Ceramides of human normal and cataractous lens.

Ceramides were quantitatively isolated from human normal and cataractous lens by solvent extraction, silicic acid chromatography, thin-layer chromatography, and gas-liquid chromatography. Only two species of ceramides with normal fatty acids were detected. In the mature cataracts, there was an increase in palmitate and nervonate at the expense of the other fatty acids. Due to the increase of 24 : 1, the ratio of 24 : 1/24 : 0 increased significantly from normals to cataracts. Sphinganine was the major long-chain base, but 4-sphingenine was also present. The total amount of ceramides in the immature and mature cataracts was 1.8 and 3.0 times higher than the normals of the same age group. Such an increase does not seem to be the result of an age-dependent process.

A new family of fucose-containing gangliosides isolated from human senile cataracts.

Gangliosides were isolated from human cataracts by solvent extraction, silicic acid chromatography, thin-layer chromatography and gas-liquid chromatography. A total of 11 resorcinol-positive bands were revealed by thin-layer chromatography. Bands 1, 5 and 7 were partially identified as hematoside. GM1 ganglioside and disialoganglioside by gas-liquid chromatography as the O-trimethylsilylated methylglycosides. In addition to galactose and glucose, fucose was found to be present in seven ganglioside fractions (bands 3, 4, 6 and 8-11). All these fucolipids contained N-acetylglucosamine in addition to sialic acid. Fucogangliosides G-3, G-4 and G-6 contained a 2:1 molar ratio of galactose to glucose, while G-8 had a galactose/glucose molar ratio of 1:1. Long-chain fatty acids constituted 60-77% of the total normal fatty acids in N-acetylgalactosamine-containing gangliosides, whereas the fucogangliosides contained primarily palmitate, although significant amounts of long-chain acids were also detected. The major long-chain base of the fucoganglioside was sphinganine (dihydrosphinogosine). The role of fucose-containing gangliosides in maintaining adhesions between lens membranes in cataracts is discussed with reference to glycosphingolipids in other tissues.

Distribution of salicylate in lens and intraocular fluids and its effect on cataract formation.

Retrospective studies on cataract development in patients with rheumatoid arthritis or osteoarthritis revealed a retardant effect of aspirin on diabetic and non-diabetic cataracts. The effect of aspirin is dose-dependent. The correlation coefficient between years delay for various cataracts subcategories versus aspirin taken (in tablets per day X years of intake) was 0.69. The ocular pharmacokinetics of 14C acetylsalicylic acid or salicylate were determined after intravenous or intraperitoneal administration to rabbits. 14C acetylsalicylic acid penetrates rapidly into rabbit lens and aqueous humor after intravenous administration. After intraperitoneal administration, salicylate levels in rabbit plasma, similar to those of humans receiving four to six aspirin tablets (325 mg each), result in accumulation of salicylate by lens (mean +/- SD) of 405 +/- 72 mumoles/g and 620 +/- 30 mumoles/g at two and four hours, respectively. At those dosages, salicylate is cleared in 24 hours from rabbit plasma and intraocular fluids, but retained by lens. Penetration of salicylate into rabbit lens and rat lens is dose-dependent. The retardant aspirin effect in diabetic cataracts is linked to inhibition of tissue aldose reductase and lens protein glycosylation. Deceleration of galactose cataract formation in rats occurs after daily salicylate intraperitoneal injections of 100 mg/kg a day.

Biosynthesis of neopterin, sepiapterin, and biopterin in rat and human ocular tissues.

Neopterin, sepiapterin, and biopterin synthesis by lens, retina, and ciliary body-iris of rat and human indicates pteridine formation from their precursor, GTP. The pteridine biosynthesis was higher in the retina (neopterin 422 +/- 27, 260 +/- 24; sepiapterin 135 +/- 12, 118 +/- 14; biopterin 76 +/- 10, 68 +/- 8 nanomoles/g soluble protein/hr, in rat and human, respectively) than in the ciliary body-iris and lens. The light-sensitive pteridines may protect eye tissues against the effects of sunlight in addition to their role in the hydroxylation of aromatic amino acids.

