Macular Degeneration: Moroi SE

Moroi SE, Heckenlively JR. · No affiliation provided · Ophthalmology. · Pubmed #18519068 No free full text.

This publication has no abstract.

West AL, Oren GA, Moroi SE. · Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA. · Am J Ophthalmol. · Pubmed #16386992 No free full text.

Abstract: PURPOSE: To provide a perspective by reviewing the evidence for the role of nutritional supplements and herbal medicines in the common causes of visual impairment. DESIGN: Retrospective literature review. METHODS: Published studies and information found in PubMed, International Bibliographic Information of Dietary Supplements, and selected websites were reviewed for the role of nutritional and herbal medicines in the treatment of age-related macular degeneration, cataract, diabetic retinopathy, and glaucoma. The studies were evaluated systematically for their study design, study population, benefits, risks, biases, and criteria for the categorization of the level of evidence. RESULTS: The available evidence does support the use of certain vitamins and minerals in patients with certain forms of age-related macular degeneration. For cataracts, the available evidence does not support these supplements to prevent or treat cataracts in healthy individuals. For diabetic retinopathy and glaucoma, the available evidence does not support the use of these supplements. In the category of herbal medicines, the available evidence does not support the use of herbal medicines for any of these ocular diseases. CONCLUSION: Because of the widespread use of nutritional supplements and herbal medicines, ophthalmologists should be aware of their use so that they can inform patients properly when the supplements and herbal medicine are being used for eye disease.

Ayyagari R, Mandal MN, Karoukis AJ, Chen L, McLaren NC, Lichter M, Wong DT, Hitchcock PF, Caruso RC, Moroi SE, Maumenee IH, Sieving PA. · Department of Ophthalmology and Visual Sciences, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA. · Invest Ophthalmol Vis Sci. · Pubmed #16123441 links to  free full text

Abstract: PURPOSE: To identify the gene responsible for a complex ocular phenotype of late-onset macular degeneration, long anterior zonules (LAZ), and elevated intraocular pressure (IOP) and to study its expression. METHODS: Ocular examination, visual field, fluorescein angiography, and electrophysiology testing were performed. One affected individual was treated with vitamin A. DNA from 55 family members (UM:H389) was used for linkage, mapping, and mutation analysis. Linkage analysis of macular degeneration and LAZ phenotypes was performed independently. Mutations in candidate genes were screened by sequencing. mRNA expression of CTRP5 and MFRP, which are bicistronic genes, was studied by semiquantitative RT-PCR (qRT-PCR) in various human tissues. CTRP5 expression was also evaluated by in situ hybridization. RESULTS: Affected members had LAZ detectable by the third decade and/or macular degeneration by the fourth to fifth decade. A six-month treatment with vitamin A shortened dark adaptation considerably in one affected member. Both conditions mapped independently with zero recombination to 11q23, with maximum lod scores of 3.31 for macular degeneration and 5.41 for LAZ. The same CTRP5 missense mutation was identified in all affected individuals. Retinal pigment epithelium (RPE) and ciliary epithelium (CE) showed highest CTRP5 transcript expression, which was also true for MFRP. CTRP5 tissue expression was confirmed by in situ hybridization. CONCLUSIONS: A single locus at 11q23 is implicated in a complex ocular phenotype involving RPE and CE, tissues of neuroectodermal origin. All individuals with either LAZ and/or macular degeneration carry the same CTRP5 S163R mutation, which is transmitted in autosomal dominant manner.

Zareparsi S, Buraczynska M, Branham KE, Shah S, Eng D, Li M, Pawar H, Yashar BM, Moroi SE, Lichter PR, Petty HR, Richards JE, Abecasis GR, Elner VM, Swaroop A. · Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA. · Hum Mol Genet. · Pubmed #15829498 links to  free full text

Abstract: Age-related macular degeneration (AMD) is a genetically heterogeneous disease that leads to progressive and irreversible vision loss among the elderly. Inflammation, oxidative damage, cholesterol metabolism and/or impaired function of retinal pigment epithelium (RPE) have been implicated in AMD pathogenesis. We examined toll-like receptor 4 (TLR4) as a candidate gene for AMD susceptibility because: (i) the TLR4 gene is located on chromosome 9q32-33, a region exhibiting evidence of linkage to AMD in three independent reports; (ii) the TLR4-D299G variant is associated with reduced risk of atherosclerosis, a chronic inflammatory disease with subendothelial accumulation; (iii) the TLR4 is not only a key mediator of proinflammatory signaling pathways but also linked to regulation of cholesterol efflux and (iv) the TLR4 participates in phagocytosis of photoreceptor outer segments by the RPE. We examined D299G and T399I variants of TLR4 in a sample of 667 unrelated AMD patients and 439 unrelated controls, all of Caucasian ancestry. Multiple logistic regression demonstrated an increased risk of AMD in carriers of the G allele at TLR4 residue 299 (odds ratio=2.65, P=0.025), but lack of an independent effect by T399I variant. TLR4-D299G showed an additive effect on AMD risk (odds ratio=4.13, P=0.002) with allelic variants of apolipoprotein E (APOE) and ATP-binding cassette transporter-1 (ABCA1), two genes involved in cholesterol efflux. Interestingly, the effect of TLR4, APOE and ABCA1 variants on AMD susceptibility was opposite to that of association with atherosclerosis risk. Our data provide evidence of a link between multiple diverse mechanisms underlying AMD pathogenesis.

