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 Cell Ferroptosis: New Mechanism and New Hope for Retinitis Pigmentosa

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2153
Author(s):  
Ming Yang ◽  
Kwok-Fai So ◽  
Wai-Ching Lam ◽  
Amy Cheuk Yin Lo
Keyword(s):  
Cell Death ◽  
Retinitis Pigmentosa ◽  
Photoreceptor Cell ◽  
Vision Loss ◽  
Peripheral Vision ◽  
Cell Damage ◽  
Research Area ◽  
Night Vision

Retinitis pigmentosa (RP) is a leading cause of inherited retinal degeneration, with more than 60 gene mutations. Despite the genetic heterogenicity, photoreceptor cell damage remains the hallmark of RP pathology. As a result, RP patients usually suffer from reduced night vision, loss of peripheral vision, decreased visual acuity, and impaired color perception. Although photoreceptor cell death is the primary outcome of RP, the underlying mechanisms are not completely elucidated. Ferroptosis is a novel programmed cell death, with characteristic iron overload and lipid peroxidation. Recent studies, using in vitro and in vivo RP models, discovered the involvement of ferroptosis-associated cell death, suggesting a possible new mechanism for RP pathogenesis. In this review, we discuss the association between ferroptosis and photoreceptor cell damage, and its implication in the pathogenesis of RP. We propose that ferroptotic cell death not only opens up a new research area in RP, but may also serve as a novel therapeutic target for RP.

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 SARM1 depletion rescues NMNAT1 dependent photoreceptor cell death and retinal degeneration

2020 ◽  
Author(s):  
Yo Sasaki ◽  
Hiroki Kakita ◽  
Shunsuke Kubota ◽  
Abdoulaye Sene ◽  
Tae Jun Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinal Degeneration ◽  
Photoreceptor Cell ◽  
Vision Loss ◽  
Adult Mice ◽  
Conditional Deletion ◽  
Cell Death Pathway ◽  
Human Pathology ◽  
Essential Function ◽  
Photoreceptor Death

AbstractLeber congenital amaurosis type 9 is an autosomal recessive retinopathy caused by mutations of the NAD+ synthesis enzyme NMNAT1. Despite the ubiquitous expression of NMNAT1, patients do not manifest pathologies other than retinal degeneration. Here we demonstrate that widespread NMNAT1 depletion in adult mice mirrors the human pathology, with selective loss of photoreceptors highlighting the exquisite vulnerability of these cells to NMNAT1 loss. Conditional deletion demonstrates that NMNAT1 is required within the photoreceptor. Mechanistically, loss of NMNAT1 activates the NADase SARM1, the central executioner of axon degeneration, to trigger photoreceptor death and vision loss. Hence, the essential function of NMNAT1 in photoreceptors is to inhibit SARM1, highlighting an unexpected shared mechanism between axonal degeneration and photoreceptor neurodegeneration. These results define a novel SARM1-dependent photoreceptor cell death pathway and identifies SARM1 as a therapeutic candidate for retinopathies.

scholarly journals SARM1 depletion rescues NMNAT1-dependent photoreceptor cell death and retinal degeneration

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yo Sasaki ◽  
Hiroki Kakita ◽  
Shunsuke Kubota ◽  
Abdoulaye Sene ◽  
Tae Jun Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinal Degeneration ◽  
Photoreceptor Cell ◽  
Vision Loss ◽  
Adult Mice ◽  
Conditional Deletion ◽  
Cell Death Pathway ◽  
Human Pathology ◽  
Essential Function ◽  
Photoreceptor Death

Leber congenital amaurosis type nine is an autosomal recessive retinopathy caused by mutations of the NAD+ synthesis enzyme NMNAT1. Despite the ubiquitous expression of NMNAT1, patients do not manifest pathologies other than retinal degeneration. Here we demonstrate that widespread NMNAT1 depletion in adult mice mirrors the human pathology, with selective loss of photoreceptors highlighting the exquisite vulnerability of these cells to NMNAT1 loss. Conditional deletion demonstrates that NMNAT1 is required within the photoreceptor. Mechanistically, loss of NMNAT1 activates the NADase SARM1, the central executioner of axon degeneration, to trigger photoreceptor death and vision loss. Hence, the essential function of NMNAT1 in photoreceptors is to inhibit SARM1, highlighting an unexpected shared mechanism between axonal degeneration and photoreceptor neurodegeneration. These results define a novel SARM1-dependent photoreceptor cell death pathway and identifies SARM1 as a therapeutic candidate for retinopathies.

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