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Biomedical subjects

M Seeliger

Publications and source records attributed to M Seeliger.

13 recordsLinked to original sources
PubMed2006

Hypoxic preconditioning and erythropoietin protect retinal neurons from degeneration.

Reduced tissue oxygenation stabilizes the alpha-subunit of the transcription factor hypoxia-inducible factor-1 (HIF-1). This leads to the induction of a number of hypoxia responsive genes. One of the best known HIF-1 targets is erythropoietin that exerts neuroprotective effects on ischemia-related injury in the brain. Thus, pre-exposure to low environmental oxygen concentrations might be exploited as a preconditioning procedure to protect tissues against a variety of harmful conditions. We present recent work on neuroprotection of retinal photoreceptors induced by hypoxic preconditioning or by systemically elevated levels of Epo in mouse plasma.

Animals↗
PubMed2001

[Vitamin A metabolism and retinal degeneration].

Vitamin A plays an important role in the pathogenesis and during the course of retinal degenerations. Following a brief overview of the metabolic pathway of Vitamin A from the entrance into the body to the arrival in retinal target structures, the most important retinal degenerations that are related to the Vitamin A-metabolism are presented. Ways of prevention or therapy of such diseases are discussed in the light of the still incomplete knowledge about basic mechanisms of retinol transport and metabolism.

Humans↗
PubMed2001

Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.

Usher syndrome type I (USH1) is an autosomal recessive disorder characterized by congenital sensorineural hearing loss, vestibular dysfunction and visual impairment due to early onset retinitis pigmentosa (RP). So far, six loci (USH1A-USH1F) have been mapped, but only two USH1 genes have been identified: MYO7A for USH1B and the gene encoding harmonin for USH1C. We identified a Cuban pedigree linked to the locus for Usher syndrome type 1D (MIM 601067) within the q2 region of chromosome 10). Affected individuals present with congenital deafness and a highly variable degree of retinal degeneration. Using a positional candidate approach, we identified a new member of the cadherin gene superfamily, CDH23. It encodes a protein of 3,354 amino acids with a single transmembrane domain and 27 cadherin repeats. In the Cuban family, we detected two different mutations: a severe course of the retinal disease was observed in individuals homozygous for what is probably a truncating splice-site mutation (c.4488G-->C), whereas mild RP is present in individuals carrying the homozygous missense mutation R1746Q. A variable expression of the retinal phenotype was seen in patients with a combination of both mutations. In addition, we identified two mutations, Delta M1281 and IVS51+5G-->A, in a German USH1 patient. Our data show that different mutations in CDH23 result in USH1D with a variable retinal phenotype. In an accompanying paper, it is shown that mutations in the mouse ortholog cause disorganization of inner ear stereocilia and deafness in the waltzer mouse.

Alternative Splicing↗
PubMed2000

Oa1 knock-out: new insights on the pathogenesis of ocular albinism type 1.

Ocular albinism type I (OA1) is an X-linked disorder characterized by severe reduction of visual acuity, strabismus, photophobia and nystagmus. Ophthalmologic examination reveals hypopigmentation of the retina, foveal hypoplasia and iris translucency. Microscopic examination of both retinal pigment epithelium (RPE) and skin melanocytes shows the presence of large pigment granules called giant melanosomes or macromelanosomes. In this study, we have generated and characterized Oa1-deficient mice by gene targeting (KO). The KO males are viable, fertile and phenotypically indistinguishable from the wild-type littermates. Ophthalmologic examination shows hypopigmentation of the ocular fundus in mutant animals compared with wild-type. Analysis of the retinofugal pathway reveals a reduction in the size of the uncrossed pathway, demonstrating a misrouting of the optic fibres at the chiasm, as observed in OA1 patients. Microscopic examination of the RPE shows the presence of giant melanosomes comparable with those described in OA1 patients. Ultrastructural analysis of the RPE cells, suggests that the giant melanosomes may form by abnormal growth of single melanosomes, rather than the fusion of several, shedding light on the pathogenesis of ocular albinism.

Albinism, Ocular↗
PubMed1999

Selective loss of cone function in mice lacking the cyclic nucleotide-gated channel CNG3.

Two types of photoreceptors, rods and cones, coexist in the vertebrate retina. An in-depth analysis of the retinal circuitry that transmits rod and cone signals has been hampered by the presence of intimate physical and functional connections between rod and cone pathways. By deleting the cyclic nucleotide-gated channel CNG3 we have generated a mouse lacking any cone-mediated photoresponse. In contrast, the rod pathway is completely intact in CNG3-deficient mice. The functional loss of cone function correlates with a progressive degeneration of cone photoreceptors but not of other retinal cell types. CNG3-deficient mice provide an animal model to dissect unequivocally the contribution of rod and cone pathways for normal retinal function.

Animals↗
PubMed1999

Comparative study of visual, auditory, and olfactory function in Usher syndrome.

