Induction of retinopathy by fibrillar oxalate assemblies

Author:

Zaguri Dor,Shaham-Niv Shira,Naaman Efrat,Mimouni Michael,Magen Daniella,Pollack Shirley,Kreiser Topaz,Leibu Rina,Rencus-Lazar Sigal,Adler-Abramovich LihiORCID,Perlman Ido,Gazit Ehud,Zayit-Soudry Shiri

Abstract

AbstractThe formation of metabolite fibrillar assemblies represents a paradigm shift in the study of human metabolic disorders. Yet, direct clinical relevance has been attributed only to metabolite crystals. A notable example for metabolite crystallization is calcium oxalate crystals observed in various diseases, including primary hyperoxaluria. We unexpectedly observed retinal damage among young hyperoxaluria patients in the absence of crystals. Exploring the possible formation of alternative supramolecular organizations and their biological role, here we show that oxalate can form ordered fibrils with no associated calcium. These fibrils inflict intense retinal cytotoxicity in cultured cells. A rat model injected with oxalate fibrils recaptures patterns of retinal dysfunction observed in patients. Antibodies purified from hyperoxaluria patient sera recognize oxalate fibrils regardless of the presence of calcium. These findings highlight a new molecular basis for oxalate-associated disease, and to our knowledge provide the first direct clinical indication for the pathogenic role of metabolite fibrillar assemblies.

Funder

Israel Science Foundation

Publisher

Springer Science and Business Media LLC

Subject

Materials Chemistry,Biochemistry,Environmental Chemistry,General Chemistry

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