author(s):  
Y Murakami ◽  
Y Ikeda ◽  
S Nakatake ◽  
J W Miller ◽  
D G Vavvas ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinitis Pigmentosa ◽  
Photoreceptor Cell ◽  
Cone Photoreceptor

scholarly journals Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa.

1994 ◽  
Vol 91 (3) ◽  
pp. 974-978 ◽  
Author(s):  
C. Portera-Cailliau ◽  
C. H. Sung ◽  
J. Nathans ◽  
R. Adler
Keyword(s):  
Cell Death ◽  
Retinitis Pigmentosa ◽  
Mouse Models ◽  
Photoreceptor Cell
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