- Email: [email protected]
Genetic bases of total colourblindness among the Pingelapese islanders. Sudin OH,∗1 Yang YM, Li Y, Zhu D, Hurd JN, Mitchell TN, Silva ED, Maumenee IH. Nat Gen 2000;25:289–293.
Nagar, Madurai 625 020, Tamil Nadu, India. E-mail: aravind@ compuserve.com
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Corneal structure and sensitivity in type 1 diabetes mellitus. Rosenberg ME,* Tervo TMT, Immonen IJ, Mu¨ller LJ, Gro¨nhagen–Riska C, Vesaluoma MH. Invest Ophthalmol Vis Sci 2000;41:2915–2921.
S
INCE CORNEAL WOUND HEALING IS IMPAIRED IN THE
diabetic cornea, the authors examined patients with type 1 diabetes mellitus for changes in corneal morphology and to correlate corneal sensitivity, subbasal nerve morphology, and degree of polyneuropathy with each other. Forty-four eyes of 23 patients with diabetes and nine control eyes were included. Corneal sensitivity was tested with a Cochet–Bonnet esthesiometer, and corneal morphology and epithelial and corneal thickness were determined by in vivo confocal microscopy. The density of subbasal nerves was evaluated by calculating the number of long subbasal nerve fiber bundles per confocal microscopic field. The degree of polyneuropathy was evaluated using the clinical part of the Michigan Neuropathy Screening Instrument classification, and retinopathy was evaluated using fundus photographs. A reduction of long nerve fiber bundles per image was noted to have occurred already in patients with mild to moderate neuropathy, but corneal mechanical sensitivity was reduced only in patients with severe neuropathy. Compared with control subjects the corneal thickness was increased in patients with diabetes without neuropathy. The epithelium of patients with diabetes with severe neuropathy was significantly thinner than that of patients with diabetes without neuropathy. Confocal microscopy appears to allow early detection of beginning neuropathy, because decreases in nerve fiber bundle counts precede impairment of corneal sensitivity. Apparently, the cornea becomes thicker in a relatively early stage of diabetes but does not further change with the degree of neuropathy. A reduction in neurotrophic stimuli in severe neuropathy may induce a thin epithelium that may lead to recurrent erosions.—Thomas J. Liesegang. *Department of Ophthalmology, University of Helsinki, PO Box 220, FIN-00029 HUS, Finland. E-mail: [email protected]
● Genetic bases of total colourblindness among the Pingelapese islanders. Sudin OH,* Yang YM, Li Y, Zhu D, Hurd JN, Mitchell TN, Silva ED, Maumenee IH. Nat Gen 2000;25:289 –293.
C
OMPLETE ACHROMATOPSIA IS A RARE, AUTOSOMAL
recessive-disorder characterized by photophobia, decreased vision, nystagmus and total inability to distinguish colors. Previous work has identified an achromatopsia gene on 2q11 to be CNGA3, the alpha subunit of the cone VOL. 130, NO. 6
photoreceptor cGMP-gated cation channel. The authors of this article studied an isolated population on the Pingelap atoll in Micronesia. Typhoon Lengkieki in approximately 1775 and a subsequent famine affected that population, leaving only a handful of survivors. Now, nearly 10% of the Pinglapese population have achromatopsia and about 30% are carriers. The ancestry of most of these achromats can be traced back to a single male survivor. A second locus for achromatopsia, 8q21-q22, was localized in Pingelapese achromats in 1999. The authors of this study narrowed the achromatopsia locus to 1.4 cM and showed that it segregated with a missense mutation at a highly conserved site in CNGB3, the gene that codes for the beta subunit of the cone cyclic nucleotide-gated cation channel. The Pingelapese achromats are homozygous for a missense mutation in a highly conserved membrane-spanning domain. The authors also identified other mutations in non-Pingelapese achromats. This is an example of using an isolated population to study human genetic disease.— Hans E. Grossniklaus *Laboratory of Developmental Genetics, Johns Hopkins University School of Medicine, Baltimore, MD. E-mail: [email protected]
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Crystal structure of rhodopsin: a G protein-coupled receptor. Palczewski K,* Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Trong IL, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M. Science 2000;289:739 –745.
S
EVEN-HELIX TRANSMEMBRANE RECEPTORS ARE SIGNAL
detectors that activate heterotrimeric GTP-binding proteins (G proteins) in response to extracellular stimuli. These receptors (GPCRs) transmit signals specific for each extracellular stimulus across the membrane lipid bilayer by selectively activating different G proteins. Palczewski and co-workers report the first 3D structure of a GPCR, rhodopsin, at 2.8-angstrom resolution. The highly organized structure in the extracellular region includes a conserved disulfide-bridge and forms the bases for the arrangement of the seven-helix transmembrane motif. The inactivated chromophore, 11-cis retinal, holds the transmembrane region of the protein in the inactive conformation. Interactions of the chromophore with a cluster of residues determine the wavelength of the maximum absorption. Changes in these interactions among rhodopsins facilitate color discrimination. New insights gained from the molecular structure of rhodopsin will help investigators understand how GPCRs transduce signals.— Hans E. Grossniklaus *Department of Ophthalmology, University of Washington, Seattle, WA 98195. E-mail: [email protected]
ABSTRACTS
865
●
Corneal structure and sensitivity in type 1 diabetes mellitus. Rosenberg ME,* Tervo TMT, Immonen IJ, Mu¨ller LJ, Gro¨nhagen–Riska C, Vesaluoma MH. Invest Ophthalmol Vis Sci 2000;41:2915–2921.
