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Masami Kojima

Publications and source records attributed to Masami Kojima.

50 records · Page 3Linked to original sources

Lens and cataract research of the 20th century: a review of results, errors and misunderstandings.

Lens and cataract research from a clinical, biophysical, biological and mainly biochemical point of view has a long tradition. Already since the beginning of the 20th century research relating to the chemical composition and metabolism of the lens was conducted. With these analyses an attempt was made to understand the existence and maintenance of lens transparency and the mechanisms leading to lens opacities. Around the middle of the century the stationary analyses measuring the content of certain substances in the lens were more and more replaced by the search for dynamic metabolic processes responsible for lens growth, maintenance of transparency and possibly active participation in lens function (such as accommodation). Also the disturbances as a result of ageing or the formation of lens opacities have been investigated and resulted partially in the elucidation of reaction chains, leading from a trigger to the formation of a cataract. Lens biochemistry is no longer a closed book to us, but there are still many question marks. Why were we not able to solve more problems around lens and cataract? The research effort with a remarkable financial input and a great number of scientists worldwide during the second half of the century does not correspond to the results obtained. There must be something wrong with our strategy, our interpretation of the results or even both. We would like to stress some points which might be regarded as errors or misunderstandings in the lens research community, thus preventing a better outcome of the enormous investment of work and money. A great disadvantage is the missing cooperation between clinicians and epidemiologists on one hand and basic lens researchers on the other. Especially the ignorance of basic researchers regarding the clinical problems of the lens and of cataracts might be to blame for several 'errors and misunderstandings'. It is not even so long ago since the slitlamp microscope examination of animals belonged to the essential standard methods of a lens research team. Another disadvantage still is the use of the general diagnosis 'cataract' by the clinicians without further classification of the topography of the opacification, which supports the concept that all cataracts have the same trigger mechanism. But most regrettable is the fact that many clinicians have never been really interested in basic research of the lens, in cataract pathogenesis and epidemiology of risk factors or in testing the efficacy of cataract-preventing medication. Their main goal was cataract surgery. On the basis of the success of the cataract surgery at the present time clinicians have even developed the opinion that lens and cataract research is no longer necessary to overcome cataract blindness. But as we all know this refers only to highly industrialized countries; millions of cataract-blind people are still without such help and a change of this condition is not in sight. In our opinion lens and cataract research is still necessary and it will be more successful if we bear in mind the mostly unintentional errors of the 20th century but keep them out of our daily practice.

Animals↗

Risk factors for nuclear lens opacification: the Reykjavik Eye Study.

PURPOSE: The purpose of this study is to examine risk factors for nuclear lens opacification in citizens of Reykjavik. METHODS: 1,045 persons, 583 females and 462 males aged 50 years and older, were randomly sampled and underwent a detailed eye examination and answered a questionnaire. In all Scheimpflug photography of the anterior eye segment was done including the lens as well as retroilluminated photography of the lens. These photographs were used for the diagnosis of lens opacification. The data was analyzed using a logistic regression model. RESULTS: An increased risk for all grades of nuclear opacifications was found with ageing (OR = 1.228, 95% CI = 1.192-1.264, p = 0.000), cigarette smoking for more than 20 pack/years (OR = 2.521, 95% CI = 1.521-4.125, p = 0.000) and pipe or cigar smoking (OR = 2.478, 95% CI = 1.200-5.116, p = 0.014). Outdoor exposure, cortical lens opacification grade II and III and computer usage were not found to be linked to higher risk of nuclear opacification. No correlation was found between nuclear opacification and the consumption of vitamins, herring, sardines and shrimps, cod-liver oil or plant oil, nor were iris color, hyperopia, systemic steroid use, cardiovascular disease, diabetes, glaucoma and pseudoexfoliation found to have a significant effect. CONCLUSIONS: Ageing is a major risk factor for nuclear lens opacification, and smoking is a major modifiable risk factor. Cortical and nuclear lens opacifications do not share the same modifiable risk factors.

Aged↗

High prevalence of nuclear cataract in the population of tropical and subtropical areas.

The authors have conducted cataract epidemiological studies in four climatically and racially different places and compared the data. The survey places were Noto and Amami in Japan, Reykjavik in Iceland, and Singapore. The evaluation and grading of lens opacities were done using graphic analysis of Scheimpflug and retro-illumination images. The prevalence of nuclear opacity was extremely high in the Singapore group, followed by Amami. The main type of lens opacity was nuclear in the Singapore group and cortical in the Noto and Icelandic groups. The characteristic lens opacity in Amami was in between the above two groups. No significant difference was seen in the prevalence of nuclear opacity between males and females in any of the groups. Although the common factors of the living conditions in the subjects with a high prevalence of nuclear opacity appear to be high UV exposure and high ambient temperature, future investigations should be made to disclose the possible cause.