Ayyagari R, Griesinger IB, Bingham E, Lark KK, Moroi SE, Sieving PA. · W.K. Kellogg Eye Center, University of Michigan, Ann Arbor 48105, USA. · Arch Ophthalmol. · Pubmed #10636420 links to  free full text

Abstract: OBJECTIVE: To describe the ophthalmic and genetic findings of a large kindred (UM:H389) with autosomal dominant hemorrhagic macular dystrophy. METHODS: The disease state of family members was documented by dilated fundus examination, electroretinography, color vision tests, fluorescein angiography, measurement of visual fields, biomicroscopy, gonioscopy, and intraocular pressure measurement. Linkage and haplo-type analyses were carried out with markers flanking the Sorsby fundus dystrophy TIMP3 (tissue inhibitor of metalloproteinase 3) gene locus, and mutation analysis was carried out by screening exon 5 of the TIMP3 gene. RESULTS: This 4-generation pedigree with autosomal dominant hemorrhagic macular degeneration has visual symptoms beginning in the sixth decade of life. Several family members developed choroidal neovascular membrane formation in the macula of both eyes. The phenotype overlaps that of Sorsby fundus dystrophy. Some of the affected members have unusual zonularlike radial striations on the anterior lens capsule surface, and glaucoma or ocular hypertension has developed in 2 of them. Involvement of the TIMP3 gene was excluded by linkage, haplotype, and mutation analyses. CONCLUSIONS: The phenotype of this family with autosomal dominant macular dystrophy overlaps that of Sorsby fundus dystrophy. Exclusion of the TIMP3 gene in this family indicates genetic heterogeneity for hemorrhagic macular dystrophy. Anterior segment anomalies may occur with this condition, but cosegregation has not yet been established. CLINICAL RELEVANCE: This study broadens the spectrum of hemorrhagic macular dystrophy by identifying a family in which the TIMP3 gene is not involved. Once the gene is cloned, we are eager to learn whether this gene may be involved in age-related macular degeneration.

Moroi SE, Gottfredsdottir MS, Schteingart MT, Elner SG, Lee CM, Schertzer RM, Abrams GW, Johnson MW. · W.K. Kellogg Eye Center, University of Michigan Medical Center, Ann Arbor 48105, USA. · Ophthalmology. · Pubmed #10328408 No free full text.

Abstract: OBJECTIVE: To identify coexisting ocular diagnoses in a case series of eyes that developed cystoid macular edema (CME) associated with latanoprost therapy. DESIGN: Retrospective observational case series. PARTICIPANTS: Seven eyes of seven patients who developed CME possibly associated with latanoprost treatment were studied. INTERVENTION: When these patients, all of whom were treated with latanoprost in addition to other glaucoma medications, described blurred vision or eye irritation, ocular examination revealed CME, which was confirmed by fluorescein angiography. Latanoprost was discontinued, and in three cases topical corticosteroids and nonsteroidal anti-inflammatory agents were used to treat the CME. MAIN OUTCOME MEASURES: Visual acuity and intraocular pressure were determined before latanoprost use began, during therapy, and after latanoprost use ceased. In these cases, resolution of CME was documented clinically after discontinuing latanoprost. RESULTS: Clinically significant CME developed after 1 to 11 months of latanoprost treatment, with an average decrease of 3 lines in Snellen visual acuity. Intraocular pressure decreased an average of 27.9% during treatment. Cystoid macular edema was confirmed in all cases by fluorescein angiography. In these seven patients, the following coexisting ocular conditions may have placed these eyes at risk for prostaglandin-mediated blood-retinal barrier vascular insufficiency: history of dipivefrin-associated CME, epiretinal membrane, complicated cataract surgery, history of macular edema associated with branch retinal vein occlusion, history of anterior uveitis, and diabetes mellitus. In all cases, the macular edema resolved following discontinuation of latanoprost, in some instances with concomitant use of steroidal and nonsteroidal anti-inflammatory agents. CONCLUSIONS: In this case series of pseudophakic, aphakic, or phakic eyes, the temporal relationships between the use of latanoprost and developing CME, and the resolution of CME following cessation of the drug, suggest an association between latanoprost and CME. In all cases, coexisting ocular conditions associated with an altered blood-retinal barrier were present.