Two cases of congenital simple hamartoma of the retinal pigment epithelium.

PURPOSE: Congenital simple hamartoma of the retinal pigment epithelium (CSHRPE) is a rare fundus condition. Two cases of CSHRPE are reported. METHODS: The clinical findings and biomicroscopy, fluorescein angiography, optical coherence tomography (OCT), and ultrasonography features differentiating this pigmented macular tumor from uveal melanoma or retinal pigment epithelium (RPE) anomalies and neoplasms are discussed. RESULTS: Two patients were observed with a pigmented macular lesion. Sharply demarcated transretinal lesions were seen in the macula of both patients, arising from the RPE. The periphery of the lesion in Case 1 was flat and black; the central portion was elevated and fibrotic with a central vitreous strand. A narrow crescent of RPE atrophy was noted temporally. Optical coherence tomography of both lesions showed the typical findings of CSHRPE: high reflectivity, irregular surface, abrupt borders, and full-thickness retinal shadowing. The decision was made to observe the lesions. During follow-up, the lesions remained unchanged. CONCLUSION: The unusual finding of CSHRPE associated with RPE atrophy makes the differentiation between CSHRPE and hyperplasia of the RPE even more difficult. Noninvasive OCT has a major role in the diagnosis of CSHRPE.

TWISTED DWARF1, a unique plasma membrane-anchored immunophilin-like protein, interacts with Arabidopsis multidrug resistance-like transporters AtPGP1 and AtPGP19.

Null-mutations of the Arabidopsis FKBP-like immunophilin TWISTED DWARF1 (TWD1) gene cause a pleiotropic phenotype characterized by reduction of cell elongation and disorientated growth of all plant organs. Heterologously expressed TWD1 does not exhibit cis-trans-peptidylprolyl isomerase (PPIase) activity and does not complement yeast FKBP12 mutants, suggesting that TWD1 acts indirectly via protein-protein interaction. Yeast two-hybrid protein interaction screens with TWD1 identified cDNA sequences that encode the C-terminal domain of Arabidopsis multidrug-resistance-like ABC transporter AtPGP1. This interaction was verified in vitro. Mapping of protein interaction domains shows that AtPGP1 surprisingly binds to the N-terminus of TWD1 harboring the cis-trans peptidyl-prolyl isomerase-like domain and not to the tetratrico-peptide repeat domain, which has been shown to mediate protein-protein interaction. Unlike all other FKBPs, TWD1 is shown to be an integral membrane protein that colocalizes with its interacting partner AtPGP1 on the plasma membrane. TWD1 also interacts with AtPGP19 (AtMDR1), the closest homologue of AtPGP1. The single gene mutation twd1-1 and double atpgp1-1/atpgp19-1 (atmdr1-1) mutants exhibit similar phenotypes including epinastic growth, reduced inflorescence size, and reduced polar auxin transport, suggesting that a functional TWD1-AtPGP1/AtPGP19 complex is required for proper plant development.