Aged↗

The effects of protective eyewear on glare and crystalline lens transparency.

PURPOSE: Sunglasses have generally been used to protect against glare. Various kinds of sunglasses which correspond to the visual environment are on the market (e.g. for driving, fishing, skiing, etc.). As for the spectral transmission factor of sunglasses, the differences that occur in user's eyes with aging have not been fully considered. We investigated the relationship between different levels of crystalline lens transparence and the effects of glare protection using two kinds of filters. SUBJECTS AND METHODS: A Tri-Blocker filter (TB) and general driving filter (ActiveDrive, ADR) were used. The TB absorbs three spectral wavelengths (below 400 nm, blue light, 575 nm) and can be transparent for other visible light. The ADR reduces the light below 650 nm. TB and ADR transmit 52.5 and 29.0% of the visible light, respectively. Twenty-five normal volunteers with transparent lenses (n = 48 eyes, aged from 22 to 68 years) and 10 cortical cataract patients (n = 18 eyes, aged from 48 to 71 years) were selected. The visual acuity of all subjects was 1.0 or better with the best correction. Contrast sensitivity function (CSF) was measured in four simulated light conditions (daylight, daylight with peripheral glare, twilight, twilight with central glare) by MCT8000 (Vistech). The light scattering intensity of the crystalline lens was measured by EAS-1000 (Nidek). RESULTS: The TB improved the CSF of the elderly volunteers under daylight conditions and of 1 of the cataract patients under all conditions. In the younger group, the CSF did not change under daylight conditions and deteriorated under twilight conditions. Although the ADR was effective for glare protection in the young volunteers, the protective effects of the TB were better than those of ADR for the middle-aged group. CONCLUSION: Sunglasses not only protect against glare but also stabilize visual quality under various light conditions (e.g. passing through a tunnel while driving). Aging changes in lens transparency should be specially considered when developing protective eyewear.

Adult↗

Environmental temperature and cataract progression in experimental rat cataract models.

PURPOSE: To clarify whether or not ambient temperature relates to cataract development or the progression of cataract formation. MATERIALS AND METHODS: 36 Brown Norway rats were divided into two groups, a high-temperature (35 +/- 2 degrees C, H = high) breeding group and a regular-temperature (24 +/- 2 degrees C, L = low) group. Each group was further divided into an experimentally induced diabetic cataract subgroup (50 mg/kg streptozotocin, DM), an ultraviolet B exposure-induced cataract subgroup (200 mJ/cm2, UV), and a normal control subgroup (C = control). Slit-lamp microscopy and an anterior image analysis system (EAS-1000) were used to evaluate lens changes. RESULTS: Both the HC and HUV groups in the 35 degrees C conditions showed higher light scattering than that of the 24 degrees C conditions (LC and LUV) 3 weeks after the start of the experiment. Nine weeks after the start of the experiment, all the rats of the UV subgroups (HUV and LUV) developed anterior subcapsular cataract. The temperature did not have much influence on the progression of the UV-B-induced cataract. From 18 days after the start of the experiment, the HC subgroup showed a wider light scattering area than the LC. An increase in abnormal nuclear scattering light in the crystalline lens of group HC was found in 9 weeks after the start of the experiment, and at the end of the experiment (78 weeks later), dense abnormal nuclear light scattering was found including the prenuclear area. In contrast, the HDM group in the 35 degrees C conditions showed slower cataract progression than that of the LDM group at 24 degrees C room temperature. CONCLUSIONS: Although further experiments are necessary before we can draw any conclusions about temperature and nuclear changes, paying attention to the effects of temperature on the lens is worthwhile.

Animals↗

Reductions in bone mass, structure, and strength in axial and appendicular skeletons associated with increased turnover after ovariectomy in mature cynomolgus monkeys and preventive effects of clodronate.

