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Bestrophinopathies are a group of clinically distinct inherited retinal dystrophies that lead to the gradual loss of vision in and around the macular area. There are no treatments for patients suffering from bestrophinopathies, and no measures can be taken to prevent visual deterioration in those who have inherited disease-causing mutations. Bestrophinopathies are caused by mutations in the Bestrophin1 gene (BEST1), a protein found exclusively in the retinal pigment epithelial (RPE) cells of the eye. Mutations in BEST1 affect the function of the RPE leading to the death of overlying retinal cells and subsequent vision loss. The pathogenic mechanisms arising from BEST1 mutations are still not fully understood, and it is not clear how mutations in BEST1 lead to diseases with distinct clinical features. This chapter discusses BEST1, the use of model systems to investigate the effects of mutations and the potential to investigate individual bestrophinopathies using induced pluripotent stem cells.

Mitochondrial-nuclear communication is critical for maintaining mitochondrial activity under stress conditions. Adaptation of the mitochondrial-nuclear network to changes in the intracellular oxidation and reduction milieu is critical for the survival of retinal and retinal pigment epithelial (RPE) cells, in relation to their high oxygen demand and rapid metabolism. However, the generation and transmission of the mitochondrial signal to the nucleus remain elusive. Previously, our in vivo study revealed that prohibitin is upregulated in the retina, but downregulated in RPE cells in the aging and diabetic model. In this study, the functional role of prohibitin in the retina and RPE cells was examined using biochemical methods, including a lipid binding assay, two-dimensional gel electrophoresis, immunocytochemistry, Western blotting, and a knockdown approach. Protein depletion by siRNA characterized prohibitin as an anti-apoptotic molecule in mitochondria, while the lipid binding assay demonstrated subcellular communication between mitochondria and the nucleus under oxidative stress. The changes in the expression and localization of mitochondrial prohibitin triggered by reactive oxygen species are crucial for mitochondrial integrity. We propose that prohibitin shuttles between mitochondria and the nucleus as an anti-apoptotic molecule and a transcriptional regulator in a stress environment in the retina and RPE cells.

A case of bilateral ureteral and renal agenesis is presented in a male infant at term that showed no other gross abnormalities. A review of the incidence showed that this malformation, once considered exceedingly rare, is present much more frequently. A review of the two characteristically associated anomalies, abnormality of facies and hypoplasia of the lungs, is given. This is the only reported case in the literature in which there were intact membranes and a normal amount of amniotic fluid. There can be little doubt, from this case, that amniotic fluid does appear in the complete absence of both kidneys. No reports have been found which can throw any light as to the real cause of death in these infants. It does not appear that these infants die in uremia. It is hoped with this presentation and review that more cases will be diagnosed at the time of delivery and that an adequate work-up (blood chemistry and analysis of amniotic fluid) will be done so that a fuller understanding of the early neonatal as well as intrauterine physiology might be brought about.

This study was carried out to correlate changes in urinary estrogens and the response of the adrenal glands to administration of human chorionic gonadotropin (HCG) and acetocorticotropic hormone (ACTH) in 5 castrated female volunteers. A total of 50,000 U. of HCG was administered intramuscularly to each. Two weeks later, each received a total of 120 U. of gel of ACTH intramuscularly. Vaginal smears and urinary hormone assays were done before and after treatment. Administration of HCG did not produce any changes in urinary hormone levels or in vaginal smears. ACTH produced increases in 24 hour urinary 17-ketosteroids, 17-hydroxycorticoids, and total estrogens, with a shift to the right in the maturation index of the vaginal smear.