salicylates and Cataract

Research into the biological basis of lens transparency has demonstrated the implication of lens sugar stress in the diabetic cataract whereas senile cataract is the result of natural degeneration which is enhanced by various external factors such as cosmic and ionizing rays, or oxidative processes. Drugs have been developed which are aimed at being effective on lens pathological physiology and metabolism, concurrently. Such molecules: aldose reductase inhibitors (ARIs: sorbinil, AD-5467, CT-112 and imirestat), acetyl salicylic acid (ASA), salicylate (SA) and sodium monomethyl trisilanol orthohydroxybenzoate (SMB, a prodrug for salicylate) have undergone pharmacodynamic, pharmacokinetic and/or clinical studies which are presented here. ARIs have shown efficacy in slowing down and preventing the progression of experimental sugar cataracts; sorbinil can partially reverse the very early morphological signs of sugar cataract. Sorbinil and imirestat have also demonstrated anti-oxidant properties. ARIs administration (per os or by topical instillation) generally results in lens levels compatible with concentrations that are efficient on biochemical mechanisms of cataract formation. However, at the present time, clinical evaluations are in progress and as yet, there is no confirmation of their efficacy in man. ASA and SA can prevent various mechanisms of lens protein denaturation; they inhibit AR and prevent, in vitro, the formation of some pigments found in the aged cataractous lens. Extrapolation of the ASA ocular pharmacokinetics results in animal to man, suggest that ASA administration per os could result in efficacious levels in the lens. This is also sustained by the observation of a reduced frequency of cataracts in ASA treated diabetic rheumatoid arthritis patients. SMB pharmacokinetic studies have shown small but persistent levels of the active principle in the lens. They suggest that the capsule slows down SA diffusion into the lens and that, on the contrary, lens epithelium facilitates its penetration. Preliminary results of pharmacodynamic studies are given.

Topics: Aldehyde Reductase; Animals; Cataract; Humans; Lens, Crystalline; Salicylates

Topics: Administration, Topical; Aged; Aged, 80 and over; Cataract; Double-Blind Method; Female; France; Humans; Lens, Crystalline; Male; Middle Aged; Ophthalmic Solutions; Organosilicon Compounds; Salicylates

Alzheimer disease is characterized by cerebral Abeta deposition, which we have recently discovered occurs also in the lens as cataracts in Alzheimer disease patients. Here we report the presence of significantly increased cataracts in the lenses of an Abeta-transgenic mouse model for Alzheimer disease and their amelioration upon treatment with EUK-189, a synthetic SOD/catalase mimetic. These data support an oxidative etiology for AD-associated lens cataracts and their potential to be treated preventatively with antioxidants.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Catalase; Cataract; Free Radicals; Humans; Mice; Mice, Transgenic; Models, Chemical; Organometallic Compounds; Oxygen; Salicylates; Superoxide Dismutase

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.

Topics: Animals; Aqueous Humor; Aspirin; Cataract; Crystallins; Diabetes Complications; Galactose; Humans; Lens, Crystalline; Rabbits; Rats; Salicylates; Sodium Salicylate; Vitreous Body

Topics: Adrenal Cortex Hormones; Arthritis; Arthritis, Rheumatoid; Blindness; Cataract; Conjunctivitis; Diplopia; Drug Therapy; Edema; Eye Diseases; Eye Manifestations; Glaucoma; Gold; Humans; Iatrogenic Disease; Intraocular Pressure; Iridocyclitis; Iritis; Keratitis; Lupus Erythematosus, Systemic; Myopia; Rheumatic Diseases; Salicylates; Spondylitis; Spondylitis, Ankylosing; Toxicology; Uveitis

Topics: Adolescent; Arthritis; Arthritis, Juvenile; Atropine; Cataract; Child; Cocaine; Corneal Opacity; Cortisone; Eye; Humans; Iridocyclitis; Penicillins; Prednisolone; Salicylates