Shigekazu Uga

Retinal degeneration in rats exposed to an organophosphate pesticide (fenthion)

Pigmented (Long-Evans) and albino (Wistar) rats were chronically exposed to an organophosphate pesticide (fenthion). Fenthion (50 mg/kg) was administered subcutaneously twice a week for 1 year; the total dosage for each animal ranged from 1.6 to 1.8 g. Concurrent with the fenthion administration, the amplitude of the scotopic electroetinogram (ERG) gradually declined, disappearing by the 12th month in all treated pigmented rats. For the albino experimental rats, however, the ERG amplitude disappeared as early as the 6th month in 7 out of 15 treated animals. Funduscopically, degeneration of the retina was observed in all rats when ERG responses had disappeared. Histopathological studies confirmed degeneration of the sensory retina and marked abnormalities in the pigment epithelium cells. Treated pigmented rats also had reduced a rhodopsin concentration in the retina by the 3rd month even though the photoreceptors were structurally normal. Interestingly, the plasma vitamin A levels remained normal and liver stores of vitamin A actually increased during the course of the study. Levels of butylcholinesterase in plasma and liver, on the other hand, were extremely reduced after 3 months of fenthion treatment. In general, the biochemical and functional (ERG) changes appeared before any structural damage could be detected in the retina.

Electron-Microscopic Study of Iris Nerves and Muscles in Diabetes

The ultrastructure of the iris muscles and innervating nerves in patients with diabetes mellitus and approximately age-matched controls was examined by electron-microscopy. The specimens were obtained during cataract surgery. There were definite histopathological alterations at the nerve terminal innervating the dilator muscle, e.g. the presence of mitochondrial abnormalities, dense bodies and lamellar structures. No change was noted at the nerve terminal to the sphincter muscle. Moderate involvement of the muscle, especially at the sphincter, was observed in the specimens of diabetics. The control specimens had no change at the nerve terminals, while moderate change was observed at the sphincter muscle. Therefore, the change in the sphincter seen in the specimens of diabetics seemed to be mainly the result of the aging process, though the existence of early sympathetic neuropathy was confirmed.

Ultrastructure of Iris Muscles in Diabetes mellitus

Fine structure of iris muscles from 16 iris specimens in patients with diabetes mellitus were investigated by electron microscopy, and the results were compared with those of 10 specimens of senile cataract eye without diabetes of the corresponding age groups. Significant ultrastructural changes were extensively found at the regions of the dilator, sphincter muscles and of the nerves endings adjacent to them. To cytoplasm of the muscle cells was partly occupied by membraneous structures with concentric lamellar appearance. Cytoplasmic vacuolations were noted in the muscle cells. An increased number of the lipid droplets associated with pigment granules in the cells was found in all diabetic iris specimens. These three kinds of pathological changes (lamellar structure, vacuole, and lipid droplet) increased depending on the duration as well as the control of the disease. Althought these findings were noted both in the sphincter and dilator muscles, the latter seemed to be more severely affected. Degenerative nerve endings containing lamellar membraneous structures were observed in a few moderate cases. Nerve fibers frequently diminished in diabetic patients, especially in severe cases with longer duration together with poorly controlled cases. These findings suggest that diabetes involves the iris muscle cells as well as the nerves, and these changes might be a reason to produce a pupillary abnormality.

Morphological study of a hereditary rat cataract

Lenses of ICR/f stain rats with hereditary cataract were examined by light and electron microscopy. The earliest change was the frequent occurrence of displaced or migrated nuclei in the posterior sutural area at birth. Unusual dense fibers at the bow area, and swollen fibers in the posterior cortex were observable by just 2 weeks of age. At 4 weeks of age, the appearance of the dense fibers at the bow area became more frequent, and the lenticular nucleus was formed at the center of the lens. At this time the cellular extensions of the posterior cortical fibers began to be interrupted around the posterior sutural area, which might represent a critical change. Following this change, small amounts of liquid were accumulated at the posterior subcapsular region just behind the bow area by 6 weeks of age. The lenticular nucleus was gradually shifted to a posterior location. Between 10 and 11 weeks of age, increased areas of liquefaction extended into almost all the area of the posterior subcapsular region, and as the posterior suture line separated, the opacification rapidly appeared. This animal model seems to suggest the importance of successive formation in the posterior suture.

Morphological study on cataractogenesis of the Nakano mouse lens

Abstract · Background: Although some histopathological features on the Nakano mouse lens have been pointed out by a few investigators, there seem to have been no detailed studies on the sequential changes that occur. · Methods: We used the following two approaches: (1) Observation of the whole lens by dissection microscopy and (2) light and electron microscopic examination of the sectioned lens specimen. · Results: (1) The Nakano mouse lens showed sustained transparency up to 19 days after birth, fine opacity at the 20th day, and development of a mature cataract around the 30th day. In addition, although the Y-shaped posterior suture was normal at the 15th day, bending of the suture line appeared around the 19th day. (2) The cataractous lens revealed degeneration of the epithelial cells and adjacent anterior cortical fibers at the 10th day. Swelling of the anterior cortical fibers became prominent, and swelling of the posterior cortical fibers occurred by the 15th day. Upon separation of the suture around the 20th day, fine opacity occurred in the perinuclear zone, which extended to the anterior cortex and finally led to the formation of a mature cataract. · Conclusions: These results indicate that epithelial degeneration is a major feature of cataract in the Nakano mouse, and the subsequent lens fiber swelling and posterior sutural separation are the underlying causes of the development of opacity.

