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

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 Experimental Models in Neovascular Age Related Macular Degeneration

2020 ◽  
Vol 21 (13) ◽  
pp. 4627
Author(s):  
Olivia Rastoin ◽  
Gilles Pagès ◽  
Maeva Dufies
Keyword(s):  
Macular Degeneration ◽  
Experimental Models ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
In Vivo Models ◽  
Age Related ◽  
Decoy Receptors ◽  
Endothelial Growth Factor

Neovascular age-related macular degeneration (vAMD), characterized by the neo-vascularization of the retro-foveolar choroid, leads to blindness within few years. This disease depends on angiogenesis mediated by the vascular endothelial growth factor A (VEGF) and to inflammation. The only available treatments consist of monthly intravitreal injections of antibodies directed against VEGF or VEGF/VEGFB/PlGF decoy receptors. Despite their relative efficacy, these drugs only delay progression to blindness and 30% of the patients are insensitive to these treatments. Hence, new therapeutic strategies are urgently needed. Experimental models of vAMD are essential to screen different innovative therapeutics. The currently used in vitro and in vivo models in ophthalmic translational research and their relevance are discussed in this review.

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