Free epsilon amino groups and 5-hydroxymethylfurfural contents in clear and cataractous human lenses.

The free epsilon-amino groups and 5-hydroxymethylfurfural (5-HMF) contents were determined in soluble and insoluble proteins of clear human lenses and diabetic and nondiabetic senile cataractous lenses. The free epsilon-amino group content of soluble proteins in diabetic cataracts was decreased by 37% (P less than 0.01), whereas in nondiabetic senile cataracts it did not differ from that of clear lenses. The free epsilon-amino group content of insoluble proteins both in diabetic and nondiabetic cataracts was decreased significantly (P less than 0.001, P less than 0.015, respectively). The 5-HMF content of soluble proteins in diabetic cataracts was increased by 52% (P less than 0.001), whereas in nondiabetic cataracts it did not change from that of clear lenses. The 5-HMF content of insoluble proteins in diabetic as well as in nondiabetic cataracts was increased significantly as compared to that of clear lens (P less than 0.001, P less than 0.001, respectively). The soluble protein of diabetic and nondiabetic cataracts was decreased with an increase in the insoluble protein content. These results suggest that nonenzymatic glycosylation plays a role in the conformational change of lens proteins in both diabetic and nondiabetic cataracts.

Diabetic complications in lens and nerve and their prevention by sulindac or sorbinil: two novel aldose reductase inhibitors.

Sorbitol, resulting from glucose metabolism through aldose reductase, may play a role in diabetic complications such as cataracts, neuropathy, and vasculopathy. Sulindac (Clinoril) and sorbinil, two inhibitors of aldose reductase, decreased sorbitol formation in cataract or nerve tissue incubated in high glucose TC-199 media. Sulindac, a widely used anti-rheumatic drug, may have clinical applications in preventing diabetic complications.

Café-au-lait spots of the fundus in neurofibromatosis.

Mild pigmentary changes found in the fundi of two patients with neurofibromatosis, resembled café-au-lait spots homologous with skin manifestations of the disease. In one, associated retinal hamartomas were present. The café-au-lait lesions were clinically distinct from previously reported uveal melanomas and may represent a hitherto unrecognized sign of ocular neurofibromatosis.

Marfan-like syndrome with lens involvement. Hyaloideoretinal degeneration with anterior chamber angle, facial, dental, and skeletal anomalies.

An autosomal dominant syndrome with Marfan-like features was found in a black pedigree. Eye findings included cataract, lens colobomas, dislocated lenses, myopia, hyaloideoretinal degeneration, and abnormalities of the anterior chamber angles. Facial and dental anomalies included slightly underdeveloped bridge of the nose, protruding maxilla, and dental malocclusions. Selected members of this pedigree showed dolichestenomelia or arachnodactyly or both. Good visual prognosis resulted after (1) cataract or dislocated lens surgery and (2) prophylactic therapy of retinal holes and degeneration.

Lysophosphatidyl choline and cataracts in uveitis.

In aqueous humor from rabbits with uveitis or after anterior chamber paracentesis, the levels of lysophosphatidyl choline (LPC) were 10.2mug/ml and 14.7mug/ml, respectively. These LPC levels induce early cataractous changes in the rabbit lens in culture. Analysis of the fatty acid composition of LPC showed that saturated fatty acids were more predominant in secondary aqueous humor than in primary aqueous humor. In vitro, natural LPC induced more pronounced gains in sodium ions and water by the lens than similar concentrations of synthetic L-alpha-lysopalmitoyl phosphatidyl choline. In contrast to prostaglandin E, the levels of LPC in aqueous humor of rabbits with uveitis are cataractogenic. Thus, LPC or its precursors, rather than prostaglandins, are involved in the production of cataracts in uveitis.

