Torsion of the optic nerve head is a prominent feature of normal-tension glaucoma.

PURPOSE: To compare optic nerve head (ONH) morphology between eyes with normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG). METHODS: Seventy-eight NTG patients and 78 POAG patients matched according to age and axial length were analyzed. Optic nerve head tilt and torsion were identified from cross-sectional images of optical coherence tomography. The degree of horizontal, vertical, and maximum ONH tilt and torsion was compared between NTG and POAG eyes, and additional comparisons were based on the presence of myopia and the location of the visual field defect. Logistic regression analysis was used to determine the factors related to the degree of ONH torsion. RESULTS: Vertical (P = 0.610) and horizontal tilt degree (P = 0.746) did not differ between NTG and POAG eyes. However, torsion degree (P = 0.022) differed significantly between NTG and POAG eyes. Direction of vertical tilt (P = 0.040) and torsion (P < 0.001) showed more prevalent superior tilt and torsion in NTG eyes (21.8% and 33.3%, respectively) compared to POAG eyes (10.3% and 10.3%, respectively). Myopic NTG eyes showed greater torsion degree (P = 0.014) than nonmyopic NTG eyes, which was not observed in the comparison between myopic and nonmyopic POAG eyes. Only NTG eyes showed a significant difference in the degree of maximum tilt (P < 0.001) and torsion (P < 0.001) and the direction of vertical tilt (P < 0.001) and torsion (P = 0.010) by the location of visual field defect. Longer axial length, maximum tilt degree, and diagnosis of NTG were the factors related to the degree of ONH torsion. CONCLUSIONS: Normal-tension glaucoma eyes had a greater ONH torsion compared to POAG eyes with matched axial length. The direction of the ONH tilt and torsion was related to the location of the visual field defect only in NTG eyes.

Retinol-binding site in interphotoreceptor retinoid-binding protein (IRBP): a novel hydrophobic cavity.

PURPOSE: Interphotoreceptor retinoid-binding protein (IRBP) appears to target and protect retinoids during the visual cycle. X-ray crystallographic studies had noted a betabetaalpha-spiral fold shared with crotonases and C-terminal protein transferases. The shallow cleft formed by the fold was assumed to represent the retinol-binding site. However, a second hydrophobic site consisting of a highly restricted cavity was more recently appreciated during in silico ligand-docking studies. In this study, the ligand-binding environment within the second module of Xenopus IRBP (X2IRBP) is defined. METHODS: Pristine recombinant polypeptide corresponding to X2IRBP was expressed in a soluble form and purified to homogeneity without its fusion tag. Phenylalanine was substituted for tryptophan at each of the putative retinol-binding domains (W450F, hydrophobic cavity; W587F, shallow cleft). Binding of 11-cis and all-trans retinol were observed in titrations monitoring retinol fluorescence enhancement, quenching of tryptophan fluorescence, and energy transfer. The effect of oleic acid on retinol binding was also examined. RESULTS: A ligand-binding stoichiometry of approximately 1:1 was observed for 11-cis and all-trans with K(d) in the tens of nanomolar range. The substitution mutants showed little effect on retinol binding in titrations after fluorescence enhancement. However, the W450F and not the W587F mutant showed a markedly reduced capacity for fluorescence quenching for both 11-cis and all-trans retinol. Oleic acid inhibited the binding of 11-cis and all-trans retinol in an apparent noncompetitive manner. CONCLUSIONS: The binding site for 11-cis and all-trans retinol is a novel hydrophobic cavity that is highly restrictive and probably distinct from the long chain fatty acid-binding site.