TRPA1 mediates damage of the retina induced by ischemia and reperfusion in mice
| Autor: | Pablo Pandolfo, Nicoletta Cini, Alberto Magi, Daniel Souza Monteiro de Araujo, Karin da Costa Calaza, Gianluca Mattei, Francesco De Logu, Pierangelo Geppetti, Chiara Adembri, Stanislao Rizzo, Lorenzo Landini, Malvin N. Janal, Romina Nassini |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
TRPV4 Male Cancer Research Immunology TRPV1 TRPV Cation Channels Inflammation medicine.disease_cause Article Retina Proinflammatory cytokine 03 medical and health sciences Cellular and Molecular Neuroscience Transient receptor potential channel chemistry.chemical_compound Mice 0302 clinical medicine Transient Receptor Potential Channels Retinal Diseases Ischemia medicine Animals lcsh:QH573-671 TRPA1 Cation Channel Pharmacology Cell Death Chemistry lcsh:Cytology food and beverages Retinal Cell Biology Cell biology Mice Inbred C57BL Oxidative Stress 030104 developmental biology medicine.anatomical_structure Preclinical research Reperfusion Injury Reperfusion NADPH Oxidase 1 medicine.symptom 030217 neurology & neurosurgery Oxidative stress psychological phenomena and processes |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 11, Iss 8, Pp 1-14 (2020) |
| ISSN: | 2041-4889 |
| Popis: | Oxidative stress is implicated in retinal cell injury associated with glaucoma and other retinal diseases. However, the mechanism by which oxidative stress leads to retinal damage is not completely understood. Transient receptor potential ankyrin 1 (TRPA1) is a redox-sensitive channel that, by amplifying the oxidative stress signal, promotes inflammation and tissue injury. Here, we investigated the role of TRPA1 in retinal damage evoked by ischemia (1 hour) and reperfusion (I/R) in mice. In wild-type mice, retinal cell numbers and thickness were reduced at both day-2 and day-7 after I/R. By contrast, mice with genetic deletion of TRPA1 were protected from the damage seen in their wild-type littermates. Daily instillation of eye drops containing two different TRPA1 antagonists, an oxidative stress scavenger, or a NADPH oxidase-1 inhibitor also protected the retinas of C57BL/6J mice exposed to I/R. Mice with genetic deletion of the proinflammatory TRP channels, vanilloid 1 (TRPV1) or vanilloid 4 (TRPV4), were not protected from I/R damage. Surprisingly, genetic deletion or pharmacological blockade of TRPA1 also attenuated the increase in the number of infiltrating macrophages and in the levels of the oxidative stress biomarker, 4-hydroxynonenal, and of the apoptosis biomarker, active caspase-3, evoked by I/R. These findings suggest that TRPA1 mediates the oxidative stress burden and inflammation that result in murine retinal cell death. We also found that TRPA1 (both mRNA and protein) is expressed by human retinal cells. Thus, it is possible that inhibition of a TRPA1-dependent pathway could also attenuate glaucoma-related retinal damage. |
| Databáze: | OpenAIRE |
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