scholarly journals Mitochondrial DNA Damage as a Potential Mechanism for Age-Related Macular Degeneration

2010 ◽  
Vol 51 (11) ◽  
pp. 5470 ◽  
Author(s):  
Pabalu P. Karunadharma ◽  
Curtis L. Nordgaard ◽  
Timothy W. Olsen ◽  
Deborah A. Ferrington
2019 ◽  
Vol 20 (10) ◽  
pp. 2374 ◽  
Author(s):  
Kai Kaarniranta ◽  
Elzbieta Pawlowska ◽  
Joanna Szczepanska ◽  
Aleksandra Jablkowska ◽  
Janusz Blasiak

Age-related macular degeneration (AMD) is a complex eye disease that affects millions of people worldwide and is the main reason for legal blindness and vision loss in the elderly in developed countries. Although the cause of AMD pathogenesis is not known, oxidative stress-related damage to retinal pigment epithelium (RPE) is considered an early event in AMD induction. However, the precise cause of such damage and of the induction of oxidative stress, including related oxidative effects occurring in RPE and the onset and progression of AMD, are not well understood. Many results point to mitochondria as a source of elevated levels of reactive oxygen species (ROS) in AMD. This ROS increase can be associated with aging and effects induced by other AMD risk factors and is correlated with damage to mitochondrial DNA. Therefore, mitochondrial DNA (mtDNA) damage can be an essential element of AMD pathogenesis. This is supported by many studies that show a greater susceptibility of mtDNA than nuclear DNA to DNA-damaging agents in AMD. Therefore, the mitochondrial DNA damage reaction (mtDDR) is important in AMD prevention and in slowing down its progression as is ROS-targeting AMD therapy. However, we know far less about mtDNA than its nuclear counterparts. Further research should measure DNA damage in order to compare it in mitochondria and the nucleus, as current methods have serious disadvantages.


Author(s):  
Jacek P. Szaflik ◽  
Katarzyna Janik-Papis ◽  
Ewelina Synowiec ◽  
Dominika Ksiazek ◽  
Magdalena Zaras ◽  
...  

Eye ◽  
1999 ◽  
Vol 13 (4) ◽  
pp. 595-596
Author(s):  
R M Andrews ◽  
B J McNeela ◽  
P Reading ◽  
P G Griffiths ◽  
P F Chinnery ◽  
...  

1998 ◽  
Vol 29 (6) ◽  
pp. 617-623 ◽  
Author(s):  
F.V. Pallardó ◽  
M. Asensi ◽  
J. García de la Asunciôn ◽  
V. Antón ◽  
A. Lloret ◽  
...  

2013 ◽  
Vol 14 (2) ◽  
pp. 2996-3010 ◽  
Author(s):  
Janusz Blasiak ◽  
Sylwester Glowacki ◽  
Anu Kauppinen ◽  
Kai Kaarniranta

2009 ◽  
Vol 50 (6) ◽  
pp. 2966 ◽  
Author(s):  
Nitin Udar ◽  
Shari R. Atilano ◽  
Masood Memarzadeh ◽  
David S. Boyer ◽  
Marilyn Chwa ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Janusz Blasiak ◽  
Malgorzata Piechota ◽  
Elzbieta Pawlowska ◽  
Magdalena Szatkowska ◽  
Ewa Sikora ◽  
...  

Age-related macular degeneration (AMD) is the main reason of blindness in developed countries. Aging is the main AMD risk factor. Oxidative stress, inflammation and some genetic factors play a role in AMD pathogenesis. AMD is associated with the degradation of retinal pigment epithelium (RPE) cells, photoreceptors, and choriocapillaris. Lost RPE cells in the central retina can be replaced by their peripheral counterparts. However, if they are senescent, degenerated regions in the macula cannot be regenerated. Oxidative stress, a main factor of AMD pathogenesis, can induce DNA damage response (DDR), autophagy, and cell senescence. Moreover, cell senescence is involved in the pathogenesis of many age-related diseases. Cell senescence is the state of permanent cellular division arrest and concerns only mitotic cells. RPE cells, although quiescent in the retina, can proliferate in vitro. They can also undergo oxidative stress-induced senescence. Therefore, cellular senescence can be considered as an important molecular pathway of AMD pathology, resulting in an inability of the macula to regenerate after degeneration of RPE cells caused by a factor inducing DDR and autophagy. It is too early to speculate about the role of the mutual interplay between cell senescence, autophagy, and DDR, but this subject is worth further studies.


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