ArticleiScience2025
ZO-1/Tjp1 and ZO-2/Tjp2 deletion in retinal pigment epithelium causes progressive retinal degeneration.
Article in iScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
21 authors.
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Abstract
Tight junction protein-1 and -2 (Tjp1/ZO-1 and Tjp2/ZO-2) function as scaffold proteins within the tight junction complexes of the blood-retinal barrier (BRB). Although the breakdown of the BRB is implicated in retinopathies, the contribution of ZO-1/2 in the pathogenesis of retinopathies is unknown. To understand their role, we generated RPE-specific conditional ZO-1/2 single KOs (T1KO/T2KO) and ZO-1/2 double knockout (DKO) mice. While T1KO and T2KO did not exhibit overt retinal phenotypes, DKO demonstrated a strong retinal phenotype from 1-month post-KO induction. This includes the loss of RPE integrity and retinal thinning. Furthermore, RPE in DKO re-entered the cell cycle with upregulated YAP. At 12 months, we observed severe structural and functional retinal deterioration. In response to laser-induced damage, RPE displayed persistent hyper-proliferation, delayed wound repair, and the up-regulation of YAP. These studies confirmed the critical role of ZO-1/2 in maintaining an intact BRB and revealed a role of ZO-1/2 in wound healing.
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