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Biomedical subjects

A F Deutman

Publications and source records attributed to A F Deutman.

At least 37 records · Page 2Linked to original sources
PubMed1999

Retinoic acid receptors and retinoid X receptors in the mature retina: subtype determination and cellular distribution.

PURPOSE: In the mature retina retinoic acid (RA) biosynthesis was reported to be regulated by light. RA is of vital importance for proper function of the retina. RA activity is mediated by interaction with nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). The purpose of this study was to determine if and which RARs and RXRs are present in the mature retina, and to determine their location within the retina. METHODS: The reverse transcriptase polymerase chain reaction (RT-PCR) was used to amplify cDNA fragments encoding RARalpha, RARbeta, RARgamma, RXRalpha, RXRbeta, and RXRgamma from human retinal RNA. RT-PCR products were cloned, sequenced, and used in Northern blot experiments. Antibodies directed against each receptor subtype were used for immunocytochemical analysis. RESULTS: RT-PCR and Northern blot analysis indicated that all RAR and RXR subtypes are present in the mature retina. Western blot analysis, using a cytoplasmic protein fraction isolated from the bovine and human neural retina, showed the presence of RXRalpha. Immunocytochemical analysis of the human, bovine, and rat retina showed that RARalpha is highly expressed in the outer segments of cone photoreceptor cells. RXRalpha expression was observed in the rod inner segment layer. RXRgamma was detected in the nuclei and outer segments of cone photoreceptor cells. CONCLUSIONS: The retinal expression pattern of RARs and RXRs is heterogeneous. The observation that RXRalpha is present in rods whereas RARalpha is present in cones, suggests a mechanism by which RA that is produced upon bleaching, could generate different responses in the two photoreceptor cell subtypes.

Animals↗
PubMed1999

The 2588G-->C mutation in the ABCR gene is a mild frequent founder mutation in the Western European population and allows the classification of ABCR mutations in patients with Stargardt disease.

In 40 western European patients with Stargardt disease (STGD), we found 19 novel mutations in the retina-specific ATP-binding cassette transporter (ABCR) gene, illustrating STGD's high allelic heterogeneity. One mutation, 2588G-->C, identified in 15 (37.5%) patients, shows linkage disequilibrium with a rare polymorphism (2828G-->A) in exon 19, suggesting a founder effect. The guanine at position 2588 is part of the 3' splice site of exon 17. Analysis of the lymphoblastoid cell mRNA of two STGD patients with the 2588G-->C mutation shows that the resulting mutant ABCR proteins either lack Gly863 or contain the missense mutation Gly863Ala. We hypothesize that the 2588G-->C alteration is a mild mutation that causes STGD only in combination with a severe ABCR mutation. This is supported in that the accompanying ABCR mutations in at least five of eight STGD patients are null (severe) and that a combination of two mild mutations has not been observed among 68 STGD patients. The 2588G-->C mutation is present in 1 of every 35 western Europeans, a rate higher than that of the most frequent severe autosomal recessive mutation, the cystic fibrosis conductance regulator gene mutation DeltaPhe508. Given an STGD incidence of 1/10,000, homozygosity for the 2588G-->C mutation or compound heterozygosity for this and other mild ABCR mutations probably does not result in an STGD phenotype.

ATP-Binding Cassette Transporters↗
PubMed1998

The visual cycle retinol dehydrogenase: possible involvement in the 9-cis retinoic acid biosynthetic pathway.

The 11-cis-retinol dehydrogenase (11-cis-RoDH) gene encodes the short-chain alcohol dehydrogenase responsible for 11-cis-retinol oxidation in the visual cycle. The structure of the murine 11-cis-RoDH gene was used to reinvestigate its transcription pattern. An 11-cis-RoDH gene transcript was detected in several non-ocular tissues. The question regarding the substrate specificity of the enzyme was therefore addressed. Recombinant 11-cis-RoDH was found capable of oxidizing and reducing 9-cis-, 11-cis- and 13-cis-isomers of retinol and retinaldehyde, respectively. Dodecyl-beta-1-maltoside used to solubilize the enzyme was found to affect the substrate specificity. This is the first report on a visual cycle enzyme also present in non-retinal ocular and non-ocular tissues. A possible role in addition to its role in the visual cycle is being discussed.

