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1.  Optical Rheology of Porcine Sclera by Birefringence Imaging 
PLoS ONE  2012;7(9):e44026.
To investigate a relationship between birefringence and elasticity of porcine sclera ex vivo using polarization-sensitive optical coherence tomography (PS-OCT).
Elastic parameters and birefringence of 19 porcine eyes were measured. Four pieces of scleral strips which were parallel to the limbus, with a width of 4 mm, were dissected from the optic nerve head to the temporal side of each porcine eye. Birefringence of the sclera was measured with a prototype PS-OCT. The strain and force were measured with a uniaxial material tester as the sample was stretched with a speed of 1.8 mm/min after preconditioning. A derivative of the exponentially-fitted stress-strain curve at 0% strain was extracted as the tangent modulus. Power of exponential stress-strain function was also extracted from the fitting. To consider a net stiffness of sclera, structural stiffness was calculated as a product of tangent modulus and thickness. Correlations between birefringence and these elastic parameters were examined.
Statistically significant correlations between birefringence and all of the elastic parameters were found at 2 central positions. Structural stiffness and power of exponential stress-strain function were correlated with birefringence at the position near the optic nerve head. No correlation was found at the position near the equator.
The evidence of correlations between birefringence and elasticity of sclera tested uniaxially was shown for the first time. This work may become a basis for in vivo measurement of scleral biomechanics using PS-OCT.
PMCID: PMC3435379  PMID: 22970158
2.  Co-localisation of advanced glycation end products and d-β-aspartic acid-containing proteins in gelatinous drop-like corneal dystrophy 
The British Journal of Ophthalmology  2012;96(8):1127-1131.
Gelatinous drop-like corneal dystrophy (GDLD), also known as familial subepithelial corneal amyloidosis, is an autosomal recessive disorder that causes progressive corneal opacity due to accumulation of amyloid fibrils in the corneal stroma. Genetic analyses have revealed that a mutation in membrane component chromosome 1 surface marker 1 gene is responsible for GDLD. However, the mechanism of amyloid formation in the corneal stroma remains unclear. The present study attempted to reveal the role of advanced glycation end products (AGE) and d-amino acids in amyloid formation in GDLD.
Informed consent was obtained from five patients with GDLD, three patients with bullous keratopathy and three patients with interstitial keratitis and all the specimens were analysed. Localisation of amyloid fibrils was analysed using Congo-red and thioflavin T staining. In addition, the localisation of AGE (Nɛ-carboxy(methyl)-l-lysine, pyrraline and pentosidine) and d-β-aspartic acid-containing proteins, a major form of d-amino acid-containing proteins, was analysed immunohistochemically.
In all GDLD specimens, strong immunoreactivity to AGE and d-β-aspartic acid-containing proteins was detected in the subepithelial amyloid-rich region. In contrast, amyloid fibrils, AGE, or d-amino acid-containing proteins were slightly detected in the corneal stroma of patients with bullous keratopathy and interstitial keratitis.
Abnormally accumulated proteins rich in AGE and d-β-aspartic acid co-localise in the amyloid lesions in GDLD. These results indicate that non-enzymatic post-translational modifications of proteins, including AGE formation and isomerisation of aspartyl residues, will be the cause as well as the result of amyloid fibril formations in GDLD.
PMCID: PMC3404710  PMID: 22694960
Advanced glycation end products; biochemistry; cornead-amino acids; d-β-aspartic acid; familial subepithelial corneal amyloidosis; GDLD; gelatinous drop-like corneal dystrophy; M1S1; Nɛ-(carboxy)methyl-l-lysin; optics and refraction; pathology; pentosidine; physiology; pyrraline; treatment surgery; tumour-associated calcium signal transducer 2 (TACSTD2)
3.  Birefringence measurement of cornea and anterior segment by office-based polarization-sensitive optical coherence tomography 
Biomedical Optics Express  2011;2(8):2392-2402.
We present a case series of cornea and anterior segment disorders investigated by an office-based polarization-sensitive optical coherence tomography (PS-OCT). Blebs of glaucoma patients treated by trabeculectomy, and corneas of keratoconus and keratoplasty patients were measured by PS-OCT. Birefringence formations in trabeculectomy bleb were measured in 1 control eye and 3 eyes of trabeculectomy model rabbits. Polarization insensitive scattering OCT and the depth-resolved birefringence were measured simultaneously by PS-OCT. Abnormal birefringence was observed in keratoconus cases with advanced thinning and with a rupture of Descemet’s membrane. The graft-host interface of the keratoplasty case showed abnormal birefringence. The appearance of abnormal birefringence in the cornea was likely to be an indication of cross-linking of collagen fibrils. The measurement of rabbit showed abnormal birefringence in the scarring eyes. Wide regions of strong birefringence were observed in the eyes of trabeculectomy patients who had high intraocular pressure. Visualization of scarring in bleb by PS-OCT may be useful for the planning of secondary surgery. PS-OCT showed promising for the study and diagnosis diseases related to abnormal fibrous tissues of the cornea and anterior eye segment.
