scholarly journals A Targeted Inhibitor of the Alternative Complement Pathway Reduces Angiogenesis in a Mouse Model of Age-Related Macular Degeneration

2009 ◽  
Vol 50 (7) ◽  
pp. 3056 ◽  
Author(s):  
Ba¨rbel Rohrer ◽  
Qin Long ◽  
Beth Coughlin ◽  
R. Brooks Wilson ◽  
Yuxiang Huang ◽  
...  
Keyword(s):  
Mouse Model ◽  
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 Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 622
Author(s):  
Iswariyaraja Sridevi Gurubaran ◽  
Hanna Heloterä ◽  
Stephen Marry ◽  
Ali Koskela ◽  
Juha M. T. Hyttinen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Macular Degeneration ◽  
Complement Component ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Complement Factor ◽  
Age Related ◽  
Dry Amd

Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation.

scholarly journals Intra-vitreal αB crystallin fused to elastin-like polypeptide provides neuroprotection in a mouse model of age-related macular degeneration

2018 ◽  
Vol 283 ◽  
pp. 94-104 ◽  
Author(s):  
Parameswaran G. Sreekumar ◽  
Zhe Li ◽  
Wan Wang ◽  
Christine Spee ◽  
David R. Hinton ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Αb Crystallin

scholarly journals Progressive Age-Related Changes Similar to Age-Related Macular Degeneration in a Transgenic Mouse Model

2002 ◽  
Vol 161 (4) ◽  
pp. 1515-1524 ◽  
Author(s):  
Piroska Elizabeth Rakoczy ◽  
Dan Zhang ◽  
Terry Robertson ◽  
Nigel L. Barnett ◽  
John Papadimitriou ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Age Related Changes
Sign in / Sign up

Export Citation Format

Share Document