Microstructural abnormalities in MEWDS demonstrated by ultrahigh resolution optical coherence tomography.

BACKGROUND: Histopathological studies of acute multiple evanescent white dot syndrome (MEWDS) have not been reported because of the transient and benign nature of the disease. Ultrahigh resolution optical coherence tomography (UHR-OCT), capable of high resolution in vivo imaging, offers a unique opportunity to visualize retinal microstructure in the disease. METHODS: UHR-OCT images of the maculae of five patients with MEWDS were obtained and analyzed. Diagnosis was based on clinical presentation, examination, visual field testing, and angiography. RESULTS: UHR-OCT revealed disturbances in the photoreceptor inner/outer segment junction (IS/OS) in each of the five patients (six eyes) with MEWDS. In addition, thinning of the outer nuclear layer was seen in the case of recurrent MEWDS, suggesting that repeated episodes of MEWDS may result in photoreceptor atrophy. CONCLUSIONS: Subtle disruptions of the photoreceptor IS/OS are demonstrated in all eyes affected by MEWDS. UHR-OCT may be a useful adjunct to diagnosis and monitoring of MEWDS.

Effect of Ca2+ on cardiac mitochondrial energy production is modulated by Na+ and H+ dynamics.

The energy production of mitochondria in heart increases during exercise. Several works have suggested that calcium acts at multiple control points to activate net ATP production in what is termed "parallel activation". To study this, a computational model of mitochondrial energy metabolism in the heart has been developed that integrates the Dudycha-Jafri model for the tricarboxylic acid cycle with the Magnus-Keizer model for mitochondrial energy metabolism and calcium dynamics. The model improves upon the previous formulation by including an updated formulation for calcium dynamics, and new descriptions of sodium, hydrogen, phosphate, and ATP balance. To this end, it incorporates new formulations for the calcium uniporter, sodium-calcium exchange, sodium-hydrogen exchange, the F(1)F(0)-ATPase, and potassium-hydrogen exchange. The model simulates a wide range of experimental data, including steady-state and simulated pacing protocols. The model suggests that calcium is a potent activator of net ATP production and that as pacing increases energy production due to calcium goes up almost linearly. Furthermore, it suggests that during an extramitochondrial calcium transient, calcium entry and extrusion cause a transient depolarization that serve to increase NADH production by the tricarboxylic acid cycle and NADH consumption by the respiration driven proton pumps. The model suggests that activation of the F(1)F(0)-ATPase by calcium is essential to increase ATP production. In mitochondria very close to the release sites, the depolarization is more severe causing a temporary loss of ATP production. However, due to the short duration of the depolarization the net ATP production is also increased.

Mitochondrial calcium signaling and energy metabolism.

A computational model of energy metabolism in the mammalian ventricular myocyte is developed to study the effect of cytosolic calcium (Ca(2+)) transients on adenosine triphosphate (ATP) production. The model couples the Jafri-Dudycha model for tricarboxylic acid cycle regulation to a modified version of the Magnus-Keizer model for the mitochondria. The fluxes associated with Ca(2+) uptake and efflux (i.e., the Ca(2+) uniporter and Na(+)-Ca(2+) exchanger) and the F(1)F(0)-ATPase were modified to better model heart mitochondria. Simulations were performed at steady state and with Ca(2+) transients at various pacing frequencies generated by the Rice-Jafri-Winslow model for the guinea pig ventricular myocyte. The effects of the Ca(2+) transients for mitochondria both adjacent to the dyadic space and in the bulk myoplasm were studied. The model shows that Ca(2+) activation of both the tricarboxylic acid cycle and the F(1)F(0)-ATPase are necessary to produce increases in ATP production. The model also shows that in mitochondria located near the subspace, the large Ca(2+) transients can depolarize the mitochondrial membrane potential sufficiently to cause a transient decline in ATP production. However, this transient is of short duration, minimizing its impact on overall ATP production.