Effect of Timolol on Optineurin Aggregation in Transformed Induced Pluripotent Stem Cells Derived From Patient With Familial Glaucoma.

Investigative Ophthalmology & Visual Science
Satoshi InagakiHideaki Hara

Abstract

To determine a chemical agent that can reduce the aggregation of optineurin (OPTN) in cells differentiated from induced pluripotent stem cells obtained from a patient with normal-tension glaucoma (NTG) caused by an E50K mutation in the OPTN gene (OPTNE50K-NTG). Retinal ganglion cells (RGCs) were created from induced pluripotent stem cells derived from a healthy individual (wild-type [WT]-iPSCs) and from a patient with NTG due to OPTNE50K (E50K-iPSCs) mutation. The death of the induced RGCs was evaluated by counting the number of TUNEL- and ATH5-positive cells. Axonal growth was determined by measuring the axonal length of TUJ1-positive cells. OPTN aggregation was assessed by measuring the OPTN-positive area by immunofluorescence and by Western blotting. Autophagic flux assay was investigated by determining the light chain 3 (LC3)B-II/LC3B-I ratio and p62 expression by Western blotting. The results showed OPTNE50K aggregation, activation of astrocytes, reduction in the number of RGCs, and enhancement of apoptotic cell death in the in vitro OPTNE50K model of NTG. Timolol was found to reduce the OPTNE50K-positive area and decreased the insoluble OPTNE50K, suggesting that it has the potential of reducing the OPTNE50K aggregation. T...Continue Reading

References

Feb 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·M HoheneggerM Freissmuth
Feb 9, 2002·Science·Tayebeh RezaieMansoor Sarfarazi
Apr 20, 2005·The Journal of Cell Biology·Daniela A SahlenderFolma Buss
Jul 27, 2005·Investigative Ophthalmology & Visual Science·Tin AungRoger A Hitchings
Feb 21, 2006·The British Journal of Ophthalmology·H A Quigley, A T Broman
Sep 6, 2007·The Journal of Clinical Investigation·Stefan Engelhardt
Sep 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Il-Man KimHoward A Rockman
Jan 20, 2009·Investigative Ophthalmology & Visual Science·Naoya MiyamotoKimitoshi Kohno
Oct 2, 2009·Clinical and Experimental Pharmacology & Physiology·James G RyallGordon S Lynch
Apr 30, 2010·Nature·Hirofumi MaruyamaHideshi Kawakami
Mar 31, 2011·Human Molecular Genetics·John H FingertEdwin M Stone
Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Budd A TuckerEdwin M Stone
Aug 27, 2011·Science Signaling·Hilla Weidberg, Zvulun Elazar
May 19, 2012·Investigative Ophthalmology & Visual Science·Qiang YangDong Feng Chen
Apr 10, 2015·IUBMB Life·Megha BansalDorairajan Balasubramanian
Apr 11, 2015·Human Molecular Genetics·Vinod SundaramoorthyJulie D Atkin
Aug 25, 2015·Experimental Eye Research·Kapil Sirohi, Ghanshyam Swarup

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Astrocytes in Repair & Regeneration

Astrocytes are glial cells found within the CNS and are able to regenerate new neurons. They become activated during CNS injury and disease. The activation leads to the transcription of new genes and the repair and regeneration of neurons. Discover the latest research on astrocytes in repair and regeneration here.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.