Alcohol Oxidoreductases↗
PubMed1998

A randomized controlled clinical trial on the efficacy of radiation therapy in the control of subfoveal choroidal neovascularization in age-related macular degeneration: radiation versus observation.

BACKGROUND: The results of several pilot studies concerning radiation therapy for age-related subfoveal choroidal neovascularization (CNV) have been published recently. Although positive treatment results have been described, it is not known whether this therapy alters the natural course of eyes with neovascular age-related macular degeneration (AMD). A randomized controlled clinical trial was conducted in which radiation therapy was compared with observation in patients with subfoveal neovascular AMD. METHODS: Seventy-four patients with a recent drop in central vision due to subfoveal age-related CNV were randomized to either radiation treatment or observation. Patients with either classic, occult or mixed type CNV were included. Eyes in the treatment group received a radiation dose of 24 Gy in four fractions of 6 Gy. Evaluation of data concerning visual acuity (VA) and fluorescein angiography occurred at 3, 6 and 12 months after inclusion. RESULTS: At 12 months of follow-up 52.2% of the observation group versus 32.0% of the irradiation group had lost 3 or more lines of VA (P = 0.03, log rank test). More severe visual decline, 6 lines or more, was observed in 40.9% of the observation versus 8.8% in the irradiation group (P = 0.002 using log rank test). At 12 months 39.6% of the observation group and 20.0% of the treatment group had VA of less than 0.1 (P = 0.08, log rank test). The size of the CNV membrane doubled in 25.2% of eyes in the observation group versus 20.0% in the treatment group at least 12 months (P = 0.5, log rank test). No side effects were observed. CONCLUSION: Preservation of VA was significantly better in the treatment group compared with the control group at 12 months. Nevertheless we noted a drop in central vision of 3 or more lines in a substantial proportion of the treatment group. Radiation therapy does not prevent visual loss in all patients with age-related subfoveal CNV, and whether the treatment benefit at 12 months will persist has to be awaited.

Aged↗
PubMed1998

Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR.

Ophthalmological and molecular genetic studies were performed in a consanguineous family with individuals showing either retinitis pigmentosa (RP) or cone-rod dystrophy (CRD). Assuming pseudodominant (recessive) inheritance of allelic defects, linkage analysis positioned the causal gene at 1p21-p13 (lod score 4.22), a genomic segment known to harbor the ABCR gene involved in Stargardt's disease (STGD) and age-related macular degeneration (AMD). We completed the exon-intron structure of the ABCR gene and detected a severe homozygous 5[prime] splice site mutation, IVS30+1G->T, in the four RP patients. The five CRD patients in this family are compound heterozygotes for the IVS30+1G->T mutation and a 5[prime] splice site mutation in intron 40 (IVS40+5G->A). Both splice site mutations were found heterozygously in two unrelated STGD patients, but not in 100 control individuals. In these patients the second mutation was either a missense mutation or unknown. Since thus far no STGD patients have been reported to carry two ABCR null alleles and taking into account that the RP phenotype is more severe than the STGD phenotype, we hypothesize that the intron 30 splice site mutation represents a true null allele. Since the intron 30 mutation is found heterozygously in the CRD patients, the IVS40+5G->A mutation probably renders the exon 40 5[prime] splice site partially functional. These results show that mutations in the ABCR gene not only result in STGD and AMD, but can also cause autosomal recessive RP and CRD. Since the heterozygote frequency for ABCR mutations is estimated at 0.02, mutations in ABCR might be an important cause of autosomal recessive and sporadic forms of RP and CRD.

ATP-Binding Cassette Transporters↗
PubMed1997

Cloning and structural analysis of the murine GCN5L1 gene.

