Activation of the Alternative Complement Pathway in Vitreous is Controlled by Genetics in Age-Related Macular Degeneration

2012 ◽  
Vol 53 (10) ◽  
pp. 6628 ◽  
Author(s):  
Kelly M. Loyet ◽  
Laura E. DeForge ◽  
Kenneth J. Katschke ◽  
Lauri Diehl ◽  
Robert R. Graham ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Age Related ◽  
Alternative Complement

scholarly journals Changes in extracellular matrix cause RPE cells to make basal deposits and activate the alternative complement pathway

2017 ◽  
Author(s):  
Rosario Fernandez-Godino ◽  
Kinga M. Bujakowska ◽  
Eric A. Pierce
Keyword(s):  
Extracellular Matrix ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Alternative Complement Pathway ◽  
Complement C3 ◽  
Matrix Metalloproteinase 2 ◽  
Complement Pathway ◽  
Rpe Cells ◽  
Alternative Complement

ABSTRACTThe design of efficient therapies for age-related macular degeneration (AMD) is limited by our understanding of the pathogenesis of basal deposits, which form between retinal pigment epithelium (RPE) and Bruch’s membrane (BrM) early in disease, and involve activation of the complement system. To investigate the roles of BrM, RPE and complement in AMD, we generated ARPE-19 cells with the p.R345W mutation in EFEMP1, which causes early-onset macular degeneration. The ARPE-19-EFEMP1R345W/R345W cells make abnormal extracellular matrix (ECM) that binds active complement C3 and causes the formation of basal deposits by normal human fetal (hf)RPE cells. hfRPE cells grown on abnormal ECM or BrM explants from AMD donors show chronic activation of the alternative complement pathway by excessive deposition of C3b. This process is exacerbated by impaired ECM turnover via increased matrix metalloproteinase-2 (MMP-2) activity. Therapies that target ECM synthesis and turnover and activation of C3 could be effective for early AMD.

scholarly journals THE PATHOPHYSIOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION AND THE COMPLEMENT PATHWAY AS A THERAPEUTIC TARGET

Retina ◽  
2017 ◽  
Vol 37 (5) ◽  
pp. 819-835 ◽  
Author(s):  
David S. Boyer ◽  
Ursula Schmidt-Erfurth ◽  
Menno van Lookeren Campagne ◽  
Erin C. Henry ◽  
Christopher Brittain
Keyword(s):  
Macular Degeneration ◽  
Therapeutic Target ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Complement Pathway ◽  
Age Related

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.

Sign in / Sign up

Export Citation Format

Share Document