Toichiro Kuwabara

The maturation of the lens cell: a morphologic study

Abstract Cytologic details of the lens cells of the human and monkey have been studied with specific emphasis on their maturation process. Lens cells maintain the basal attachment until the nuclei are eliminated. After the denucleation, the cells develop specific joining apparatus. The mature lens cells, which occupy the major part of the lens, are held to each other firmly by knob and socket joints in the superficial cortex and by fine ridges in the deep lens. Cells in all maturation stages are present within the lens. Except for the decreased number of the elongating cells at the bow zone in older age, there is no specific structural difference between lenses of different age groups.

Localization of Aldose Reductase in the Human Eye

The presence of the enzyme aldose reductase is increasingly being linked to diabetic complications. The distribution of this enzyme in human cornea, lens, retina, and optic nerve has been studied using specific antibodies against purified human placental aldose reductase raised in both rabbit and goat. The antisera from both animals gave equal, specific reactions. In frozen sections of ocular tissues, significant aldose reductase localization was reproducibly demonstrated in the endothelium and epithelium of the cornea and in the basal cell layers of the conjunctiva. In the lens, staining was observed in the epithelium and superficial lens fibers. In retinal sections, the presence of aldose reductase was demonstrated in the Muellers cells, especially near the inner limiting membrane. It was also found in some ganglion and cone cells. In the optic nerve, positive staining was observed in the axon. All other cells of the tissues examined revealed Only weak, nonspecific Staining.

REMOVAL OF CORNEAL CRYSTALS BY TOPICAL CYSTEAMINE IN NEPHROPATHIC CYSTINOSIS

In patients with nephropathic cystinosis, corneal crystals develop by one year of age; they progressively accumulate and eventually cause recurrent corneal erosions and photophobia. After an in vitro study of cystinotic corneal stromal cells showed cystine depletion by cysteamine and after topical cysteamine was determined to be nontoxic in rabbits, we performed a controlled double-blind clinical trial of 10 mM cysteamine eyedrops in young patients with cystinosis, using one eye for treatment and the other as the control. Two children begun on the protocol before two years of age had a striking decrease in the number of corneal crystals in the cysteamine-treated eye within four to five months of entering the study. Cysteamine eyedrops appear to be safe and efficacious in the short-term treatment of patients with cystinosis who are under two years of age. The long-term value of such treatment and its effectiveness in older patients remain to be determined.

Histologic changes in the inner retina of albino rats following intravitreal injection of monosodiuml-glutamate

Monosodiuml-glutamate is known to cause intracellular swelling, necrosis, and disappearance of most inner retinal neurons, with concomitant thinning of inner retinal layers within hours after subcutaneous injection into neonatal rodents. A similar process can be observed in adult rat retina after intravitreal glutamate injection. To better describe and compare this process with that reported after systemic application, adult Spraque-Dawley rat eyes were intravitreally injected with 1 μmol monosodiuml-glutamate and the retinas studied by LM and EM over a 2-month period. Results demonstrated that adult rat retina 6experienced severe degenerative changes which progressed in two stages: an initial stage of massive intracellular swelling and a second stage of necrosis and cell loss. Degeneration involved ganglion and inner nuclear layer cells. Inner retinal thickness decreased concurrently. By 2 months postinjection, degenerative changes in rod spherules and some loss of photoreceptor nuclei were observed. Both time course and severity of the lesion differed from that described in prior studies after systemic treatment.

Myopathy and Cystine Storage in Muscles in a Patient with Nephropathic Cystinosis

NEPHROPATHIC cystinosis is a lysosomal storage disorder characterized by the appearance of renal tubular Fanconis syndrome in the first year of life and by growth retardation, progressive photopho...

Immunohistologic findings and results of treatment with cyclosporine in ligneous conjunctivitis

Using immunohistochemical techniques, we studied ligneous conjunctival lesions from two patients. A significant immune reaction was detected that was characterized by activated T lymphocytes and focal accumulation of plasma cells and B lymphocytes. Immunofluorescent studies demonstrated that IgG was a prominent component of the amorphous hyaline material seen in these lesions. After previous treatment methods had failed, both patients were treated with excisional biopsy and topical cyclosporine. Patient 1 had a dramatic response, with complete resolution of the lesions. Patient 2 had a significant improvement resulting in small, slow-growing recurrences instead of the rapid and extensive recurrences that occurred before treatment with cyclosporine.