BACKGROUND: Usher syndrome is a genotypically and phenotypically heterogeneous group of autosomal recessive diseases featuring retinitis pigmentosa (RP) and sensorineural hearing loss. A general ciliary dysfunction has been suspected following reports of a mutated cytoskeletal protein (myosin VIIA) in type IB, and preliminary data has suggested an olfactory deficit. The purpose of this study was to quantitatively assess olfactory function in Usher syndrome patients and to search for a correlation between the degree of impairment of the three sensory systems as indication of an underlying ciliary defect. METHODS: 39 patients with Usher syndrome (8 type I, 31 type II) were examined. The ophthalmologic protocol included patient history, visual acuity, eye morphology, Goldmann perimetry, and electroretinography. The ENT protocol included a thorough examination, speech-recognition test, pure-tone audiometry and an olfactory function test. RESULTS: In both groups, visual acuity was typically 20/40, the remaining visual field area was small, and the ERG responses were low to non-detectable. Average hearing loss was 100% in type I and 40% in type II. Olfactory thresholds were normal [median 9.7 (I) and 8.5 (II) vs. 8.5 in the control group]. There were multiple significant correlations between parameters of the same organ, but no relationship between parameters of different sensory systems. CONCLUSION: Almost all Usher syndrome patients in this study had an advanced form of RP. In contrast, auditory function differed considerably between type I and type II. An impairment of the olfactory system could not be detected, and there was no correlation between parameters representing visual function, hearing ability, and olfactory sense.

Adult↗
PubMed1998

Multifocal electroretinography in retinitis pigmentosa.

PURPOSE: To investigate the diagnostic potential of multifocal electroretinography for the evaluation of retinal affection by retinitis pigmentosa in a clinical setting. METHODS: For this prospective study, multifocal electroretinograms were obtained from 38 patients who matched the inclusion criteria of either a detectable photopic Ganzfeld response or visual fields of 10 degrees or more, and from 30 normal volunteers. Recordings were performed with the visual evoked response imaging system, using a resolution of 61 hexagonal elements within a 30-degree visual field. The results of the left eye of each patient and control subject were used for statistical evaluation by the Mann-Whitney U test. RESULTS: The 38 eligible patients included those with Usher syndrome types I and II (one patient and six patients, respectively) and those with autosomal-recessive (18), X-recessive (two), and autosomal-dominant (11) forms of retinitis pigmentosa. In 27 (71%) of these 38 patients, at least a central response of the multifocal electroretinogram was detectable. Loss of multifocal electroretinogram response density in patients with retinitis pigmentosa was significant (P < .00001) in all five eccentricity groups (concentric rings), with a progression from center to periphery. Implicit time was significantly elevated in the third eccentricity group (P < .0038) and increased further toward the periphery (P < .00001). The results did not differ notably between retinitis pigmentosa subgroups. CONCLUSIONS: Because the multifocal electroretinogram differentiates between affected and nonaffected retinal areas, eccentricity-dependent changes in both amplitude and implicit time were found. It can therefore add to the diagnostic information of many patients with retinitis pigmentosa.

Adolescent↗
PubMed1998

Spatial cone activity distribution in diseases of the posterior pole determined by multifocal electroretinography.

Thirty patients with a reduced central vision due to diseases of the posterior pole were examined with the VERIS system developed by Sutter and Tran (Vis Res 1992;32:433-446) to characterize the topography of electroretinographic (ERG) changes in comparison to the results in 30 normal volunteers. Diagnoses included Stargardt's macular dystrophy (SMD, n = 10), age-related macular degeneration (AMD, n = 5), cone dystrophy (CD, n = 5), central retinal vein occlusion (CRVO, n = 5), and autosomal dominant optic atrophy (ADOA, n = 5). The 61 local responses obtained from each subjects were grouped by eccentricity to form five concentric rings. The foveal ERG, originating from a central area of 2 degrees radius, was non-recordable or markedly diminished in all patients except those with optic atrophy, where amplitudes were found to be in the normal range. In patients with advanced stages of SMD, functional defects were larger and involved more peripheral areas than in patients with early stages of SMD or with AMD. A reduction of response amplitude even in the most peripheral ring (17-30.5 degrees eccentricity) was found in cone dystrophies and--moderately--in patients with advanced SMD and central retinal vein occlusion only. Prolonged implicit times were found in all but the patients in early stages of SMD and they were maximal in patients with CRVO. This study shows that the multifocal ERG (MFERG) can contribute to differential diagnosis of retinal diseases of the posterior pole especially in cases with a normal photopic Ganzfeld ERG.

Adult↗
PubMed1997

[Juvenile neuronal ceroid lipofuscinosis (Batten-Mayou) disease. Ophthalmologic diagnosis and findings].

BACKGROUND: Juvenile neuronal ceroid lipofuscinosis (JNCL) is important to the ophthalmologist, since eye symptoms are usually the first evidence of the disease and permit establishment of an early diagnosis. The disorder usually begins with a dramatic loss of vision between age 4 and 10 due to bulls-eye maculopathy followed by rapid degeneration of the retina and pigment epithelium. Blindness results within 1 to 3 years after onset of symptoms. The further course of the disease is mainly determined by degradation of the CNS with motor and intellectual deficits. Most patients die before the age of 30. METHODS: A case of two sisters is presented to demonstrate eye findings and diagnostic procedures, emphasizing electrophysiologic and morphologic tests (peripheral blood smear, histology). RESULTS: Both sisters reported the first decrease in vision at the ages of 8 and 6 respectively; visual acuity at time of visit was light projection (20/400). Both had tapetoretinal degeneration with optic disc atrophy, narrowed vessels, pigment epitheliopathy and bullseye maculopathy. The ERG was almost extinguished in the older sister and greatly reduced in the younger one (scotopic more than photopic). Histologically, vacuolated lymphocytes were found in the peripheral blood smear, as were intracellular inclusions of the fingerprint and curvilinear type in the conjunctival biopsy. CONCLUSION: During the course of JNCL, it is very common for the vision to be affected at the age of 6-7. The correct diagnosis, however, is often made years later when massive neurologic symptoms such as seizures appear. When there is sudden loss of vision in a child of this age combined with a tapetoretinal degeneration, a biopsy or at least a peripheral blood smear should be performed.

Biopsy↗