PMCID: PMC3149537  PMID: 21833376
(170.1610) Clinical application; (170.2655) Functional monitoring and imaging; (170.3880) Medical and biological imaging; (170.4500) Optical coherence tomography; (170.4460) Ophthalmic optics and devices; (170.4470) Ophthalmology
4.  Carteolol Hydrochloride Suppresses the Generation of Reactive Oxygen Species and Rescues Cell Death After Ultraviolet Irradiation of Cultured Lens Epithelial Cells 
Anti-oxidant activities of adrenergic β-blockers are proposed in various organs. The aim of the present study was to investigate the effect of carteolol hydrochloride, an adrenergic β-blocker, on the production of reactive oxygen species (ROS) and the viable cell number after ultraviolet irradiation of cultured lens epithelial cells (LECs).
Materials and Methodology:
Cultured LECs were exposed to 0, 10–5, 10–4, and 10–3 M carteolol hydrochloride for 30 min followed by ultraviolet B (UVB) irradiation at intensity of 100, 200, or 400 mJ/cm2. The amount of ROS in the LECs was measured using dichlorodihydrofluorescein at 30 min after exposure to UVB. In addition, the number of living LECs was counted at 15 h after exposure to UVB.
Exposure to 10–3 M carteolol hydrochloride significantly decreased the amount of ROS after exposure to UVB at intensities of 100, 200, and 400 mJ/cm2. In addition, 10–3 M carteolol hydrochloride significantly increased the viable cell number after exposure to UVB at 400 mJ/cm2. However, 10–4 and 10–5M carteolol hydrochloride had no significant effect on ROS or the viable cell number in LECs.
Carteolol hydrochloride protects LECs against UVB irradiation by inhibiting the intracellular production of ROS.
PMCID: PMC3031156  PMID: 21283534
Reactive oxygen species; carteolol hydrochloride; ultraviolet; antioxidant; lens epithelial cells.
5.  Psychometric properties of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), Japanese version 
The importance of evaluating the outcomes of health care from the standpoint of the patient is now widely recognized. The purpose of this study is to develop and test a Japanese version of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25).
A Japanese version was developed with a previously standardized method. The questionnaire and optional items were completed by 245 patients with cataracts, glaucoma, or age-related macular degeneration, by 110 others before and after cataract surgery, and by a reference group (n = 31). We computed rates of missing data, measured reproducibility and internal consistency reliability, and tested for convergent and discriminant validity, concurrent validity, known-groups validity, factor structure, and responsiveness to change.
Based on information from the participants, some items were changed to 2-step items (asking if an activity was done, and if it was done, then asking how difficult it was). The near-vision and distance-vision subscales each had 1 item that was endorsed by very few participants, so these items were replaced with items that were optional in the English version. For example, more than 60% of participants did not drive, so the driving question was excluded. Reliability and validity were adequate for all subscales except driving, ocular pain, color vision, and peripheral vision. With cataract surgery, most scores improved by at least 20 points.
With minor modifications from the English version, the Japanese NEI VFQ-25 can give reliable, valid, responsive data on vision-related quality of life, for group-level comparisons or for tracking therapeutic outcomes.
PMCID: PMC1283746  PMID: 16248900
6.  Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis 
Journal of Clinical Investigation  2001;108(1):107-115.
Proximal renal tubular acidosis associated with ocular abnormalities such as band keratopathy, glaucoma, and cataracts is caused by mutations in the Na+-HCO3– cotransporter (NBC-1). However, the mechanism by which NBC-1 inactivation leads to such ocular abnormalities remains to be elucidated. By immunological analysis of human and rat eyes, we demonstrate that both kidney type (kNBC-1) and pancreatic type (pNBC-1) transporters are present in the corneal endothelium, trabecular meshwork, ciliary epithelium, and lens epithelium. In the human lens epithelial (HLE) cells, RT-PCR detected mRNAs of both kNBC-1 and pNBC-1. Although a Na+-HCO3– cotransport activity has not been detected in mammalian lens epithelia, cell pH (pHi) measurements revealed the presence of Cl–-independent, electrogenic Na+-HCO3– cotransport activity in HLE cells. In addition, up to 80% of amiloride-insensitive pHi recovery from acid load in the presence of HCO3–/CO2 was inhibited by adenovirus-mediated transfer of a specific hammerhead ribozyme against NBC-1, consistent with a major role of NBC-1 in overall HCO3– transport by the lens epithelium. These results indicate that the normal transport activity of NBC-1 is indispensable not only for the maintenance of corneal and lenticular transparency but also for the regulation of aqueous humor outflow.
PMCID: PMC209339  PMID: 11435462

Results 1-6 (6)