Over 16 months, we evaluated the effects of ovariectomy (OVX) and bisphosphonate clodronate (CLO) on bone in 48 cynomolgus monkeys (9-15 years old) fed a normal calcium diet. We established three OVX groups (oral CLO at 0 [OVX control], 12, or 60 mg/kg per day) and one sham-operated (SHAM) group. At 16 months, the bone mineral density (BMD) values (percentage of group baseline; OVX control vs. SHAM) for lumbar bone (L3-L5), proximal femur, midfemur, radius, and tibia were -2.6% versus 11.2%, -3.5% versus 8.9%, -3.0% versus 9.0%, -5.5% versus 15.7%, and -6.7% versus 13.9%, respectively. In OVX control (i) tibia showed significant loss of bone mineral content (BMC; vs. baseline), (ii) urinary deoxypyridinoline (DPD) and serum osteocalcin (OC) levels increased (peak = 182% and 168%, respectively, of SHAM), (iii) in lumbar bone and midfemur, ultimate load (UL) was reduced (vs. SHAM), (iv) in lumbar bone, trabecular bone-formation rates (BFRs) were not changed significantly, but tibial endocortical and intracortical bone formation rates were significantly raised (vs. SHAM), (v) the volumetric BMD (vBMD) and geometry of the tibial cortex (measured by peripheral quantitative computed tomography [pQCT]) were significantly reduced (vs. SHAM). CLO, 60 mg/kg per day but not 12 mg/kg per day, significantly inhibited OVX-induced changes, age-dependent increases in bone mass, and ability to maintain structure. Thus, in OVX mature cynomolgus monkeys (possibly, a unique model of the cortical bone loss secondary to estrogen deficiency), the post-OVX increases in systemic bone markers were slight, but stimulation of local turnover in the cortical envelope was enough to cause bone loss (more so in tibia than in lumbar trabecular bone). High-dose CLO prevented these changes.

Amino Acids↗

Low vitamin E level as a subliminal risk factor in a rat model of prednisolone-induced cataract.

PURPOSE: To investigate the relationship between vitamin E deficiency and prednisolone-induced cataract formation, long-term examination of lens changes was performed in rats under the condition of vitamin E deficiency or supplementation and administration of prednisolone. METHODS: Rats were divided into six groups: normal chow (N), vitamin E-deficient chow (ED), normal chow with prednisolone instillation (NP), vitamin E-deficient chow with prednisolone instillation (EDP), NP treatment with vitamin E supplementation (NP+VE), and EDP treatment with vitamin E supplementation (EDP+VE). Prednisolone (1 mg/kg small middle dot d) and vitamin E (5%; 10 microL per administration per eye, 1 mg/kg small middle dot d) were applied in the cul-de-sac. Lens changes were documented and analyzed. Vitamin E status was confirmed by measuring peroxide-induced hemolysis. RESULTS: After 15 months, 91.7% of the eyes in the EDP group showed development of anterior and posterior cortical cataracts. Supplementation with vitamin E significantly reduced cataract formation (to 38.9% of eyes). Neither a vitamin E-deficient diet nor prednisolone treatment alone significantly increased cataract formation. Hemolysis-susceptibility tests confirmed the expected vitamin E status of rats fed vitamin E-deficient chow and rats supplemented with eye drops containing vitamin E. CONCLUSIONS: Vitamin E deficiency and long-term prednisolone treatment together cause cataracts. Singly, however, both conditions are subliminal cataractogenic risk factors.

Animals↗

[Risk factors for lens opacification in Icelanders 50 years and older. Reykjavík Eye Study.].

OBJECTIVE: To examine risk factors for cortical and nuclear lens opacification in older citizens of Reykjavík. MATERIAL AND METHODS: 1045 persons, 583 females and 462 males age 50 years and older were randomly sampled and underwent detailed eye examination including slit-lamp and Scheimpflug photography of the lens and answered a questionnaire. The photographs were used for the diagnosis of lens opacification. The data was analysed using a logistic regression model. RESULTS: An increased risk was found with ageing for developing both nuclear (OR=1.23: 95% CI 1.19-1.26: p<.001) and severe cortical lens opacification (OR=1.19: 95% CI 1.16-1.22: p<.001). Cigarette-smoking for more than 20 pack-years increased risk for nuclear lens opacification (OR=2.52: 95% CI 1.52-4.13: p<.001) as well as pipe- or cigar-smoking (OR=2.48: 95% CI 1.20-5.12: p<.05). Those who spent more than 4 hours/day outside on weekdays in their 20's - 30's and 40's and 50's were found to have increased risk of severe cortical lens opacification (OR=2.80: 95% CI 1.01-7.80: p<.05 and OR=2.91: 95% CI 1.13-9.62: p<.05, respectively). Systemic corticosteroid use was also found to be a significant risk factor for cortical lens opacification (OR=3.70: 95% CI 1.43-9.56: p<.05). CONCLUSION: In our study, ageing is the main risk factor for both cortical and nuclear lens opacification. Important modifiable risk factors are smoking for nuclear lens opacification and systemic corticosteroid use and outdoor exposure for cortical lens opacification.

