Tsugio Amemiya

Immunohistochemical localization of basic fibroblast growth factor, platelet derived growth factor, transforming growth factor-β and tumor necrosis factor-α in the pterygium

Summary Some fibroangiogenic factors have recently been shown to play potential roles in fibrovascular diseases. The aim of this study was to examine whether there is any relationship between growth factors and pterygium genesis. Twenty-three primary pterygia and 4 normal conjunctiva specimens were analyzed by indirect immunohistochemistry using specific antibodies against basic fibroblast growth factor (b-FGF), platelet derived growth factor (PDGF), transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α). Positive immunostaining of these growth factors was located in the epithelial cells, endothelial cells of vessels, basement membranes of vessels and epithelium, fibroblasts and infiltrating inflammatory cells in the pterygium. In the normal conjunctiva, positive immunolabeling for TGF-β and PDGF was much weaker than in the pterygiurn. We conclude that growth factors may interact directly or indirectly in the pathogenesis of pterygium although proof of this awaits further studies.

Growth factors in cultured pterygium fibroblasts : immunohistochemical and ELISA analysis

Abstract · Background: In order to study growth factors in the pathogenesis and recurrence of pterygium, we grew pterygium tissues in culture and compared fibroblasts from primary and from recurrent pterygia with reference to the fibroangiogenic growth factors basic fibroblast growth factor (b-FGF), platelet-derived growth factor (PDGF), transforming growth factor β (TGF-β) and tumor necrosis factor α (TNF-α). · Methods: We used indirect immunohistochemical procedures against human b-FGF, PDGF, TGF-β and TNF-α. As controls, we used cultured normal human conjunctival fibroblasts. A serum-free conditioned medium (CM) from confluent fibroblasts derived from primary and recurrent explants was assessed by enzyme-linked immunosorbent assay to determine the level of the above-mentioned growth factors. · Results: Immunoreactivity of b-FGF was stronger in recurrent than in primary pterygium fibroblasts. PDGF immunolabeling was stronger in primary than in recurrent pterygium fibroblasts. TGF-β and TNF-α immunolabeling was weak in both pterygia. All these growth factors were very sparse in normal conjunctival fibroblasts. Basic-FGF and TGF-β1 were found in the CM from both primary and recurrent pterygium, while PDGF and TNF-α were not detectable. · Conclusion: The strong immunoreactivity and the release of b-FGF in cultured fibroblasts of recurrent pterygia suggest that fibroblasts may play an important role in the recurrence of pterygium.

Terson syndrome: A case report suggesting the mechanism of vitreous hemorrhage

OBJECTIVE To present a patient with Terson syndrome and to propose a mechanism for vitreous hemorrhage. DESIGN Observational case report. PARTICIPANT A 50-year-old woman with subarachnoid hemorrhage and unilateral vitreous hemorrhage. METHODS Detailed examination with fluorescein angiography and funduscopy. MAIN OUTCOME MEASURES Site of dye leakage on fluorescein angiography in the eye with vitreous hemorrhage. RESULTS Fluorescein angiography showed the leakage site at the margin of the disc in the eye with vitreous hemorrhage after the vitreous hemorrhage had been removed. CONCLUSIONS The damage to peripapillary tissues demonstrated by fluorescein leakage suggests that intracranial hypertension affects peripapillary structures through the intervaginal space of the optic nerve sheath.

Metastatic orbital tumors in Japan: A review of the literature

A review of reports on metastatic orbital tumors published from 1903 to 1998 in Japan revealed 128 patients, 74 males, 52 females and 2 whose sex was not recorded. The average age was 44.8 years, but varied depending on the primary tumor. Since 1980, metastatic orbital tumors have increased in Japan, especially those from the lung, liver and adrenal gland, while metastasis from the stomach has decreased slightly. Metastasis from the breast is still common. Most metastatic orbital tumors were from the lung, followed, in order, by breast, liver, adrenal gland and stomach. Males had four times as many metastatic orbital tumors from lung cancer than did females; only females had metastases from breast cancer; almost 90% of metastases from hepatoma were in males; metastasis from renal carcinoma was 2–3 times more common in males than in females. Metastasis from the liver and stomach is seen more frequently in Japan than in the United States and Europe. Ocular signs due to orbital metastases from hepatoma, neuroblastoma and gastric cancer were apt to appear earlier than the signs of the primary lesion. Metastases to the orbit were frequently bilateral in patients with neuroblastoma and malignant lymphoma. Specific ocular signs such as ecchymosis and conjunctival hemorrhages were seen in orbital metastasis from neuroblastoma and seminoma, while ocular pain was characteristic of malignant lymphoma. Orbital metastasis was very rare in patients with carcinoma of the uterus, ovaries, bladder, pancreas, colon or rectum in both Japan, the United States and Europe.

