Abstract：
:Careful control of iron availability in the retina is central to maintenance of iron homeostasis, as its imbalance is associated with oxidative stress and the progression of several retinopathies. Ferritin, known for its role in iron storage and detoxification, has also been proposed as an iron-transporter protein, through its binding to Scara5 and TIM2 membrane receptors. In this study, the presence and iron-related functions of TIM2 in the mouse retina were investigated. Our results revealed for the first time the presence of TIM2 receptors in the mouse retina, mainly in Müller cells. Experimental TIM2 downregulation in the mouse retina promoted, probably due to a compensatory mechanism, Scara5 overexpression that increased retinal ferritin uptake and induced iron overload. Consecutive reactive oxygen species (ROS) overproduction and vascular endothelial growth factor (VEGF) overexpression led to impaired paracellular and transcellular endothelial transport characterized by tight junction degradation and increased caveolae number. In consequence, blood-retinal barrier (BRB) breakdown and retinal edema were observed. Altogether, these results point to TIM2 as a new modulator of retinal iron homeostasis and as a potential target to counteract retinopathy.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Valença A,Mendes-Jorge L,Bonet A,Catita J,Ramos D,Jose-Cunilleras E,Garcia M,Carretero A,Nacher V,Navarro M,Ruberte Jdoi
10.1016/j.exer.2020.108292subject
Has Abstractpub_date
2021-01-01 00:00:00pages
108292eissn
0014-4835issn
1096-0007pii
S0014-4835(20)30550-9journal_volume
202pub_type
杂志文章abstract：:There is currently no available method to efficiently deliver proteins across the plasma membrane of photoreceptor or retinal pigment epithelium (RPE) cells in vivo. Thus, current clinical application of recombinant proteins in ophthalmology is limited to the use of proteins that perform their biological function extr...
journal_title：Experimental eye research
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