Tick‐over mediated complement activation is sufficient to cause basal deposit formation in cell‐based models of macular degeneration

2021 ◽  
Author(s):  
Blanca Chinchilla ◽  
Parthena Foltopoulou ◽  
Rosario Fernandez‐Godino
Keyword(s):  
Macular Degeneration ◽  
Complement Activation ◽  
Deposit Formation

scholarly journals Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donita L. Garland ◽  
Eric A. Pierce ◽  
Rosario Fernandez-Godino
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Deposit Formation ◽  
Genetic Ablation ◽  
Age Related ◽  
Complement Dysregulation

AbstractThe complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1-associated macular degeneration. In this study, we have used double mutant Efemp1R345W/R345W:C5-/- mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.

scholarly journals Local complement activation in aqueous humor in patients with age-related macular degeneration

2017 ◽  
Vol 89 ◽  
pp. 163 ◽  
Author(s):  
Michael Kirschfink ◽  
Tina Schick ◽  
Marlin Steinhauer ◽  
Alexander Aslanidis ◽  
Lebriz Altay ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Aqueous Humor ◽  
Complement Activation ◽  
Age Related Macular Degeneration ◽  
Age Related

Complement Activation and Inflammatory Processes in Drusen Formation and Age Related Macular Degeneration

2001 ◽  
Vol 73 (6) ◽  
pp. 887-896 ◽  
Author(s):  
Lincoln V Johnson ◽  
William P Leitner ◽  
Michelle K Staples ◽  
Don H Anderson
Keyword(s):  
Macular Degeneration ◽  
Complement Activation ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Inflammatory Processes

scholarly journals A Novel Complotype Combination Associates with Age-Related Macular Degeneration and High Complement Activation Levels in vivo

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Constantin C. Paun ◽  
Yara T. E. Lechanteur ◽  
Joannes M. M. Groenewoud ◽  
Lebriz Altay ◽  
Tina Schick ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Complement Activation ◽  
Age Related Macular Degeneration ◽  
Age Related

Age-related Macular Degeneration and Complement Activation–related Diseases

Ophthalmology ◽  
2008 ◽  
Vol 115 (11) ◽  
pp. 1904-1910 ◽  
Author(s):  
Dorothea Nitsch ◽  
Ian Douglas ◽  
Liam Smeeth ◽  
Astrid Fletcher
Keyword(s):  
Macular Degeneration ◽  
Complement Activation ◽  
Age Related Macular Degeneration ◽  
Age Related
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