Anticoagulation Therapy and Ocular Surgery

BACKGROUND AND OBJECTIVE It is not rare for patients receiving anticoagulant therapy to undergo ocular surgery; however, there are no clear guidelines with reference to the operative management of the eye. This study examines the complications in patients receiving anticoagulant therapy who undergo ocular operations and suggests a management regimen for these patients. PATIENTS AND METHODS The authors retrospectively analyzed 52 patients receiving anticoagulant therapy who underwent ocular surgery between 1993 and 1995. Data included sex, age, reason for anticoagulant therapy, operative procedure, complication rate, and length of time anticoagulant therapy was stopped or reduced prior to surgery. To show the base-line complication rate at their institution, data of patients not receiving anticoagulation therapy were added. RESULTS Ticlopidine hydrochloride, an antiplatelet drug, was administered to 24 patients. Warfarin sodium was administered to 8 patients, heparin was administered to 8 patients, and other anticoagulants were administered to 20 patients. There were no significant differences in complications between the groups that stopped or reduced anticoagulant therapy and those that did not, but speech disturbance due to thrombotic complication occurred in 1 of 10 patients in whom ticlopidine hydrochloride was stopped or reduced. Hemorrhagic complications occurred in 50% of those who continued ticlopidine hydrochloride, but in none of those who discontinued it (P = .019). There was a significant difference in hemorrhagic complications after cataract surgery between the phacoemulsification, aspiration, and intraocular lens implantation (PEA + IOL) and the planned extracapsular cataract extraction and intraocular lens implantation (PECCE + IOL) groups that continued the drug (P = .0011). No patients showed visual acuity reduction due to hemorrhagic complications. CONCLUSIONS To avoid life-threatening systemic complications, one need not always stop anticoagulant therapy before performing only cataract surgery. Cataract surgery in patients receiving ticlopidine hydrochloride should be performed with PEA + IOL via a small sclerocorneal or a corneal incision. In cataract surgery for patients receiving anticoagulant therapy, hemorrhagic complications are more frequent than in patients not receiving anticoagulant therapy.

Microvascular architecture of the rat choroid: Corrosion cast study

This study presents the details of the microvasculature of the rat choroid visualized by scanning electron microscopy of vascular corrosion casts. Wistar Kyoto rats were anesthetized with intraperitoneal sodium pentobarbital. The vascular system was perfused with heparinized saline, and Mercox resin was injected into the cannulated carotid arteries. After polymerization of the resin, the vascular casts were macerated with potassium hydroxide, washed with water, and freeze dried. The casts were examined with a Hitachi S‐2360N scanning electron microscope (SEM). Corrosion casts of the entire choroidal vasculature revealed that the two long posterior ciliary arteries supplied the entire uveal vasculature. In the posterior choroid, these arteries formed five to seven branches on each side supplying the adjacent choriocapillaris. No interarterial or arteriovenous anastomoses were seen. The choriocapillaris appeared as a nonhomogeneous and nonlobular monolayer capillary network, consisting of dense honeycomb and irregular patterns. There are two distinct venous systems in the rat choroid. The venous blood from the central region, peripapillary choroid, and sometimes the optic nerve head drain into the posterior ciliary vein. The venous blood from the iris, ciliary body, anterior choroid, and half of the posterior choroid drain into the vortex veins. Corrosion casts and the SEM have shown details of the choroidal vascular architecture. These three‐dimensional observations indicate that the rat choroidal vasculature has different features from those of humans and other primates. Despite these interspecies differences, the establishment of a thorough baseline concept of choroidal vasculature should permit additional studies of the choroidal pathology and enable the proper interpretation of results from rat experimental models for extrapolation to humans. Anat Rec 264:63–71, 2001.

RETINAL CAPILLARY CHANGES IN OTSUKA LONG-EVANS TOKUSHIMA FATTY RATS (SPONTANEOUSLY DIABETIC STRAIN) : ELECTRON-MICROSCOPIC STUDY

