scholarly journals Therapeutic Potential of the Molecular Chaperone and Matrix Metalloproteinase Inhibitor Clusterin for Dry Eye

2020 ◽  
Vol 22 (1) ◽  
pp. 116
Author(s):  
M. Elizabeth Fini ◽  
Shinwu Jeong ◽  
Mark R. Wilson

Evidence is presented herein supporting the potential of the natural homeostatic glycoprotein CLU (clusterin) as a novel therapeutic for the treatment of dry eye. This idea began with the demonstration that matrix metalloproteinase MMP9 is required for damage to the ocular surface in mouse dry eye. Damage was characterized by degradation of OCLN (occludin), a known substrate of MMP9 and a key component of the paracellular barrier. Following up on this finding, a yeast two-hybrid screen was conducted using MMP9 as the bait to identify other proteins involved. CLU emerged as a strong interacting protein that inhibits the enzymatic activity of MMP9. Previously characterized as a molecular chaperone, CLU is expressed prominently by epithelia at fluid-tissue interfaces and secreted into bodily fluids, where it protects cells and tissues against damaging stress. It was demonstrated that CLU also protects the ocular surface in mouse dry eye when applied topically to replace the natural protein depleted from the dysfunctional tears. CLU is similarly depleted from tears in human dry eye. The most novel and interesting finding was that CLU binds selectively to the damaged ocular surface. In this position, CLU protects against epithelial cell death and barrier proteolysis, and dampens the autoimmune response, while the apical epithelial cell layer is renewed. When present at high enough concentration, CLU also blocks staining by vital dyes used clinically to diagnose dry eye. None of the current therapeutics have this combination of properties to “protect, seal, and heal”. Future work will be directed towards human clinical trials to investigate the therapeutic promise of CLU.

Author(s):  
Ni Made Inten Lestari ◽  
Evelyn Komaratih ◽  
Fedik A. Rantam ◽  
Yuyun Rindiastuti ◽  
Cita Rosita Sigit Prakoeswa

2020 ◽  
Vol 10 (03) ◽  
pp. 211-219
Author(s):  
Diaz-Llopis Manuel ◽  
Pinazo-Duran Maria Dolores ◽  
Diaz-Guiñon Loreto ◽  
Rahhal-Ortuño Miriam ◽  
Gallego-Pinazo Roberto ◽  
...  

2021 ◽  
Vol 22 (2) ◽  
pp. 721
Author(s):  
Youssof Eshac ◽  
Rachel L. Redfern ◽  
Vinay Kumar Aakalu

The ocular surface has the challenging responsibility of maintaining a clear moist refractive surface while protecting the eye from exogenous pathogens and the environment. Homeostasis of the ocular surface, including its innate immune components, is altered in ocular surface disease states. In this review, we focus on antimicrobial peptides and the role they play in the immune response of the ocular surface during healthy states and dry eye diseases. Antimicrobial peptides are of special interest to the study of the ocular surface because of their various roles that include microbial threat neutralization, wound healing, and immune modulation. This review explores current literature on antimicrobial peptides in ocular surface diseases and discusses their therapeutic potential in ocular surface diseases and dry eye.


Ophthalmology ◽  
2015 ◽  
Vol 122 (1) ◽  
pp. 62-71 ◽  
Author(s):  
Pasquale Aragona ◽  
M'Hammed Aguennouz ◽  
Laura Rania ◽  
Elisa Postorino ◽  
Margherita Serena Sommario ◽  
...  

Author(s):  
Carl Randall Harrell ◽  
Crissy Fellabaum ◽  
Dragica Miloradovic ◽  
Aleksandar Acovic ◽  
Dragana Miloradovic ◽  
...  

Abstract Dry eye disease (DED) is a chronic inflammatory disease of the lacrimal system and ocular surface. Considering the important role of inflammation in DED development, the main treatment strategy has shifted from hydration and lubrication of dry ocular surface to the immunomodulation and immunoregulationapproach that should address the main pathologic processes responsible for disease progression. Due to their capacity for production of immunosuppressive factors, mesenchymal stem cells (MSCs) and their secretome have been considered as potentially new agents in DED therapy. We recently developed an immunomodulatory ophthalmic solution “derived- Multiple Allogeneic Proteins Paracrine Signaling (d-MAPPS)” which activity is relied on immunosuppressive capacity of MSC-derived secretome. d-MAPPS contains MSC-derived exosomes, growth factors and immunosuppressive cytokines that are able to efficiently suppress generation of inflammatory phenotype in T cells and macrophages. Herewith, we demonstrated that d-MAPPS protected human corneal epithelial cells from chemical injury and efficiently alleviated ocular discomfort and pain in 131 DED patients during the 12-month follow-up, indicating d-MAPPS eye drops as potentially new remedy for the treatment of DED patients.


2006 ◽  
Vol 175 (4S) ◽  
pp. 469-469
Author(s):  
W. Steve Ammons ◽  
Tatyana Lukoyanova ◽  
Amber Durnal ◽  
Geoffrey Del Rosario ◽  
Alan Colowick

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