Retinal vein occlusion and paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder associated with increased risk for thrombosis and reduced life expectancy. Retinal vein occlusion (RVO) is a frequent cause of vision loss but its relationship with PNH has not been studied systematically. Patients followed up for RVO in our ophthalmology department were screened for the presence of a PNH clone in peripheral blood by means of flow cytometry. The presence of other well-documented risk factors for RVO was also analyzed. In a series of 110 patients (54 males, median age of 67) we found no evidence of PNH. Most patients (97/110) had cardiovascular risk factors and/or hyperhomocysteinemia (67/110). Inherited thrombophilias were rare (three confirmed cases). Therefore, PNH does not appear to play a role in the development of RVO. However, this finding does not necessarily apply to young patients and/or those with no conventional risk factors for RVO, due to the low number of patients in these subgroups in our population.

Hormone-specific regulation of the kidney androgen-regulated gene promoter in cultured mouse renal proximal-tubule cells.

The kidney androgen-regulated protein (KAP) is specifically expressed and differentially regulated by androgens and tri-iodothyronine (T(3)) in intact mouse early (PCT) and late (PR) proximal-tubule cells. Until now, detailed characterization of the molecular elements mediating androgen-responsive gene expression in the kidney has been hampered by the lack of appropriate cultured cell systems suitable for DNA transfection studies. In the present study we have analysed the hormone-dependent transactivation of the KAP gene promoter in immortalized differentiated PCT and PR proximal-tubule cells derived from L-PK/Tag1 transgenic mice. Transient transfection studies with different KAP promoter constructs indicated that a 224 bp-truncated fragment was sufficient to mediate cell-specific expression of the KAP promoter. Dihydrotestosterone (DHT) stimulated in an androgen-dependent manner the transactivation of KAP in PCT and PR cells, while mutation of a putative androgen-response element (ARE) sequence located at -39 bp from the transcription initiation site abolished the transactivation induced by DHT. Furthermore, insulin-like growth factor 1 (IGF-1), but not T(3), enhanced the androgen-dependent transactivation of KAP in cultured PCT cells. These results demonstrate that the short 224 bp fragment of the KAP promoter is sufficient to drive the proximal-tubule androgen-specific regulated expression of KAP and reveal synergistic interactions between IGF-1 and androgens for KAP regulation in PCT cells.