We recently cloned the murine 11-cis retinol dehydrogenase gene. A second gene, the murine GCN5L1 gene, was found to be situated upstream of the murine 11-cis retinol dehydrogenase gene. We have isolated and sequenced the complete coding sequence of the murine GCN5L1 gene. The distance between the 3'-end of the murine GCN5L1 gene and the 5'-end of the 11-cis retinol dehydrogenase gene is only 776 nt. The murine GCNSL1 gene consists of four exons encompassing approximately 3.5 kb of genomic DNA. Intron/exon splice sites conform to the GT/AG rule. The open reading frame consists of 375 nucleotides encoding a 14 kDa protein. The murine GCN5L1, like the human GCN5L1 protein, displays weak homology (27%) to yeast GCN5. The distance between the murine, human and bovine GCN5L1 and 11-cis retinol dehydrogenase genes appeared to be conserved.

Alcohol Oxidoreductases↗
PubMed1997

Reticular dystrophy of the retinal pigment epithelium and choroidal neovascularization. A fluorescein and ICGV study.

We report the clinical history of 2 patients affected with reticular dystrophy of the retinal pigment epithelium and central choroidal neovascularization. With time, spontaneous reduction of the subretinal fluid associated with consequent improvement of the visual acuity has been noted in our first case. The second patient showed a stable fibrotic subfoveal choroidal neovascularization. Conventional fluorescein angiography and indocyanine green videoangiography findings are illustrated. The differential diagnosis between other reticular pigmented lesions often associated with choroidal neovascularization is discussed.

Adult↗
PubMed1996

Delay in diagnosis of homocystinuria: retrospective study of consecutive patients.

OBJECTIVE: To assess the causes for delay in the diagnosis of homocystinuria. DESIGN: Clinical and laboratory data were collected from patients diagnosed as having homocystinuria due to cystathionine synthase deficiency, with special reference to the ages at which the patients had their first major signs of the disease, ectopia lentis was established, and homocystinuria was diagnosed. SETTING: University hospital in the Netherlands. SUBJECTS: 34 patients (18 males) in whom homocystinuria due to cystathionine synthase deficiency was diagnosed in the period 1970-94. RESULTS: Among 34 consecutively detected homocystinuria patients the mean age at diagnosis of homocystinuria was 24 (range 1-61) years. Despite frequent ocular manifestations, serious complications in the vascular, skeletal, and central nervous systems, and repeated examinations performed in these patients by clinicians of various disciplines, there was a mean delay of 11 (0-43) years between the first major signs of the disease (at mean age 13 (1-40) years) and the ultimate diagnosis of homocystinuria. Even when ectopia lentis was diagnosed (in 26 (76%) patients, mean age 18 (1-50) years), this did not lead to adequate biochemical analysis for homocystinuria at the time of detection, causing a mean diagnostic delay of 8 (0-24) years in these patients. CONCLUSIONS: Three factors should have precipitated the diagnosis of homocystinuria: early recognition that unusual myopia (high, very high, abnormal progressive, or at young age) was caused by subluxation of the ocular lenses; awareness that the occurrence of myopia combined with systemic complications ("myopia plus") might be due to homocystinuria; and appropriate biochemical investigations carried out in patients with ectopia lentis and in their siblings.

Adolescent↗
PubMed1996

Butterfly-shaped pigment dystrophy of the fovea associated with subretinal neovascularization.

BACKGROUND: The association of butterfly-shaped pigment dystrophy of the fovea, an uncommon inherited macular disease, with subretinal neovascularization has rarely been reported in the literature. CASE REPORT: We describe the clinical history of a patient affected with butterfly-shaped pigment dystrophy of the fovea, myopia, and optic nerve head dysplasia. She was followed up for 23 years. During the course of the disease, bilateral subretinal neovascularization in the macular area occurred. Fluorescein angiography confirmed the diagnosis. Recently, indocyanine green (CG) videoangiography was also performed. Because of the bilateral subfoveal localization no laser treatment was advised. DISCUSSION: Usually, good visual acuity is maintained in this uncommon inherited macular disease. However, acute visual loss can be caused by the ingrowth of subretinal new vessels. Therefore, if visual acuity decreases or metamorphopsia develops in these patients, careful biomicroscopic examination and fluorescein/ICG angiography is advisable.