Serous retinal detachments in thrombotic thrombocytopenic purpura.

Serous retinal detachments are a rare ocular complication of thrombotic thrombocytopenic purpura (TTP), with only six previous case reports in the literature. We have recently observed two patients with relapsing TTP who developed bilateral serous retinal detachments during acute exacerbations of their disease. In contrast to all but one of the previously described patients, both of our patients survived the episode during which retinal detachments occurred. Hypertension appears to contribute to the development of retinal detachments in TTP, and vigorous efforts at blood pressure control are indicated. Serous retinal detachments may be a more frequent component of chronic relapsing TTP than has been suspected.

Corticosteroid-induced cataracts.

The association linking corticosteroid therapy with the development of posterior subcapsular cataracts has been well documented. These drugs are widely used therapeutically, principally to capitalize on their ability to inhibit inflammatory responses. The literature on corticosteroid-induced posterior subcapsular cataracts is reviewed here. Data from the previously published series and individual lens susceptibility to corticoids do not allow the establishment of a direct factor relating cataract formation to corticosteroid dose and the duration of therapy; however, significant progress has been made in elucidating the mechanism by which corticoids bring about the development of these opacities. Exploration into the development of these lesions has shed light on the similarities these opacities share with other cataracts, especially with regard to location and pathogenesis.

Congenital varicella cataract.

A 16-month-old boy with 1:16 and 1:8 serum titers to varicella zoster fluorescent membrane antigen had had unilateral cataract and microphthalmos since birth. The mother had suffered varicella during the fourth month of pregnancy. Cataract aspiration in the child was uncomplicated.

The eye in the partial trisomy 2q syndrome.

Mandibulofacial dysostosis, mental retardation, skeletal, genital, and ocular malformations occurred in a family with partial trisomy of the long arm of chromosome 2. Translocations of chromatin material from the long arm of chromosome 2 to the short arm of chromosome 9 was balanced in the female carriers of the pedigree but was unbalanced among the males. Ocular signs in the males included uveal coloboma, anterior chamber angle anomalies as in Ringer's syndrome, congenital glaucoma with dislocated lens, exotropia, and blepharoconjunctivitis. These findings were related to an inherited malformation syndrome.

Aniridia, cataracts, and Wilms' tumor in monozygous twins.

We studied the first instance of aniridia-Wilms' tumor syndrome in twins who were mentally retarded. Both of them had congenital aniridia, cataracts, and glaucoma; only one subsequently developed a Wilms' tumor. A two-allele, two-step mutation is the most likely explanation of this genetically abnormal syndrome in twins. The aniridia-Wilms' tumor syndrome in twins further documents the relationship of teratogenic malformations and neoplasias.

Fabry disease: diagnosis by alpha-galactosidase activities in tears.

The enzymatic diagnosis of hemizygotes with Fabry disease and heterozygous carriers was accomplished by the fluorometric determination of alpha-galactosidase activities in tears. Two components of total alpha-galactosidase activity were differentiated by their relative thermostabilities and by chromatography on DEAE-cellulose. The major component, alpha-galactosidase A, was thermolabile and represented approximately 90% of total activity; the remaining activity was thermostable, eluted at a slightly higher salt concentration and was designated alpha-galactosidase B. A single, symmetric pH optimum was observed for total alpha-galactosidase activities from heterozygotes and normal individuals, whereas the total activity from hemizgotes, which was about 10% of that in normal controls, had a broad pH profile, identical to those for alpha-galactosidase B activities from all individuals studied. The apparent Km values for total activities were 3.2, 4.0, and greater than 13 mM for normal individuals, heterozygotes, and hemizygotes, respectively. In contrast, apparent Km values for alpha-galactosidase B activities were greater than 13 mM for all individuals, further suggesteng that the residual activity in hemizygotes with Fabry disease represented the alpha-galactosidase B component. of the potential inhibitors studied, alpha-D-melibiose was found to competitively inhibit total alpha-galactosidase activity (Ki approximately 10 mM). These studies demonstrate that tears provide an easily obtainable source of freshly secreted enzyme for the diagnosis of hemizygotes and heterozygotes with Fabry disease and suggest that tears may be useful for the diagnosis of other inborn errors of metabolism.

