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The effect of glutathione (GSH) isopropyl ester on the progression of X-ray-induced cataract was investigated in rats. Intraperitoneal administration of 20 mg/kg GSH isopropyl ester, three times weekly, 1 day after a single irradiation dose delayed the progression of X-ray-induced cataracts significantly. The amount of non-protein SH groups and the Na+/K+ ratio in the lenses of drug-treated rats were maintained at the normal levels even 27 weeks after irradiation. Posttreatment with the drug resulted in a significantly lower level of malondialdehyde in the irradiated lenses than in the nontreated lenses. When 500 mg/kg GSH-isopropyl ester was administered by i.p. injection to normal rats, the GSH-ester was detected in plasma and aqueous humor after 15 min. In the lenses of the GSH-isopropyl ester-injected rats, the GSH level was 120% of that in the non-treated rats after 4 h, suggesting that GSH-isopropyl ester is transported from the aqueous humor to the lens and there converted to GSH after about 4 h. Our observations lead us to conclude that the delay of X-ray-induced lens opacity progression is due to maintenance of normal lenticular GSH levels achieved by post-irradiation administration of GSH-isopropyl ester. However, continuous administration of 100 mg/kg after irradiation had no effect on the progression of cataracts induced by X-rays.

The effect of 2-mercaptopropionylglycine on the development of cataract induced by a single dose of X-ray (10 Gy) was investigated in rats. Intraperitoneal injection of 20 mg/kg, three times weekly starting 1 day after irradiation delayed the development of X-ray-induced cataracts significantly. The amounts of non-protein SH groups, malondialdehyde and the Na+/K+ ratio, in the lenses of rats post-treated with the drug were significantly maintained at normal levels even at 27 weeks after irradiation. On the other hand, a single administration of 250 mg/kg of the compound, 30 min prior to irradiation had no effect on cataract progression induced by X-ray.

Sulphur-containing compounds in the lens were studied in relation to galactose cataract formation. Female Wistar rats were fed a 35% galactose diet and the changes in lens sulphur concentration and its distribution on a gel filtration column were compared with age-related changes. Concentration of sulphur in the whole lens decreased with time. A low constant level was attained on the fifth day of the galactose diet. A decrease of sulphur concentration in the soluble fraction of the lens paralleled that of the whole lens which was correlated with the decrease of glutathione and taurine concentrations on a gel filtration column by high-performance liquid chromatography-inductively coupled argon plasma atomic emission spectrometry (HPLC-ICP). Concentration of magnesium in the lens decreased after the fifth day, while the ratio of sodium to potassium increased. These changes in sulphur-containing compounds and metals were observed prior to the onset of cataract formation.

The ultrastructure of gap junctions throughout the human foetal lens was observed. By freeze-fracture analysis, we observed numerous gap junctions in both lens cortex and lens nucleus. Comparison between lens cortex and lens nucleus showed that the gap junctions of lens nucleus are characterized by extreme mosaics of closely apposed P- and E-faces in junctional areas, though no significant difference in the area of gap junctions was observed between lens cortex and lens nucleus. In addition, some morphological variations, such as the smooth domains without particles or pits in junctional areas and the reticulated figures of gap junctions, were observed only in the lens nucleus. We also observed by thin-section electron microscopy that cell membranes of human foetal lens nucleus, as observed in the lens cortex, are mainly composed of continuous lipid bilayer and junctional structures. We concluded that characteristic morphology of lens gap junctions, as observed in the cortex of human foetal lens, is mostly preserved in the human foetal lens nucleus, although some depth-dependent alterations were also observed.

Previous investigations demonstrated that fibronectin is an essential adhesive glycoprotein for the corneal epithelial cells. Fibronectin mediates attachment and spreading of the corneal epithelial cells. However, it seems to be important to know the changes in cellular receptor activity in order to understand the interactions of corneal epithelial cells and underlying extracellular matrix. In this investigation, we studied the effects of various culture times and conditions on the receptor activity of rabbit corneal epithelial cells for fibronectin. The cultured cells were placed on tissue culture plates that were coated with various concentrations of four extracellular matrices: fibronectin, laminin and collagen types I and IV. Freshly isolated corneal epithelial cells without culture did not spread on fibronectin and laminin; they spread only on collagen types I and IV. When the epithelial cells were cultured for 12 h or more, they spread on fibronectin. However, the spreading of the cells on collagen types I and IV was the same regardless of the culture period (up to 20 h). Only a small number of epithelial cells spread on laminin at the highest concentration examined after culture for 12 h or more. Thus, the corneal epithelial cells responded differently to fibronectin, collagen types I and IV, and laminin. Perhaps the receptor for fibronectin appears when epithelial cells are cultured, but the receptor(s) for collagen types I and IV are always present on the cell surface of corneal epithelial cells.