English Abstract↗

Effect of KAD-1229, a novel hypoglycaemic agent, on plasma glucose levels after meal load in type 2 diabetic rats.

1. The effects of KAD-1229 (a novel non-sulphonylurea agent), voglibose (an alpha-glucosidase inhibitor) and nateglinide (a non-sulphonylurea antihyperglycaemic agent) on hyperglycaemia induced by a meal load were assessed in diabetic rats. 2. KAD-1229 suppressed the increase in plasma glucose levels seen after a meal load and the area under the curve for plasma glucose levels (AUCglucose) up to 5 h after the meal load. 3. Voglibose also suppressed the increase in plasma glucose levels; however, a significant decrease in AUCglucose following voglibose was not observed. 4. Nateglinide suppressed the increase in plasma glucose levels at 30 min and 1 h after the meal load; however, plasma glucose levels was above control thereafter and the AUCglucose was not decreased. 5. The results indicate that KAD-1229 has an antihyperglycaemic effect and KAD-1229 is suggested to be a suitable agent for controlling post-prandial hyperglycaemia.

Animals↗

Oxcarbazepine antinociception in animals with inflammatory pain or painful diabetic neuropathy.

1. Diabetic neuropathy is one of the most frequent complications of diabetes mellitus. However, the mechanisms underlying these disorders are not yet well defined and it has been reported that currently available analgesics have hardly any ameliorating effect on painful diabetic neuropathy. 2. The purpose of the present study was to evaluate the antinociceptive effect of oxcarbazepine (OCBZ), a keto derivative of carbamazepine (CBZ), in animal models generally used in pain research and in rats and mice with streptozotocin (STZ)-induced diabetes. In addition, we compared the effect of OCBZ with those of CBZ, mexiletine and morphine. 3. Diabetes was induced by injection of STZ at a dose of 300 mg/kg (i.p.) in mice and 50 mg/kg (i.v.) in rats. Experiments were conducted 2 weeks after STZ injection and those animals with a serum glucose level above 400 mg/dL were used for data analysis. Antinociceptive effects of the drugs were evaluated by the paw withdrawal test (normal, STZ-induced diabetic and carrageenin-injected rats), tail-flick test (normal and STZ-induced diabetic mice) and nociceptive behaviour (formalin-injected mice). 4. In the present study, diabetic mice showed thermal hyperalgesia and diabetic rats exhibited mechanical hyperalgesia. From these results, the STZ-induced diabetic animals used in the present study were found to be suitable for research on painful diabetic neuropathy. In STZ-induced diabetic animals, the antinociceptive effects of OCBZ, CBZ and mexiletine were facilitated, whereas the effect of morphine was attenuated, compared with effects in normal animals. 5. Oxcarbazepine inhibited the formalin-induced biphasic pain responses and increased the nociceptive threshold in the case of carrageenin-induced hyperalgesia. In view of these results, inhibition of substance P-mediated pain transmission may be involved in the antinociceptive action of OCBZ. 6. These results indicate that OCBZ has an analgesic action and is a possible therapeutic agent for the treatment of neuropathic pain, such as occurs in painful diabetic neuropathy.

Analgesics↗

Prevalence of primary cornea guttata and morphology of corneal endothelium in aging Japanese and Singaporean subjects.

The purpose of the present study was to examine, in the aging people, racial and gender differences in the morphology of corneal endothelium as well as the incidence of cornea guttata in two Asian subject groups, one in Singapore and the other in Japan. Four hundred and sixty-five Chinese Singaporeans and 299 Japanese subjects (residents of Monzen-machi, Ishikawa Prefecture) aged 50 years and older were recruited for the study. Corneal endothelial abnormalities were diagnosed with slit-lamp biomicroscopy and specular microscopy. Primary cornea guttata appeared as beaten metal appearance in slit-lamp images and dark regions in specular images. In addition to cornea guttata, corneal endothelial morphology was also analysed with specular microscopy. The mean cell density was 2,808/mm(2) in the Japanese subjects which was significantly higher than the 2,718/mm(2) seen in the Singaporeans (p < 0.001). The incidence of cornea guttata was significantly higher in the Singaporeans than in the Japanese individuals and also higher in women than in men of both racial groups. These differences support not only a racial and a gender factor but also a possible environmental influence.