Histopathological Study of Anterior Segments of the Eye with the Intraocular Lens in the Posterior Chamber

We conducted a histopathological study of the anterior segments of the eye of a female who died 2 years after insertion of an intraocular lens (IOL), which had one end of the supporting loop inserted in the lens capsule bag and the other in the ciliary sulcus. No changes were noted in the iris and ciliary body located within the capsule. However, in the part in the ciliary sulcus, the iris root was bent towards the chamber angle and the trabecular meshwork was depressed. Moreover, the ciliary body exhibited hyaloid degeneration. A secondary cataract had formed in the periphery of the IOL. These findings suggest that the ideal site of IOL insertion might be within the capsule.

Morphological Analysis of Iodoacetic Acid-Induced Cataract in the Rat

Purpose: To clarify the mechanism underlying the development of cataract in the rat lens after intraperitoneal administration of iodoacetic acid (IAA). Methods: (1) The 2% IAA dissolved in saline solution was injected at a dose of 40 mg/kg body weight into the rat peritoneal cavity. The retina and lens were intermittently extirpated and were examined by light and electron microscopy. (2) Two kinds of tracer, Evans blue (EB) and horseradish peroxidase (HRP), were injected into the tail veins and anterior chamber, and were observed with dissecting and electron microscopes. Results: (1) Four weeks after administration, a part of the lens epithelium at the lateral side of the lens was degenerated, and the lens nucleus developed faint turbidity after 8 weeks. After 16 weeks, the nuclear turbidity could not be observed because mild cortical opacity was developing. The epithelial degeneration recovered from around 12 weeks, and instead of spherical nuclei, elliptical nuclei appeared. (2) The EB dye injected into the tail vein significantly stained the ciliary body, where the anterior and posterior ciliary arteries anastomosed. EB injected from the lateral side of the lens was seen to move towards the lens nucleus. Electron microscopically, the epithelial degeneration of the ciliary body was observed. The incorporated HRP substance was found in the cytoplasm of the nonpigmented cells of the ciliary epithelium at an early stage after IAA administration. Conclusion: IAA injected intravenously first developed epithelial degeneration at the lateral side of the lens. This change induced swelling of the lens fibers in the lens nucleus. Recovered epithelial cells had a transformed nucleus, and in turn the cortical cataract was induced by a differentiation disorder of the lens fibers. These results indicate that the breakdown of the blood-aqueous barrier in the nonpigmented epithelium of the ciliary body is a trigger to cause the cataract. The IAA-induced cataract may be useful as an animal model of human age-related cataract.

Morphological study of the cataractous lens of the senescence accelerated mouse

A murine model of accelerated aging, the senescence accelerated mouse (SAM), has been developed. There are three accelerated senescence-resistant (SAM-R) strains and eight senescence-prone (SAM-P) strains. The SAM-P strains have an earlier onset and more rapid advancement of senescence resulting from a significantly shorter lifespan compared with the SAM-R strains. Spontaneous cataracts have been found in some individuals of the SAM-P/9 strain. The SAM -P/1 strain, which was used in the present study, has such systemic senescent characteristics as senile amyloidosis and alopecia, but it was previously thought that cataract does not occur in this strain. However, we found cataractous changes in the lens of these animals at early stages of their life. The earliest change was the appearance of a ripple-mark body at about 3 months of age. The number of rippled rings increased with age. These changes later induced refractive distortion of retinal vessels. Whole-mount flat preparations of the epithelium showed that the number of cells was markedly decreased at the advanced stages of cataract. At the late stages of life the lens cortex became liquefied and developed into a mature cataract. Cataract formation in this strain may be related to reduced viability of the lens epithelium.

Histopathological study of Emory mouse cataract

Lenses of Emory mice, ranging in age from 7 days to 15 months, were studied by light and electron microscopy. The earliest change was acellularity in the lens epithelium, which was found at postnatal day 14. This acellularity was relatively mild but constantly occurred throughout the experimental course. The early cortical fiber change was swelling in the anterior region of the lens at 1 month of age. At 2 months of age some cell extensions towards the capsule appeared at the basal surface of the posterior cortical fibers near the equatorial region, and their height and number had greatly increased by 4 months of age. Following this change, there was an enlargement of nuclei in the bow area, swelling of cortical fibers, and separation of the posterior suture line. These changes became severe by 6 months of age. When the separation of the posterior suture and disturbance of the posterior cortical fibers became markedly severe, the cataract reached a mature stage, showing the complete opacity of the cortex. This animal model appears to indicate that the viability and/or behavior of the epithelial cells is important for maintaining the transparency of the lens throughout the lifespan.

Ultrastructural Study of Rainbow Trout Lenses Incubated under Various Conditions

The pathology of rainbow trout lenses incubated in various media and at various temperatures was examined by electron microscopy. After incubation at 0 degrees C for 5 h, no changes were observed in transparency and cytology. Irreversible warm cataract occurred at 37 degrees C, which corresponds to the body temperature of mammals. The degree of turbidity increased depending on incubation time. The ultrastructure of warm cataract in short-term incubation was characterized by the appearance of dense substances in the epithelium and swelling of the lens fibers. When the incubation time was prolonged up to 3 h, the turbidity increased and cellular disorders became severe. The volume of the dense substances increased also. A slight but detectable haziness of the lens was observed after incubation with calcium-free medium. Pathological findings in this case consisted of disorders of the intracellular membrane system in the epithelium and swelling of the lens fibers. These results suggest that the rainbow trout lens has a lower optimum temperature compared to the mammalian lens but requires the same Ca2+ concentration.