Recently, alterations in contrast (modulation) sensitivity functions of patients with high refractive errors have been noted. For example, this seems to be a common finding in aphakia. In some measure the observed alterations are due to the effect of the corrective lens and the optics of the eyes. These optical effects (in addition to blur) must be factored out in order to determine whether residual effects on the visual system remain. The argument is applicable to photographs of sine wave fringes as well as devices designed to produce interference patterns directly on the retina. A simple means for largely correcting these lens effects is discussed.

A collagenase that can digest both collagen fibers in the stroma and the native collagen molecule was found in rabbit corneal epithelium, using a tissue culture assay. Calf, chicken and fetal calf serum added to the tissue culture media inhibited the collagenase, while human and rabbit serum were not inhibitory. Edathamil calcium disodium demonstrated a potent inhibitory effect on the enzyme with minimal toxicity to the epithelial cells. The clinical implications of a corneal collagenase are discussed.

The dynamic visco-elastic properties of human, monkey and rabbit lenses have been measured with a dynamic rheometer. The value for the apparent elastic modulus (Young modulus) of the lens was found to be 10 5 –10 6 dyne/cm 2 in humans and 10 4 –10 5 dyne/cm 2 in monkeys and rabbits. The value for the loss tangent was 0·3–0·4 in the human lens and 0·3–0·6 in rabbit and monkey lenses. Elastic moduli and loss tangents of the lenses showed poor dependence on temperature at 15°–55°C and on frequency of oscillation at 0·01–25 c/s. The lenses showed linear viscoelasticity when the amplitude of oscillation was below 0·02 mm, and they showed non-linear visco-elasticity when the amplitude exceeded 0·03 mm.

Under the conditions of this study, systemically or topically applied thimerosal was found to have no teratogenic effect even when given in concentrations approaching the 50% lethal dose of these compounds. A comparison of topical and subcutaneous administration of thimerosal to rabbits shows that a substantial concentration of mercury was present in blood and tissues of the treated animals and their offspring. Thimerosal was found to cross the blood-brain and placenta barriers.

Nonradioactive idoxuridine (IDU,5-iodo-2'-deoxyuridine), while not teratogenic to rats, does produce fetal maliformations in rabbits when administered topically to the eye in doses similar to those used clinically, 0.1% four times a day for 12 days. These maliformations include exophthalmos and clubbing of the forelegs. By contrast, trifluorothymidine (F3TdR), another highly effective antiherpetic agent currently under investigation but not available for general use, was found not to be teratogenic to rabbits, even when given in concentrations tenfold greater than the doses used to produce idoxuridine teratogenicity.

Collagenolytic activity was found in bovine corneal epithelium using a synthetic substrate. Increased levels were found after physical disruption of the epithelial cells. This activity was inhibited by disodium ethylene diamine tetraacetate. The release of a collagenolytic enzyme from traumatized epithelial cells may be of clinical importance in the pathogenesis of corneal stromal ulcerations.

Peptidase activity, operative at neutral pH, was found in bovine cornea and conjunctiva with a synthetic substrate assay. The same peptidase was found previously in commercial bacterial collagenase preparations. Cell fractionation of homogenates revealed the activity to be maximal in the high-speed supernatant of the corneal and conjunctival epithelium, and in the intermediate fraction of the endothelium. There was no peptidase found in the stroma. EDTA, cysteine, calf serum and calf aqueous inhibited this activity. The specificity and advantages of the substrate are discussed, and the clinical implications of a collagenase-like peptidase system within the cornea are noted.

• Examination of 1,625 Japanese patients with keratoconus and 20 patients with pellucid marginal corneal degeneration showed that 17 patients with pellucid degeneration also had keratoconus in the central portion of the cornea. Three patients with pellucid degeneration without keratoconus showed bilateral involvement. Among the 17 cases of pellucid degeneration with keratoconus, eight patients showed bilateral involvement and the others showed unilateral involvement. Pellucid marginal corneal degeneration with or without keratoconus may be a variant of keratoconus or a different manifestation of the same etiologic factor.