Mutation in the ßA3/A1-crystallin gene impairs phagosome degradation in the retinal pigmented epithelium of the rat.

Phagocytosis of the shed outer segment discs of photoreceptors is a major function of the retinal pigmented epithelium (RPE). We demonstrate for the first time that ßA3/A1-crystallin, a major structural protein of the ocular lens, is expressed in RPE cells. Further, by utilizing the Nuc1 rat, in which the ßA3/A1-crystallin gene is mutated, we show that this protein is required by RPE cells for proper degradation of outer segment discs that have been internalized in phagosomes. We also demonstrate that in wild-type RPE, ßA3/A1-crystallin is localized to the lysosomes. However, in the Nuc1 RPE, ßA3/A1-crystallin fails to translocate to the lysosomes, perhaps because misfolding of the mutant protein masks sorting signals required for proper trafficking. The digestion of phagocytized outer segments requires a high level of lysosomal enzyme activity, and cathepsin D, the major enzyme responsible for proteolysis of the outer segments, is decreased in mutant RPE cells. Interestingly, our results also indicate a defect in the autophagy process in the Nuc1 RPE, which is probably also linked to impaired lysosomal function, because phagocytosis and autophagy might share common mechanisms in degradation of their targets. ßA3/A1-crystallin is a novel lysosomal protein in RPE, essential for degradation of phagocytosed material.

A Case of Retained Catheter Guidewire Discovered Two Years After Central Venous Catheterization.

BACKGROUND Retained guidewire is a recognized complication of intravascular interventions. The majority of cases are identified immediately or shortly after the procedure. In rare cases, the guidewire is identified incidentally by X-ray after the procedure. This report presents a rare case of a retained venous guidewire that was discovered two years after central venous catheterization. CASE REPORT A 52-year-old African-American man presented with a wire that was emerging from the skin near his right knee. He had undergone a right femoral central venous catheter placement two years previously. Imaging showed that the end of the guidewire was sited at the left pulmonary artery, and was associated with two small broken fragments of wire. During surgery to remove the guidewire, it had become adherent to the pulmonary artery wall. Most of the guidewire was removed, but the portion adherent to the pulmonary artery wall was left in place. CONCLUSIONS It is very rare for a retained guidewire to be discovered when it protrudes through the skin, two years after central venous catheter placement, as the majority of cases are discovered by physical inspection or imaging following intravascular interventions. Skill and attention in the clinical setting are required to minimize such complications.