scholarly journals Mitochondrial and Nuclear DNA Damage and Repair in Age-Related Macular Degeneration

2013 ◽  
Vol 14 (2) ◽  
pp. 2996-3010 ◽  
Author(s):  
Janusz Blasiak ◽  
Sylwester Glowacki ◽  
Anu Kauppinen ◽  
Kai Kaarniranta
Keyword(s):  
Dna Damage ◽  
Macular Degeneration ◽  
Nuclear Dna ◽  
Age Related Macular Degeneration ◽  
Dna Damage And Repair ◽  
Age Related

DNA damage and repair in age-related macular degeneration

2009 ◽  
Vol 669 (1-2) ◽  
pp. 169-176 ◽  
Author(s):  
Jacek P. Szaflik ◽  
Katarzyna Janik-Papis ◽  
Ewelina Synowiec ◽  
Dominika Ksiazek ◽  
Magdalena Zaras ◽  
...  
Keyword(s):  
Dna Damage ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Dna Damage And Repair ◽  
Age Related

scholarly journals Cellular Senescence in Age-Related Macular Degeneration: Can Autophagy and DNA Damage Response Play a Role?

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Janusz Blasiak ◽  
Malgorzata Piechota ◽  
Elzbieta Pawlowska ◽  
Magdalena Szatkowska ◽  
Ewa Sikora ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Macular Degeneration ◽  
Dna Damage Response ◽  
Cellular Senescence ◽  
Cell Senescence ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Damage Response

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.

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
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Potential Mechanism ◽  
Mitochondrial Dna Damage ◽  
Age Related

scholarly journals Role of Mitochondrial DNA Damage in ROS-Mediated Pathogenesis of Age-Related Macular Degeneration (AMD)

2019 ◽  
Vol 20 (10) ◽  
pp. 2374 ◽  
Author(s):  
Kai Kaarniranta ◽  
Elzbieta Pawlowska ◽  
Joanna Szczepanska ◽  
Aleksandra Jablkowska ◽  
Janusz Blasiak
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Mitochondrial Dna ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
Essential Element ◽  
Age Related Macular Degeneration ◽  
Early Event ◽  
Mitochondrial Dna Damage ◽  
Age Related

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.

scholarly journals Potential of Telomerase in Age-Related Macular Degeneration—Involvement of Senescence, DNA Damage Response and Autophagy and a Key Role of PGC-1α

2021 ◽  
Vol 22 (13) ◽  
pp. 7194
Author(s):  
Janusz Blasiak ◽  
Joanna Szczepanska ◽  
Michal Fila ◽  
Elzbieta Pawlowska ◽  
Kai Kaarniranta
Keyword(s):  
Dna Damage ◽  
Macular Degeneration ◽  
Dna Damage Response ◽  
Vision Loss ◽  
Retinal Pigment ◽  
Ectopic Expression ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Damage Response

Age-related macular degeneration (AMD), the main cause of vision loss in the elderly, is associated with oxidation in the retina cells promoting telomere attrition. Activation of telomerase was reported to improve macular functions in AMD patients. The catalytic subunit of human telomerase (hTERT) may directly interact with proteins important for senescence, DNA damage response, and autophagy, which are impaired in AMD. hTERT interaction with mTORC1 (mTOR (mechanistic target of rapamycin) complex 1) and PINK1 (PTEN-induced kinase 1) activates macroautophagy and mitophagy, respectively, and removes cellular debris accumulated over AMD progression. Ectopic expression of telomerase in retinal pigment epithelium (RPE) cells lengthened telomeres, reduced senescence, and extended their lifespan. These effects provide evidence for the potential of telomerase in AMD therapy. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may be involved in AMD pathogenesis through decreasing oxidative stress and senescence, regulation of vascular endothelial growth factor (VEGF), and improving autophagy. PGC-1α and TERT form an inhibitory positive feedback loop. In conclusion, telomerase activation and its ectopic expression in RPE cells, as well as controlled clinical trials on the effects of telomerase activation in AMD patients, are justified and should be assisted by PGC-1α modulators to increase the therapeutic potential of telomerase in AMD.

Age related macular degeneration (ARMD) – pathophysiological and clinical features and therapeutic concepts

2001 ◽  
Vol 58 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Ursula Körner-Stiefbold
Keyword(s):  
Macular Degeneration ◽  
Clinical Features ◽  
Altersbedingte Makuladegeneration ◽  
Age Related Macular Degeneration ◽  
Genetische Faktoren ◽  
Age Related ◽  
Therapeutic Concepts

Die altersbedingte Makuladegeneration (AMD) ist eine der häufigsten Ursachen für einen irreversiblen Visusverlust bei Patienten über 65 Jahre. Nahezu 30% der über 75-Jährigen sind von einer AMD betroffen. Trotz neuer Erkenntnisse in der Grundlagenforschung ist die Ätiologie, zu der auch genetische Faktoren gehören, noch nicht völlig geklärt. Aus diesem Grund sind die Behandlungsmöglichkeiten zum jetzigen Zeitpunkt noch limitiert, so dass man lediglich von Therapieansätzen sprechen kann. Die derzeit zur Verfügung stehenden Möglichkeiten wie medikamentöse, chirurgische und laser- und strahlentherapeutische Maßnahmen werden beschrieben.

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