The roles of vitamin E and unsaturated fatty acids in the visual process.

Relatively high proportions of long-chain, polyunsaturated fatty acids seem to be required in rod photoreceptor membranes in order to provide the precise microenvironment for the proper function of the visual pigment rhodopsin. At the same time, such high levels of lipid unsaturation put the photoreceptor membranes at a high risk for autoxidation. The antioxidant vitamin E which can minimize autoxidation of polyunsaturated fatty acids is found in rather high concentrations in the outer segment membranes. Dietary deficiency in vitamin E induces disintegration of rod outer segment membranes, probably by increasing autoxidation. Also, it greatly accelerates the accumulation of aging pigments in the retinal pigment epithelium, probably because these lipofuscin granules do indeed represent the end products of lipid peroxidation. Vitamin E supplements, up to threefold normal levels, appear to provide no significant protection of the retina from light damage produced either by short but acute or by long-term, low level exposures to light. This is not consistent with current theories which implicate lipid peroxidation in the destruction of rod outer segments in light damaged retinas; more work is needed before any relation between retinal light damage and vitamin E levels can be assessed. Surprisingly, the amount of lipofuscin granule accumulation in the retinal pigment epithelium is influenced dramatically by dietary levels of vitamin A. Even retinas lacking a source of polyunsaturated fatty acids from rod outer segments still may accumulate massive lipofuscin if dietary vitamin A is provided. Perhaps vitamin A, which has such a dynamic relationship with the retinal pigment epithelium, becomes oxidized, and then contributes to the formation of a lipofuscin-like pigment. Centrophenoxine, a drug claimed to be effective in reversing the accumulation of age-related lipofuscin in the central nervous system, has no obvious effect in the eye or uterus in removing the lipofuscin granules induced by vitamin E deficiency. Microperoxisomes are abundant in the retinal pigment epithelium, and may be associated with rapid lipid turnover and/or utilization of lipid soluble vitamins. Their potential roles, however, need further documentation and clarification. Recently developed techniques and new discoveries in lipid research open the way for many fruitful studies on the interactions and precise roles of lipids and lipid-soluble vitamins in vision.

Optic Neuropathy Presumably Caused by Vincristine Therapy

A 36-year-old man with Hodgkins disease developed symmetric optic neuropathy after treatment with nitrogen mustard, vincristine, procarbazine, and prednisone. Histopathologic sections of the eyes showed loss of ganglion cells in the macular region and atrophy of the corresponding fibers in the optic nerve. Vincristine is presumed to have been the cause of the optic neuropathy because of its recognized neurotoxicity and its temporal relation to the onset of the visual complaint.

Swelling of the lens fibers.

Abstract Lens cells of congenital mouse cataract (Nakano and Fraser strains) and galactose-fed rats were studied by scanning electron microscopy. Similarly lens cells of normal young mice and rats were examined as controls. Normal lenses of young rodents consist of lens fibers in all maturation stages which have been demonstrated in humans and in monkeys. Lens cells in the congenitally cataractous lenses are irregular in size and shape in the earlier stage of the cataract formation. Swelling of the lens cell occurs corresponding to the occurrence of early optical opacity. Swelling of the cell occurs segmentally in congential cataractous lenses; in the apical ends (Fraser) and in the posterior ends (Nakano). Similar swelling of the lens cell is observed in the main cell body in the superficial lens cortex of galactose-fed rats. However, numerous intercellular cysts are formed by the accumulation of fluid which may have been pumped out of the cells before the cells became degenerative. These numerous shrunken fibers are present among swollen cells in both congenital and galactose-induced cataractous lenses.

TETRAZOLIUM STUDIES OF THE RETINA: III. ACTIVITY OF METABOLIC INTERMEDIATES AND MISCELLANEOUS SUBSTRATES

‘I’svo constrastinug l)att(’rmsS of t(’trazoliuns preoipitatioui by thse rrtimua svere described in previous papers of thus so’ries (1 , 2) . One patterms resulted from the Use of hactate-DPNt as a sui)strate an(I the othser fromus thur use of succimsate. Thur former imuduceot aetiyity predonsimsantly in thur glial and ganglion cells svhereas the latter induced activity in thur phsotoreceptors, the reticular layers, auud the nerve fiber layer. With these two patterns servimsg as a basis for com-