Ferritin But Not Iron Increases in Retina Upon Systemic Iron Overload in Diabetic and Iron-Dextran Injected Mice
Bonet, Aina (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Pampalona Sala, Judit (Universitat Autònoma de Barcelona. Centre de Biotecnologia Animal i de Teràpia Gènica (CBATEG))
José Cunilleras, Eduard (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Nacher García, Víctor (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Ruberte, Jesús (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)

Data:	2023
Resum:	Iron overload causes oxidative damage in the retina, and it has been involved in the pathogeny of diabetic retinopathy, which is one of the leading causes of blindness in the adult population worldwide. However, how systemic iron enters the retina during diabetes and the role of blood retinal barrier (BRB) in this process remains unclear. The db/db mouse, a well-known model of type 2 diabetes, and a model of systemic iron overload induced by iron dextran intraperitoneal injection, were used. Perls staining and mass spectrophotometry were used to study iron content. Western blot and immunohistochemistry of iron handling proteins were performed to study systemic and retinal iron metabolism. BRB function was assessed by analyzing vascular leakage in fundus angiographies, whole retinas, and retinal sections and by studying the status of tight junctions using transmission electron microscopy and Western blot analysis. Twenty-week-old db/db mice with systemic iron overload presented ferritin overexpression without iron increase in the retina and did not show any sign of BRB breakdown. These findings were also observed in iron dextran-injected mice. In those animals, after BRB breakdown induced by cryopexy, iron entered massively in the retina. Our results suggested that BRB protects the retina from excessive iron entry in early stages of diabetic retinopathy. Furthermore, ferritin overexpression before iron increase may prepare the retina for a potential BRB breakdown and iron entry from the systemic circulation.
Ajuts:	Ministerio de Ciencia e Innovación PID2021-122545OB-I00
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Iron overload ; Ferritin ; Diabetic retinopathy ; BRB breakdown ; Eye cryopexy
Publicat a:	Investigative Ophthalmology & Visual Science, Vol. 64 (march 2023) , ISSN 1552-5783

DOI: 10.1167/iovs.64.3.22
PMID: 36912597

14 p, 8.7 MB

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