Purpose: We studied clinical phenotyping and TEAD1 expression in mice and humans to gain a better understanding of the primary origin in the pathogenesis of circumpapillary dysgenesis of the pigment epithelium.
Design: Observational case series and experimental study.
Participants: Three female patients from an affected family were included for phenotypic study. Mice and human tissues were used for biochemistry and immunohistochemistry studies.
Methods: We performed genetic analyses and longitudinal clinical, imaging, and electrophysiologic studies in a 3-generation family. Western blotting and immunohistochemistry were used to detect TEAD1 expression in mice and human retinal tissues.
Main outcome measures: Autofluorescence and optical coherence tomography (OCT) imaging were compared and reviewed from 3 patients. TEAD1 expression was compared in different tissues from mice and human samples.
Results: A point mutation at T1261 in TEAD1 was detected in the mother. Autofluorescence and OCT imaging studies revealed choroid is involved earlier than retinal pigment epithelium (RPE). From immunoblot analysis, we discovered that TEAD1 and its cofactors YAP65 and FOXA2 are expressed in the choroid. Immunohistochemical analysis on frozen sections of mouse retina supports immunoblot results.
Conclusions: The primary cellular origin of circumpapillary dysgenesis of the pigment epithelium is within the choroid instead of the pigment epithelium. The loss of the RPE and photoreceptors in later stages of the disease is a secondary consequence of choroidal degeneration. Studies of the downstream targets of TEAD1 in choroidal cells will provide promising new research opportunities for the development of treatments for choroidal diseases.
Financial disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.