Retinal disease in the C3 glomerulopathies and the risk of impaired vision.

BACKGROUND: Dense deposit disease and atypical hemolytic uremic syndrome are often caused by Complement Factor H (CFH) mutations. This study describes the retinal abnormalities in dense deposit disease and, for the first time, atypical haemolytic uremic syndrome. It also reviews our understanding of drusen pathogenesis and their relevance for glomerular disease. METHODS: Six individuals with dense deposit disease and one with atypical haemolytic uremic syndrome were studied from 2 to 40 years after presentation. Five had renal transplants. All four who had genetic testing had CFH mutations. Individuals underwent ophthalmological review and retinal photography, and in some cases, optical coherence tomography, and further tests of retinal function. RESULTS: All subjects with dense deposit disease had impaired night vision and retinal drusen or whitish-yellow deposits. Retinal atrophy, pigmentation, and hemorrhage were common. In late disease, peripheral vision was restricted, central vision was distorted, and there were scotoma from sub-retinal choroidal neovascular membranes and atypical serous retinopathy. Drusen were present but less prominent in the young person with atypical uremic syndrome due to a heterozygous CFH mutation. CONCLUSIONS: Drusen are common in forms of C3 glomerulopathy caused by compound heterozygous or heterozygous CFH mutations. They are useful diagnostically but also impair vision. Drusen have an identical composition to glomerular deposits. They are also identical to the drusen of age-related macular degeneration, and may respond to the same treatments. Individuals with a C3 glomerulopathy should be assessed ophthalmologically at diagnosis, and monitored regularly for vision-threatening complications.

Trifluoroacetylsulfenyl trifluoroacetate, CF(3)C(O)-S-O-C(O)CF(3), a novel compound with a symmetrically substituted S-O bond: synthesis, spectroscopic characterization, and quantum chemical calculations.

The new compound trifluoroacetylsulfenyl trifluoroacetate, CF(3)C(O)SOC(O)CF(3), which possesses two identical carbonyl substituents attached to the S-O bond, has been synthesized. The IR and UV spectra of the gas phase as well as the (13)C NMR spectrum of the solution in CDCl(3) were recorded and assigned. Quantum chemical calculations were performed with the ab initio methods HF and MP2 and the density functional approach B3LYP. The 6-31G basis set was chosen in all calculations. The molecule possesses a skew structure, and according to all computational methods, the syn-syn structure (C=O bonds of both C(O)CF(3) groups synperiplanar to S-O bond) represents the most stable conformer. In agreement with the quantum chemical calculations, the presence of small amounts (< or =5%) of a second conformer (anti-syn) cannot be excluded on the basis of the IR spectrum. The calculated values for the torsional angle around the S-O bond (delta(C-S-O-C)) of the syn-syn form are smaller than 80 degrees (72-78 degrees). Comparison with theoretical results for the corresponding disulfide CF(3)C(O)SSC(O)CF(3) and peroxide CF(3)C(O)OOC(O)CF(3) indicates that the structural properties of sulfenyl compounds are more similar to those of disulfides than to those of peroxides.

Gas-phase structures of acetyl peroxynitrate and trifluoroacetyl peroxynitrate.

The molecular structures and conformational properties of acetyl peroxynitrate (PAN, CH3C(O)OONO2) and trifluoroacetyl peroxynitrate (FPAN, CF3C(O)OONO2) were investigated in the gas phase by electron diffraction (GED), microwave spectroscopy (MW), and quantum chemical methods (HF/3-21G, HF/6-31G*, MP2/6-31G*, B3PW91/6-31G*, and B3PW91/6-311+G*). All experimental and theoretical methods show the syn conformer (C=O bond of acetyl group syn to O-O bond) to be strongly predominant relative to the anti conformer. The O-NO2 bonds are extremely long, 1.492(7) A in PAN and 1.526(10) A in FPAN, which correlates with their low bond energy and the easy formation of CX3C(O)OO* and *NO2 radicals in the atmosphere. The O-O bonds (1.418(12) A in PAN and 1.408(8) A in FPAN) are shorter than that in hydrogen peroxide (1.464 A). In both compounds the C-O-O-N dihedral angle is close to 85 degrees.

Tautomers and conformers of malonamide, NH2-C(O)-CH2-C(O)-NH2: vibrational analysis, NMR spectra and ab initio calculations.

The conformational and tautomeric compositions of malonamide, NH2-C(O)-CH2-C(O)-NH2 were determined by vibrational spectroscopy and theoretical calculations (HF/6-31G*, B3PW91/6-31G*). Solid state Fourier transform infrared and Raman spectra were analysed. They reveal the existence of a diketo tautomer. Theoretical calculations predict a diketo structure belonging to the C1 symmetry group. No enol form is present in the molecule in the solid. 13C-NMR studies show only signals of a diketo tautomer.

A search for a mammalian homologue of the Drosophila photoreceptor development gene glass yields Zfp64, a zinc finger encoding gene which maps to the distal end of mouse chromosome 2.

Whilst searching for a mammalian homologue of the Drosophila glass gene we cloned a mouse cDNA whose deduced sequence encodes a 614 amino acid (aa) protein with ten Cys2-His2 (C2H2) zinc finger (Zf) motifs. Zfp64 is expressed in all developing and mature mouse tissues examined, except the mouse erythroleukemia (MEL) cell line. Zfp64 maps to the distal region of mouse chromosome 2 close to lens opacity 4 (Lop4), a semidominant cataract mutation. Sequence analysis shows that Zfp64 has multiple potential phosphorylation sites for casein kinase II (CK II), protein kinase C (PKC), tyrosine kinase (TK) and c-AMP- and c-GMP-dependent protein kinase (cA/GMPDPK).

Isolated metastases to the retina or optic nerve.

Isolated metastases to the retina or optic nerve are extremely rare. Retinal metastases arise from cutaneous malignant melanoma and carcinomas (lung, gastrointestinal, genitourinary, and breast). Most patients present with reduced vision. The clinical appearance of these metastases is variable. Melanoma metastases are brown or black, whereas carcinoma metastases are white. Frequently, retinal hemorrhages and exudates are seen. Optic nerve metastases arise from carcinomas (lung, breast, and gastrointestinal) in adults and acute leukemias in children. As is true of retinal metastases, most patients present with reduced vision. Though in most cases there is a visible optic nerve mass, some patients have optic disc edema only. Investigations are directed by a known history of malignancy in many patients and by physical examination. Cytological workup of vitreous may be required. Treatment options include observation, radiotherapy in eyes with visual potential, and enucleation for pain control. The visual prognosis is poor. In patients with retinal or optic nerve metastases, median survival is approximately 9 months after the onset of visual symptoms, but is slightly longer in cases in which the primary lesion is breast carcinoma.

Delayed choroidal perfusion in giant cell arteritis.

The fundus fluorescein angiograms of 13 patients with visual disturbance due to biopsy-proven giant cell arteritis (11 with anterior ischemic optic neuropathy (AION); 2 with visual obscurations only) were compared with the fluorescein angiograms from 33 patients with acute nonarteritic AION and 23 age-matched normal eyes. In all 13 patients with giant cell arteritis, the fluorescein angiograms showed a significant delay of choroidal filling time (mean 69 seconds) in comparison with either normal subjects (mean 5.8 seconds) or patients with nonarteritic AION (mean 5.5 seconds). In patients presenting with acute AION, the finding of delayed choroidal filling on fluorescein angiography should raise the index of suspicion of giant cell arteritis and lead to prompt investigation and treatment.