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Purpose To investigate extraocular muscle (EOM) path shift and prolapse of posterior eyeball from muscle cone in acquired esotropia with high myopia (AEHM), using magnetic resonance imaging. Design A case-control study. Methods There were 16 eyes with AEHM, 11 with high myopia (HM), 12 with moderate myopia (MM), and 11 control eyes. Extraocular muscle shift was evaluated by measuring angles formed by the line connecting orbital centroids and the line connecting each orbital centroid and each EOM centroid. The ratio of the prolapse in the posterior eyeball from the muscle cone was also measured. Results Both inferior shift of lateral rectus (LR) and nasal shift of superior rectus (SR) muscle were observed in the AEHM group, compared with HM, MM, and control groups. Neither shifted significantly in the HM group compared with control group. The prolapse ratio in AEHM group was higher than in the HM, MM, and control groups. Greater EOM shifts and eyeball prolapse were observed when the AEHM was more severe, as in esotropia fixus. Conclusion In AEHM, a prolapsing eyeball shifts LR inferiorly and SR nasally; these findings were not observed in high myopia with neither ocular deviation nor restriction. These shifts reduce abduction and supraduction and increase infraduction and adduction in AEHM. The shifts would be predicted to create a hypoesodeviation, which is a common finding in AEHM. Both EOM shifts and superotemporal eyeball prolapse tend to be greater in esotropia fixus.

In 524 Japanese individuals with deutan colour vision defect, 76 had a normal-order pigment gene array, where the L gene is at the first position and the M gene(s) is located downstream. Of these 76 individuals, 69 had a -71A>C substitution in the M gene without any other mutation. Because the expression of L/M genes is up-regulated by thyroid hormone (T3) in human retinoblastoma WERI cells, we examined the effects of T3 on promoter activity; T3 increased the activity of the -71A promoter 2-fold, but it had no effect on the -71C promoter. Similarly, the -71C promoter was much less activated by T3 than the -71A promoter in HEK293 cells expressing thyroid hormone receptor isoform β2. Such a weak response of the -71C promoter to T3 may cause a decrease in the number of M cones and/or the density of M pigment during the differentiation of M cones. The average Rayleigh match midpoint was 18.9 ± 4.1 in 162 ordinary deuteranomaly individuals, but was 37.3 ± 9.1 in 63 deuteranomaly individuals with -71C. The -71A>C substitution was found to be specific to eastern Asia. These results suggest that there may be a new subset of deuteranomaly associated with -71C in the Japanese (and probably eastern Asian) population(s).

Deuteranomaly, and to a lesser extent deuteranopia, are associated with a 5′ green-red 3′ (G-R) visual pigment hybrid gene. Such G-R hybrid genes may also exist in males with normal color vision. This discrepancy can be explained if the position of the G-R hybrid gene in the array determines the probability of its expression in the retina. In accord with our previous findings, we confirm that when a G-R hybrid gene occupies the second position in the array, a deutan defect results (N = 2); whereas when a normal green pigment gene does, normal color vision ensues (N = 3). Regarding gene expression as a function of position in the array, in 5 postmortem retinae from individuals whose arrays contained one red and two green pigment genes that differed at a polymorphic site in exon 5, only the green pigment gene that occupied the second position in the array was expressed into retinal mRNA. In conclusion, our data suggest that only the first two genes in the X-chromosome linked visual gene array are expressed in the retina and, therefore, influence the color vision phenotype. Green-red hybrid genes cause deuteranomaly only if they occupy the second position in the array. © 2000 John Wiley & Sons, Inc. Col Res Appl, 26, S79–S83, 2001

Among the 447 Japanese men with deutan color-vision deficiency that we analyzed, 61 had a normal order array of L/M pigment genes. Three of the 61 men had an exonic mutation, but the other 58 had no mutations even in the flanking introns of their M genes. In these 58 men, 55 had a -71A --> C substitution in the M gene. Two hypotheses were built up for the substitution: it is in linkage disequilibrium with a genuine cause of deficiency in the introns, or itself is the cause of the deficiency. For the first hypothesis, we sequenced entire regions of both the L and M genes in 30 color-normal Japanese men who had one each of the L and M genes to understand normal variations of the introns. Fifty-two already known and 15 newly identified polymorphic sites could be classified into three categories: those with no polymorphisms in the Japanese group, those essentially different between the L and the M genes, and the others. We then sequenced the entire region of the M genes in 12 representative deutan individuals with a normal gene-order array but found no significant mutations. For the second hypothesis, we performed a reporter assay and found that the M gene promoter with -71C had a 60-70% reduction in activity when compared to that with -71A. These results suggest that the -71A --> C substitution is not in linkage disequilibrium with an intronic mutation, but the substitution itself may affect the transcription of the M gene, leading to deutan deficiency.