Angiography↗
PubMed1996

The development of central areolar choroidal dystrophy.

BACKGROUND: Central areolar choroidal dystrophy (CACD) is a hereditary macular disorder of which the development is poorly understood. METHODS: One hundred and eight members of seven families with CACD underwent ophthalmological examination. If macular alterations were found or suspected, the patients underwent fluorescein angiography, electroretinography (ERG), electrooculography (EOG) and tests of colour vision and visual field. CACD was divided into four stages: I, slight parafoveal changes of the pigment epithelium (RPE); II, RPE mottling encircling the fovea; III, additional atrophy of the choriocapillaris without central involvement; IV, as stage III with central involvement. RESULTS: In 60 eyes of 30 patients, 8 with stage I, 12 with stage II, 18 with stage III and 22 with stage IV CACD were found. The photopic ERG was subnormal in about half of the cases with stage II-IV. Colour vision tests revealed diminished red sensitivity and pseudoprotanomaly in stages I and II and combined red-green and blue-yellow defect in stages III and IV. Parafoveal reduced sensitivity (stages I and II) and parafoveal and foveal reduced sensitivity (stages III and IV) were found in the visual field tests. CONCLUSION: We describe and expand the stages of development of CACD. Early recognition of patients may have a great influence on their subsequent life.

Adult↗
PubMed1996

Recurrent intrascleral cyst after strabismus surgery.

BACKGROUND: Intrascleral epithelial inclusion cysts have been described after ocular trauma, scleral buckling and strabismus surgery. They are usually small, asymptomatic and located anteriorly. CASE REPORT: The clinical history of a 9-year-old girl who developed a huge epi- and retrobulbar intrascleral cyst in both the upper and the lower nasal quadrants after multiple strabismus operations is described. RESULTS: Surgical resection of the cyst wall was twice unsuccessful. Drainage of the cyst, followed by the injection of tetracycline (30 mg/ml) in the cyst site, led to complete recovery. CONCLUSION: Recurrent posteriorly located intrascleral cyst can occur after strabismus surgery. Therapy consisting of drainage combined with intrascleral administration of tetracycline solution (30 mg/ml) to induce sclerodesis appeared to be effective during a 2-year follow-up period.

Anti-Bacterial Agents↗
PubMed1996

Genetic fine mapping of the gene for recessive Stargardt disease.

Stargardt disease (STGD) is one of the most frequent causes of macular degeneration in childhood. Linkage analysis in families with recessive STGD has recently shown genetic homogeneity and a location of the underlying gene at 1p22-p21 in a 4-cM interval. Haplotype analysis in seven Dutch STGD families with 11 highly polymorphic markers spanning the critical region has enabled us to refine the location of the underlying gene to a 2-cM region flanked by the loci D1S406 and D1S236. We have identified one 45-year-old nonpenetrant individual who carries two disease alleles. In another family, an affected individual inherited the paternal but not the maternal disease chromosome, suggesting genetic heterogeneity or a different mechanism leading to the disease in this family.

Alleles↗
PubMed1996

Autosomal dominant central areolar choroidal dystrophy caused by a mutation in codon 142 in the peripherin/RDS gene.

