Occult macular dystrophy (OMD) is an inherited macular dystrophy characterized by progressive loss of macular function but normal ophthalmoscopic appearance. Typical OMD is characterized by a central cone dysfunction leading to a loss of vision despite normal ophthalmoscopic appearance, normal fluorescein angiography, and normal full-field electroretinogram (ERGs), but the amplitudes of the focal macular ERGs and multifocal ERGs are significantly reduced at the central retina. Linkage analysis of two OMD families was performed by the SNP High Throughput Linkage analysis system (SNP HiTLink), localizing the disease locus to chromosome 8p22-p23. Among the 128 genes in the linkage region, 22 genes were expressed in the retina, and four candidate genes were selected. No mutations were found in the first three candidate genes, methionine sulfoxide reductase A (MSRA), GATA binding 4 (GATA4), and pericentriolar material 1 (PCM1). However, amino acid substitution of p.Arg45Trp in retinitis pigmentosa 1-like 1 (RP1L1) was found in three OMD families and p.Trp960Arg in a remaining OMD family. These two mutations were detected in all affected individuals but in none of the 876 controls. Immunohistochemistry of RP1L1 in the retina section of cynomolgus monkey revealed expression in the rod and cone photoreceptor, supporting a role of RP1L1 in the photoreceptors that, when disrupted by mutation, leads to OMD. Identification of RP1L1 mutations as causative for OMD has potentially broader implications for understanding the differential cone photoreceptor functions in the fovea and the peripheral retina.

The abnormalities in the multifocal electroretinograms and optical coherence tomography observed in the OMD patients of different durations strongly support the contribution of RP1L1 mutation to the presence of this disease.

TES of the retina can improve retinal function in eyes with long-standing RAOs.

1 The brain constituents b-phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain (`catecholaminergic/serotoninergic activity enhancer, CAE/SAE, e ect'). (7)Deprenyl (Selegiline) and (7)1-phenyl-2-propylaminopentane [(7)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property. 2 By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (7)1-(benzofuran-2-yl)-2-propylaminopentane [(7)BPAP] was selected as a potential follower of (7)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain. 3 (7)BPAP signi®cantly enhanced in 0.18 mmol 1 71 concentration the impulse propagation mediated release of [ 3 H]-noradrenaline and [ 3 H]-dopamine and in 36 nmol 1 71 concentration the release of [ 3 H]-serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced signi®cantly in the presence of 10 712 ± 10 714 M (7)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic e ect of b-amyloid in 10 714 M concentration. In rats (7)BPAP signi®cantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 mg kg 71 s.c. In the shuttle box, (7)BPAP in rats was about 130 times more potent than (7)deprenyl in antagonizing tetrabenazine induced inhibition of performance.

Multifocal VEPs summed within four quadrants can be used for an objective evaluation of the visual fields. The testing can be obtained in 4 min with no pain or discomfort to the patient.

We examined the effect of FPF-1070 (Cerebrolysin) on neurite outgrowth in explant cultures of dorsal root ganglia (DRG), sympathetic trunks (ST), and ciliary ganglia (CG) from 10- to 11-day chicken embryos. FPF-1070 significantly promoted neurite outgrowth in DRG and ST neurons at all concentrations examined, in comparison with phosphate buffered saline-treated negative controls; however, this effect on neurite outgrowth was not as significant as that observed for nerve growth factor-treated positive controls on DRG and ST neurons. Additionally, FPF-1070 exhibited an inverted U relationship between concentration and effectiveness in DRG and ST neurons. In contrast, FPF-1070 did not affect neurite outgrowth in CG neurons although ciliary neurotrophic factor-treated positive controls showed striking neurite outgrowth. Our results demonstrate that FPF-1070 has different neurotrophic effects depending on the subpopulation of neurons. This study clarifies a role for neurotrophic activity in the mechanism of action of FPF-1070.

The optic discs at the atrophic stage of LHON eyes have glaucoma-like morphological changes. However, the cups were significantly deeper in NTG than LHON. The similarity in the optic disc findings in LHON and NTG suggests that alterations in mitochondrial function may be related to optic disc excavations.

The participation of cytochrome P-450 (CYP) isoforms in the metabolism of selegiline was investigated. Experiments using recombinant CYP isoforms expressed in human lymphoblastoid cells showed CYP2B6 to be the major CYP isoform involved with the metabolism of selegiline. CYP1A2 and CYP3A4 also contributed to the metabolism of selegiline but their catalytic activities were much less than that of CYP2B6. CYP2B6 had a higher affinity for both N-depropagylation (K(m)=21.4 microM) and N-demethylation (K(m)=25.2 microM) of selegiline than CYP3A4 and CYP1A2. In immunoinhibition studies using mixed human hepatic microsomes, selegiline N-depropagylation activity was most strongly inhibited by anti-CYP2B and anti-CYP3A antibodies, while selegiline N-demethylation activity was most inhibited by anti-CYP2B antibody. In CYP2B6-rich human hepatic microsomes, anti-CYP2B antibody had the strongest inhibitory effects on both activities. Selegiline inhibited CYP2B6-mediated (S)-mephenytoin N-demethylation activity and CYP2C19-mediated (S)-mephenytoin 4'-hydroxylation activity. These findings suggest that attention should be paid to the drug-drug interaction associated with CYP2B6 and CYP2C19. In conclusion, CYP2B6 participates in the metabolism of selegiline but the degree of its contribution varies with the level of its expression in human liver.