Thirty-nine missense mutations, which had been identified in rod monochromacy or related disorders, in the CNGA3 subunit of cone photoreceptor cGMP-gated channels were analyzed. HEK293 cells were transfected with cDNA of the human CNGA3 subunit harboring each of these mutations in an expression vector. Patch-clamp recordings demonstrated that 32 of the 39 mutants did not show cGMP-activated current, suggesting that these 32 mutations cause a loss of function of the channels. From the remaining 7 mutants that showed cGMP-activated current, two mutations in the cyclic nucleotide-binding domain, T565M or E593K, were further studied. The half-maximal activating concentration (K(1/2)) for cGMP in the homomeric CNGA3-T565M channels (160microM) was 17.8-fold higher than that of the homomeric wild-type CNGA3 channels (9.0microM). Conversely, the K(1/2) for cGMP in the homomeric CNGA3-E593K channels (3.0microM) was 3-fold lower than that of the homomeric wild-type CNGA3 channels. These results suggest that the T565M and E593K mutations alter the apparent affinity for cGMP of the channels to cause cone dysfunction, resulting in rod monochromacy.

The DNAs from 217 Japanese males with congenital red/green color-vision deficiencies were analyzed. Twenty-three subjects had the normal genotype of a single red gene, followed by a green gene. Four of the 23 were from the 69 protan subject group and 19 of the 23 were from the 148 deutan subject group. Three of the 23 subjects had missense mutations. The mutation Asn94Lys (AAC--AAA) occurred in the single green gene of a deutan subject (A155). The Arg330Gln (CGA--CAA) mutation was detected in both green genes of another deutan subject (A164). The Gly338Glu (GGG--GAG) mutation occurred in the single red gene of a protan subject (A89). Both normal and mutant opsins were expressed in cultured COS-7 cells and visual pigments were regenerated with 11-cis-retinal. The normal red and green opsins showed absorbance spectra with lambda(max) of 560 and 530 nm, respectively, but the three mutant opsins had altered spectra. The mutations in Asn94Lys and Gly338Glu resulted in no absorbance and the Arg330Gln mutation gave a low absorbance spectrum with a lambda(max) of 530 nm. Therefore these three mutant opsins are likely to be affected in the folding process, resulting in a loss of function as a visual pigment.

PURPOSE The human cone photoreceptor cyclic nucleotide-gated (CNG) channel comprises alpha- and beta-subunits, which are respectively encoded by hCNGA3 and hCNGB3. The purpose was to examine the functional role of hCNGB3 in modulation of human cone CNG channels and to characterize functional consequences of rod monochromacy-associated mutations in hCNGB3 (S435F and D633G). METHODS Macroscopic patch currents were recorded from human embryonic kidney (HEK) 293 cells expressing homomeric (hCNGA3 and hCNGB3) and heteromeric (hCNGA3/hCNGB3, hCNGA3/hCNGB3-S435F, and hCNGA3/hCNGB3-D633G) channels using inside-out patch-clamp technique. RESULTS Both hCNGA3 homomeric and hCNGA3/hCNGB3 heteromeric channels were activated by cGMP, with half-maximally activating concentration (K(1/2)) of 11.1 +/- 1.0 and 26.2 +/- 1.9 micro M, respectively. The hCNGA3 channels appeared to be more sensitive to inhibition by extracellular Ca(2+) compared with hCNGA3/hCNGB3 channels, when assessed by the degree of outward rectification. Coexpression of either of rod monochromacy-associated mutants of hCNGB3 with hCNGA3 significantly reduced K(1/2) value for cGMP but little affected the sensitivity to extracellular Ca(2+), compared with wild-type heteromeric channels. The selectivity of hCNGA3, hCNGA3/hCNGB3, hCNGA3/hCNGB3-S435F, and hCNGA3/hCNGB3-D633G channels for monovalent cations were largely similar. Immunoprecipitation experiments showed association of hCNGA3 subunit with both of wild-type and mutant hCNGB3 subunits. CONCLUSIONS The hCNGB3 plays an important modulatory role in the function of human cone CNG channels with respect to cGMP and extracellular Ca(2+) sensitivities. The rod monochromacy-associated S435F and D633G mutations in hCNGB3 evokes a significant increase in the apparent affinity for cGMP, which should alter cone function and thereby contribute at least partly to pathogenesis of the disease.

A case of malignant melanoma of the lacrimal sac in a 41-year-old woman is reported, which is propably the 12th one in the world literature. Dacryocystectomy is advisable at a localized stage. The importance of early diagnosis is discussed.

Measurements of Constrast Sensitivity Functions (CSF) were made on normal observers made artificially highly ametropic with spectacle lenses (with high back vertex) distance in order to determine the effect of retinal image size alterations upon CSF measures. While not an exact model for high ametropia per se, this experiment served to familiarize the experimenters with problems associated with the task. Image size alterations occur normally in aphakic patients and highly myopic patients. As a clinical trial, a series of aphakic observers were tested using an interferometric acuity device. CSF measures were made with the patient's spectacle corrections in place and again with correcting contact lenses substituted. The contact lenses reduce induced image size alterations in these cases. The use of contact lenses in such measures allows differentiation between artifactual low frequency fall off in aphakia due to lens effects and possible low frequency fall-off due to other causes.

The Stiles—Crawford effect of the first kind (SCE I), discovered in 1933, represented a major breakthrough in our understanding of retinal physiology and the modern beginning of the science of photoreceptor optics. The current status of knowledge in this area is briefly reviewed. A study is presented of a white adult female observer with aniridia, clear media, only traces of nystagmus, rather good visual acuity, and good fixation. It is shown that this individual exhibits approximate alignment of her photoreceptors with the center of the retinal sphere, clear evidence of side lobes on functions, and surprisingly steep SCE I functions. The implications of these findings are considered.