PURPOSE: Because several macular dystrophies are caused by mutations in the peripherin/RDS gene, we examined autosomal dominant and sporadic cases of central areolar choroidal dystrophy for mutations in the peripherin/RDS gene. METHODS: DNA sequence analysis of the peripherin/RDS gene was performed in four sporadic cases and in ten affected and nine unaffected individuals from seven families with autosomal dominant central areolar choroidal dystrophy. RESULTS: An Arg-142-Trp mutation in the peripherin/RDS gene was found in ten affected family members in seven families. Among these, a 69-year-old man with the Arg-142-Trp mutation, who was unaffected six years before blood sample analysis, showed a parafoveal area of chorioretinal atrophy. The 65-year-old sister of this family had the Arg-142-Trp mutation with no macular abnormalities, but she might still develop central areolar choroidal dystrophy at an older age. No mutation was found in the four sporadic cases. CONCLUSION: Autosomal dominant central areolar choroidal dystrophy, studied in seven families, is caused by an Arg-142-Trp mutation in the peripherin/RDS gene.

Adult↗
PubMed1996

Central areolar choroidal dystrophy and slowly progressive sensorineural hearing loss.

Central areolar choroidal dystrophy (CACD) is a rare hereditary disorder leading to a central scotoma in middle-aged patients. Two cases of CACD in association with perceptive hearing loss are discussed. A 62-year-old male and a 51-year-old female patient complained of visual deterioration and subsequent hearing loss over several years. In addition to routine ophthalmic and otorhinolaryngological examination both patients underwent fluorescein angiography, (electro)physiological examination and audiometry examination. A demarcated area of atrophy of pigment epithelium and choriocapillaris was found in both patients. A slowly progressive sensorineural hearing loss after adolescence was found in both patients. The hearing deteriorated to such a level at middle age that hearing aids were necessary. These two cases show that CACD may be associated with perceptive hearing loss.

Audiometry↗
PubMed1995

[Results of photorefractive keratectomy using the excimer laser in the treatment of myopia; 1-year follow-up].

OBJECTIVE: Evaluation of the first excimer laser treatments of myopia. DESIGN: Descriptive. SETTING: Excimer Laser Centrum, Department of Ophthalmology, University of Nijmegen, Nijmegen, the Netherlands. METHOD: 312 patients underwent spherical excimer laser treatment to correct myopia of 1.2 up to 10 diopters between February 1992 and October 1993. 245 patients completed a follow-up of one year or more; 36 retreatments were carried out. Group I (treatment 1.2 to 6 D) numbered 174 patients, group II (6.1-10 D) 71 patients. RESULTS: After a follow-up period of one year or just before retreatment 79% of group I and 48% of group II achieved a refractive correction within 1 D of the attempted correction. Visual acuity without correction was 0.5 or more in 94% of group I and in 76% of group II. Less than one percent (n = 1) of group I and 6% (n = 4) of group II lost more than one line of best corrected visual acuity. Retreatment could correct 50% of those eyes that did not achieve a refraction within 1 D of attempted correction. Loss of visual acuity was corrected by retreatment in 5 of 6 cases of group I and in 7 of 11 cases of group II. CONCLUSION: Based on a one-year follow-up, refractive surgery with the excimer laser appears to correct myopia between 1 and 10 D effectively. Predictability is diminishing on correcting higher amounts of refractive error. Thorough information of the patients regarding the results to be expected will prevent disappointment.

Adolescent↗
PubMed1995

Radiation therapy for age-related subfoveal choroidal neovascular membranes. A pilot study.

In this pilot study the effect of radiation therapy on subfoveal CNV membranes associated with age-related macular degeneration was evaluated. Four groups of 10 patients were treated with external beam radiotherapy (16 MV photons) on an area of 1 cm2 (macular region) using a lens-sparing technique and total dose of 8 to 24 Gy. The first group received 8 Gy in a single fraction. In this group only 30% had a stable visual acuity and a stable FA after 18 months follow-up. In 50% of patients in group 2 (12 Gy) and 40% of patients in group 3 (18 Gy) the visual acuity and FA appearance remained stable after 18 months of follow-up. In the last group (24 Gy) 80% of patients had a stable visual acuity and FA appearance after 12 months follow-up. Comparison of these findings with the natural history data of subfoveal age-related CNV, suggests a beneficial effect of radiation therapy with a total dose of 12 Gy or more on the progression of CNV membranes.

Aged↗