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a spontaneously diabetic strain with polyuria, polydipsia and mild obesity. The pathological features of OLETF rats closely resemble those of patients with non-insulin-dependent diabetes mellitus. The purpose of this study is to investigate the retinal capillary changes in the OLETF rat and to confirm the valuability of the OLETF rat as the model of diabetic retinal disease. One-month-old male OLETF rats and age- and sex-matched Long-Evans Tokushima Otsuka (LETO) controls were supplied by Otsuka Pharmaceutical Co. Ltd. (Tokushima, Japan). Body weight and blood sugar levels were measured monthly. Their eyes were enucleated 14 months after birth. Ultrathin sections were made and examined with a transmission electron microscope. According to their location, two kinds of retinal capillaries were differentiated: those in the nerve fiber layer (NFL) and those in the outer plexiform layer (OPL). The image of each capillary was transferred to a computed image analyzer, and basement membrane thickness and the ratio of the pericyte area to total capillary cross-section area were determined. Corrosion casts of retinal vessels were made and examined with scanning electron microscopy (SEM). OLETF rats gained more weight than LETO rats from the beginning, and the difference increased gradually with age. The blood sugar level of OLETF rats was higher than that of LETO rats after 5 months of age. In the retinal capillaries of 14-month-old OLETF rats, basement membranes were significantly thicker (OLETF: 209 ± 51 nm in NFL, 132 ± 23 nm in OPL; LETO: 118 ± 28 nm in NFL, 79 ± 14 nm in OPL), and the ratio of pericyte area to the capillary cross-section area was significantly lower than that of the controls (OLETF: 0.131 ± 0.92 in NFL, 0.111 ± 0.102 in OPL; LETO: 0.288 ± 0.142 in NFL, 0.198 ± 0.136 in OPL). The endothelial cell cytoplasm had degenerated. SEM examination of the vascular corrosion cast of a 14-month-old OLETF rat showed caliber irregularity, narrowing, tortuosity and loop formations of capillaries. The morphological changes in the retinal capillaries of OLETF rats were similar to those seen in diabetic patients. The OLETF rat may be a useful animal model for the study of ocular diabetic complications in humans.

Vascular Changes in Retinas of Spontaneously Hypertensive Rats Demonstrated by Corrosion Casts

The changes in the capillary network of the retina in spontaneously hypertensive rats (SHR) were demonstrated by scanning and transmission electron microscopy. Corrosion casts with scanning electron microscopy provided a three-dimensional view of the microvasculature of the rat retina and could detect the conspicuous features of the retinal vasculature in SHR. In general, when hypertension lasted for 6-7 months in SHR, tortuosity of the retinal vessels was noted, and later the SHR retina showed increased tortuosity and generalized narrowing of the vessels, localized constriction of the veins, arteriovenous crossing defects, and marked capillary changes, such as caliber irregularity, narrowing, bead-like capillaries, loop formation and localized obliteration. At a later stage, when the blood pressure had been sustained for a long time, there was marked capillary constriction which first affected the superficial capillary network, then scattered capillary network constriction and finally capillary dropout. Transmission electron microscopy revealed narrow capillary lumina and thin endothelium with scarce cytoplasmic components and damaged pericytes. These morphological changes in the capillary network were probably due to structural damage to the endothelial cells, facilitated possibly by compression of the precapillary arterioles. The severity of these changes was usually proportional to the degree and duration of hypertension. These findings indicate that the retinal capillary changes are probably related to hypertension.

Development of the eyeball during fetal life.

Two hundred fifty-two undamaged human fetuses without external malformations were supplied by the human embryo and fetus collection of the Department of Anatomy, Kyoto University. The sagittal, vertical and horizontal diameters of the eyeball were measured by micrometer, and the transverse, vertical and horizontal circumferences of the eyeball were measured by mapmeter from photographs of the side views of the eye. All the diameters of the eyeball showed a parallel linear increase from the 12th to the 40th week of menstrual age. The increase of circumferences of the eyeball paralleled each other throughout the 12th to the 40th week. It is significant that the sagittal diameter of the eyeball is shorter than the vertical and transverse diameters during fetal life. The vertical meridian circumference of the eyeball is also shorter than the transverse and horizontal meridian circumferences during fetal life. These findings suggest that many infants are apt to have hyperopia at birth.

Quantitative receptor autoradiographic analysis for angiotensin II receptors in bovine retinal microvessels: quantitation with radioluminography.

Summary1.Specific125I-Sar1, Ile8-Angiotensin II (125I-Sar1, Ile8-AII) binding sites in bovine retinal microvessels were investigated using the quantitative receptor autoradiographic method with pellet sections.2.A quantitation was made with the computerized radioluminographic imaging plate system, a newly developed and highly sensitive method. Binding characteristics of the retinal microvessels were compared with those of the cerebral microvessels and the retinal macrovessels.3.We isolated microvessels from the bovine retina and bovine cerebral cortex using the method composed of two-size sievings and high-speed homogenization with a Polytron. The isolated microvessels were composed of capillaries, and the retinal macrovessels contained vessels with smooth muscle.4.There were specific binding sites for125I-Sar1, Ile8-AII which were single and of a high affinity, in both the cerebral and the retinal microvessels and the retinal macrovessels. There were no differences in affinity between the vessels, but the retinal microvessels did have a higher density of binding sites than the cerebral microvessels.5.The method we used is simple and sensitive for detecting and characterizing125I-Sar1, Ile8-AII binding sites in retinal capillaries. Knowledge of the existence of large numbers of specific binding sites, candidates of physiologically active angiotensin II receptors, aids with understanding the regulatory roles of angiotensin II in the blood-retinal barrier.