Rise in lens temperature on exposure to sunlight or high ambient temperature.

The effect of increase ambient temperature and sunlight on the temperatures of the rabbit lens and posterior chamber (PC) aqueous humour was measured by needle thermistor probes while the rectal temperature was monitored. Exposure of rabbits to sunlight (35 degrees-42 degrees C), in New Haven, Connecticut, USA, resulted in significant temperature increases in PC (4.3 degrees C), lens (3.2 degrees C), and rectum (2.3 degrees C). Returning animals to the shade resulted in a progressive decrease in the temperatures of the PC or lens in the tested eye, but repeating exposure to sunlight resulted in significant increases of the baseline (PC) temperature (increase 2.68 degrees C) of the second eye. Exposure of rabbits to sunlight at 49 degrees C in Chandigarh, India, resulted in increased PC temperature of 4.48 degrees C after 9 minutes. Increased PC and lens temperatures after exposure to sunlight are due both to an ambient temperature effect through the cornea and to increased body temperature. In dry and hot tropical areas of the world temperature increases in the lens after exposure to sunlight may initiate or accelerate the formation of senile cataracts.

Fate of insulin in the retina: an autoradiographic study.

A system for whole-blood perfusion of the bovine eye through the cilioretinal artery was developed and the distribution and binding of 125I-labelled insulin and human growth hormone (HGH) were studied autoradiographically. Sodium fluorescein was used as a tracer to monitor blood retinal barrier integrity, and electron microscopy was used to determine structural preservation after perfusion fixation. With this system, barrier integrity and structural perservation of both the neural retina and the retinal blood vessels were regularly obtained, with perfusion periods of as long as 5 hours. By quantitative light microscopy autoradiography, insulin binding sites were identified on the endothelial cells of retinal capillaries after perfusion with blood containing 125I-insulin. 125I-insulin binding was competitively inhibited by the addition of unlabelled insulin to the perfusing blood. By contrast the low level of binding of HGH to retinal capillaries was nonspecific. Electron microscopy autoradiography revealed 125I-insulin autoradiographic grains lying over the endothelial cell wall, over pinocytotic vesicles, and over the cytoplasm of both endothelial cells and pericytes. This suggests that, after binding to the cell surface, some insulin passes into the cell cytoplasm. However, neither 125I-HGH penetrated as far as the retina in the periods studied.

Rieger's syndrome with pericentric inversion of chromosome 6.

Pericentric inversion of chromosome 6 (6p+q-) was found in a girl with Rieger's syndrome and in her father. The only ocular signs in the father were prominent iris mounds and Schwalbe's line. The association of chromosomal anomalies with Rieger's syndrome indicates the need for a chromosome banding test in familial or sporadic patients with the syndrome and in patients with mild anomalies of the anterior chamber angle.

Senile cataracts: evidence for acceleration by diabetes and deceleration by salicylate.

A method is described for determining the natural progression of senile cataracts in humans and whether certain factors accelerate or decelerate this progression. The method consists in plotting the age of the patient against the degree of opacity of the cataract to find the regression relation. A comparison of cataracts from diabetic and nondiabetic patients revealed that diabetes accelerated senile cataract formation, so that there was a difference of 9.6 years in the age of the two groups with more dense cataracts. Plasma tryptophan levels, which are increased in cataract patients, are lowered by acetylsalicylic acid (ASA). In this study ASA decelerated cataract formation in diabetic and nondiabetic patients. Among the nondiabetic patients cataract formation in a group with osteoarthritis was delayed by an average of 10 years. Deceleration of cataract formation resulting from ASA administration may reduce the need for surgical removal of cataracts.