S
INCE CORNEAL WOUND HEALING IS IMPAIRED IN THE
diabetic cornea, the authors examined patients with type 1 diabetes mellitus for changes in corneal morphology and to correlate corneal sensitivity, subbasal nerve morphology, and degree of polyneuropathy with each other. Forty-four eyes of 23 patients with diabetes and nine control eyes were included. Corneal sensitivity was tested with a Cochet–Bonnet esthesiometer, and corneal morphology and epithelial and corneal thickness were determined by in vivo confocal microscopy. The density of subbasal nerves was evaluated by calculating the number of long subbasal nerve fiber bundles per confocal microscopic field. The degree of polyneuropathy was evaluated using the clinical part of the Michigan Neuropathy Screening Instrument classification, and retinopathy was evaluated using fundus photographs. A reduction of long nerve fiber bundles per image was noted to have occurred already in patients with mild to moderate neuropathy, but corneal mechanical sensitivity was reduced only in patients with severe neuropathy. Compared with control subjects the corneal thickness was increased in patients with diabetes without neuropathy. The epithelium of patients with diabetes with severe neuropathy was significantly thinner than that of patients with diabetes without neuropathy. Confocal microscopy appears to allow early detection of beginning neuropathy, because decreases in nerve fiber bundle counts precede impairment of corneal sensitivity. Apparently, the cornea becomes thicker in a relatively early stage of diabetes but does not further change with the degree of neuropathy. A reduction in neurotrophic stimuli in severe neuropathy may induce a thin epithelium that may lead to recurrent erosions.—Thomas J. Liesegang. *Department of Ophthalmology, University of Helsinki, PO Box 220, FIN-00029 HUS, Finland. E-mail: [email protected]
● Genetic bases of total colourblindness among the Pingelapese islanders. Sudin OH,* Yang YM, Li Y, Zhu D, Hurd JN, Mitchell TN, Silva ED, Maumenee IH. Nat Gen 2000;25:289 –293.
C
OMPLETE ACHROMATOPSIA IS A RARE, AUTOSOMAL
recessive-disorder characterized by photophobia, decreased vision, nystagmus and total inability to distinguish colors. Previous work has identified an achromatopsia gene on 2q11 to be CNGA3, the alpha subunit of the cone VOL. 130, NO. 6
photoreceptor cGMP-gated cation channel. The authors of this article studied an isolated population on the Pingelap atoll in Micronesia. Typhoon Lengkieki in approximately 1775 and a subsequent famine affected that population, leaving only a handful of survivors. Now, nearly 10% of the Pinglapese population have achromatopsia and about 30% are carriers. The ancestry of most of these achromats can be traced back to a single male survivor. A second locus for achromatopsia, 8q21-q22, was localized in Pingelapese achromats in 1999. The authors of this study narrowed the achromatopsia locus to 1.4 cM and showed that it segregated with a missense mutation at a highly conserved site in CNGB3, the gene that codes for the beta subunit of the cone cyclic nucleotide-gated cation channel. The Pingelapese achromats are homozygous for a missense mutation in a highly conserved membrane-spanning domain. The authors also identified other mutations in non-Pingelapese achromats. This is an example of using an isolated population to study human genetic disease.— Hans E. Grossniklaus *Laboratory of Developmental Genetics, Johns Hopkins University School of Medicine, Baltimore, MD. E-mail: [email protected]
●
Crystal structure of rhodopsin: a G protein-coupled receptor. Palczewski K,* Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Trong IL, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M. Science 2000;289:739 –745.
S
EVEN-HELIX TRANSMEMBRANE RECEPTORS ARE SIGNAL
detectors that activate heterotrimeric GTP-binding proteins (G proteins) in response to extracellular stimuli. These receptors (GPCRs) transmit signals specific for each extracellular stimulus across the membrane lipid bilayer by selectively activating different G proteins. Palczewski and co-workers report the first 3D structure of a GPCR, rhodopsin, at 2.8-angstrom resolution. The highly organized structure in the extracellular region includes a conserved disulfide-bridge and forms the bases for the arrangement of the seven-helix transmembrane motif. The inactivated chromophore, 11-cis retinal, holds the transmembrane region of the protein in the inactive conformation. Interactions of the chromophore with a cluster of residues determine the wavelength of the maximum absorption. Changes in these interactions among rhodopsins facilitate color discrimination. New insights gained from the molecular structure of rhodopsin will help investigators understand how GPCRs transduce signals.— Hans E. Grossniklaus *Department of Ophthalmology, University of Washington, Seattle, WA 98195. E-mail: [email protected]
ABSTRACTS
865