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Research article
Aparna Rao
Glaucoma, trabecular meshwork, nanotechnology, ocular regeneration
Corresponding Author
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Background
The key differences in cell deathmechanisms in the trabecular meshwork (TM) in adult moderate and severe primary glaucoma remain still unanswered. This studyexplored key differences in cell deathmechanisms in the trabecular meshwork (TM) in adult moderate and severe primary glaucoma.
Methods
Select cell death related proteins differentially expressed on mass spectrometric analysis in ex-vivo dissected TM specimens patients with severe adult primary open angle (POAG) or angle closure glaucoma (PACG) compared to controls (cadaver donor cornea), were validated for temporal changes in cell death related gene expression on in-vitro primary human TM cell culture after 48 hours (moderate) or 72 hours (severe) oxidative stress with H2O2 (400-1000uM concentration). These were compared with histone modifications after oxidative stress in HTM culture and peripheral blood of patients with moderate and severe glaucoma.
Results
Autophagy related proteins seemed to be the predominant cell death mechanism over apoptosis in ex-vivo dissected TM specimens in severe glaucoma. Analyzing HTM cell gene expression at 48 hrs and 72 hours of oxidative stress, autophagy genes were up-regulated at 48 hours of exposure > 72 hours which was in contrast to apoptosis related genes showing down-regulation at 72 hours. There was corresponding preferential abrupt upregulation of autophagy genes in the peripheral blood of the patients with severe glaucoma with associated increased expression of H3K14ac in HTM after 72 hrs of oxidative stress and in peripheral blood of severe POAG and PACG patients. Necrosis seemed to play a minimal role in cell death in moderate or severe stress in cell lines or peripheral blood.
Conclusion
A preference of autophagy over apoptosis may be underlie the mechanism of stage transition from moderate to severe glaucoma in the trabecular meshwork or peripheral blood which may be tightly regulated by epigenetic modulators. Associated epigenetic control mediating the unidirectional upregulation of autophagy in severe glaucoma requires to be explored.
Keywords
Trabecular meshwork, cell death, autophagy, apoptosis, necrosis, Glaucoma
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research article
Aparna Rao
Glaucoma, trabecular meshwork, nanotechnology, ocular regeneration
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Clinical Ophthalmology.
Version 1
Posted 18 Jun, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Ophthalmology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Clinical Ophthalmology.
Background
The key differences in cell deathmechanisms in the trabecular meshwork (TM) in adult moderate and severe primary glaucoma remain still unanswered. This studyexplored key differences in cell deathmechanisms in the trabecular meshwork (TM) in adult moderate and severe primary glaucoma.
Methods
Select cell death related proteins differentially expressed on mass spectrometric analysis in ex-vivo dissected TM specimens patients with severe adult primary open angle (POAG) or angle closure glaucoma (PACG) compared to controls (cadaver donor cornea), were validated for temporal changes in cell death related gene expression on in-vitro primary human TM cell culture after 48 hours (moderate) or 72 hours (severe) oxidative stress with H2O2 (400-1000uM concentration). These were compared with histone modifications after oxidative stress in HTM culture and peripheral blood of patients with moderate and severe glaucoma.
Results
Autophagy related proteins seemed to be the predominant cell death mechanism over apoptosis in ex-vivo dissected TM specimens in severe glaucoma. Analyzing HTM cell gene expression at 48 hrs and 72 hours of oxidative stress, autophagy genes were up-regulated at 48 hours of exposure > 72 hours which was in contrast to apoptosis related genes showing down-regulation at 72 hours. There was corresponding preferential abrupt upregulation of autophagy genes in the peripheral blood of the patients with severe glaucoma with associated increased expression of H3K14ac in HTM after 72 hrs of oxidative stress and in peripheral blood of severe POAG and PACG patients. Necrosis seemed to play a minimal role in cell death in moderate or severe stress in cell lines or peripheral blood.
Conclusion
A preference of autophagy over apoptosis may be underlie the mechanism of stage transition from moderate to severe glaucoma in the trabecular meshwork or peripheral blood which may be tightly regulated by epigenetic modulators. Associated epigenetic control mediating the unidirectional upregulation of autophagy in severe glaucoma requires to be explored.
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
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