Cell Count↗

An alternative method of steroid-induced lens opacification in brown norway rat eyes applying systemic pulse administration.

PURPOSE: To confirm whether long-term administration of prednisolone sodium succinate (prednisolone) alone is able to induce cataract in rat eyes. MATERIALS AND METHODS: A 1% solution of prednisolone was administered topically as eye drops to Brown Norway rat eyes, and a systemic pulse administration of 10 mg/kg/day was given via the tail vein. Both administration methods were applied in different combinations. Eighty-three 6-week-old male rats were divided into 8 groups: group 1 = control; group 2 = topical instillation every day; group 3 = single pulse; group 4 = single pulse + eye drops; group 5 = 3 times pulse; group 6 = 3 times pulse + eye drops; group 7 = 3 times pulse per 2 months; group 8 = 3 times pulse per 2 months + eye drops. Observations for changes of lens transparency were made by slitlamp microscopy and documented by an anterior eye segment analysis system (Nidek EAS-1000) from the onset of drug administration to a maximum period of 16 months. RESULTS: Lens opacity in the shallow anterior and posterior lens layers developed from the tenth month following commencement of prednisolone administration. The incidence of anterior and/or posterior cortical cataract at the sixteenth month was 15% in group 2, 12.5% in group 5, 25% in group 6, 17.9% in group 7 and 35.3% in group 8. The lenses of groups 1, 3 and 4 maintained their transparency throughout the observation period. Light scattering intensity in groups 8 and 7 was the highest, followed by groups 6 and 5, then groups 2, 4, 3 and 1. CONCLUSION: Cortical cataract was successfully induced in Brown Norway rat eyes by sustained administration of prednisolone succinate alone applied as systemic pulse.

Animals↗

Ultraviolet B-induced corneal and lens damage in guinea pigs on low-ascorbic acid diet.

To evaluate ocular morphological response to ultraviolet B (UV-B) exposure in guinea pigs fed with normal and low-ascorbic acid (ASA) diets, 24 guinea pigs were randomly divided into UVR (normal diet + UV-B), LVC (low-ASA diet + UV-B) and CTL (normal diet, without UV-B) groups. The irradiated animals were exposed to 8.2 J/cm(2) of UV-B over 29 weeks. Changes in the cornea and lens were examined using a Scheimpflug camera, specular microscope and histological studies. ASA contents in the plasma, aqueous humor and lens sections were measured by high-performance liquid chromatography. The results showed low contents of ASA in the plasma, aqueous humor and lens sections in LVC. Both irradiated groups displayed corneal epithelial edema, neovascularization in stroma, increase in corneal thickness, decrease in endothelial density, and lens epithelial damage. No significant morphological differences in cornea and lens were found between guinea pigs fed with low-ASA or normal diet.

Animals↗

Racial differences of lens transparency properties with aging and prevalence of age-related cataract applying a WHO classification system.

PURPOSE: To investigate racial differences of lens transparency properties and the prevalence of lens opacification by age. METHODS: Lenses of randomly selected Asian (1,038 Japanese and 517 Singaporeans) and Caucasian (1,045 Icelanders) subjects were evaluated for their lens transparency property (LTP). The prevalence of lens opacification was determined with a newly proposed WHO cataract classification system. RESULTS: LTP increased with aging for all nationalities. Light scattering intensity was significantly higher in the Singaporeans followed by the Icelandic subjects. The prevalence of cortical opacification in Singaporeans was significantly higher than those of the other nationalities up to the age of 60, and the prevalence in Asians was significantly higher than that in Caucasians aged 60-69. Cortical opacification was more prevalent than the other types for both Japanese and Icelanders in their 50s, 60s and 70s. Regarding the central optical zone, the prevalence in the Singaporeans was significantly higher than in the other two groups in their 50s and 60s. The prevalence of nuclear opacification in Singaporeans was markedly higher than those of the two other groups for all ages. Subcapsular cataract was the least prevalent type for all age groups and nationalities; however, the highest prevalence was observed in Singaporeans. CONCLUSIONS: Lens transparency decreased with age in the Singaporeans more markedly than in the other two groups. The high prevalence of nuclear opacification in Singaporeans is considered to be due to environmental rather than race-specific factors.

Aged↗