Pharmacological Treatment Strategies in Age-Related Cataracts

Abstract

Cataract is the major cause of blindness worldwide and at present the only approved treatment in many countries including the UK and USA is surgical removal of the lens. In other countries various anti-cataract drugs are available without proof of their efficacy. Research is continuing into the possible benefits of several groups of drugs and some vitamins. The first to be studied were sorbitol-lowering agents (aldose reductase inhibitors) based on the sorbitol hypothesis for diabetic cataract. Sorbitol-lowering agents have distinct effects in vitro and many of them delay the development of cataract in galactose-fed rats. A few delay cataract in diabetic rats but none have been proved effective in clinical trials, although these continue. Aspirin, paracetamol (acetaminophen) and ibuprofen delay diabetic cataract in rats, and have been shown to delay other experimental cataracts. Case-control studies from 3 continents indicate that these drugs, or at least aspirin, protect against cataract. Results of studies on all 3 drugs indicate a benefit even at low doses. Population-based studies did not identify any protection against early lens opacities but tiny opacities that do not impair vision are not a problem. Bendazac protects lens proteins in vitro and delays cataractogenesis in x-irradiated rats. In humans, it reached the clinical trial stage but most trials have been small and with subjective criteria of opacification. One objectively monitored trial suffered from a high drop-out rate. Other preparations studied less extensively include vitamins, aminoguanidine to prevent protein cross-linking in diabetes and agents designed to boost glutathione levels. It is probable that some agents which may delay or prevent cataract will be proved effective soon, and in the end there may be different drugs to delay cataract in different high risk groups. This is what might be expected of a multifactorial disease, although compounds that intervene in the final common pathways to cataract could have a broad efficacy.

Comparative Proteome Analysis of Splenic Lymphocytes in Senescence-Accelerated Mice

“…The higher content of aldose reductase in old people may be involved in many polyol metabolism-related diseases. At present, sorbitol-lowering agents are commonly used to inhibit the synthesis of sorbitol in the treatment of cataracts [59] .…”

Anti-cataract activity of Pterocarpus marsupium bark and Trigonella foenum-graecum seeds extract in alloxan diabetic rats

“…Sorbitol-lowering agents were shown to delay cataract development in galactose-fed rats but were ineffective in clinical trials (Harding, 1992). Lycopene (a potent anti-oxidant but not anti-hyperglycemic agent obtained from tomatoes) also afforded protective effect in the galactose model of cataract but not in hyperglycemic Sand rats (Pollack et al, 1999).…”

“…Aldose reductase inhibitors were shown to delay development of experimental cataract (Costantino et al, 1999), but their toxicity led to failure in reaching clinical stage. In a multi-factorial disease like diabetic cataract, compounds that can reverse/inhibit various common pathways in development of cataract are more likely to succeed (Harding, 1992). In recent years, the role of alternative therapeutic approaches has become very popular (Narayana and Dobriyal, 2000) and since a single plant may have many pharmacological activities (anti-diabetic, anti-oxidant and anti-stress activity) they can be effectively utilized to delay or counter diabetic complications, such as cataract.…”

Green Tea <i>(Camellia sinensis)</i> Protects against Selenite-Induced Oxidative Stress in Experimental Cataractogenesis

“…Oxidative damage to lens epithelium and consequent shift in the antioxidant status of the lens has been considered as one of the common step in cataractogenesis [24]. Maintenance of lens morphology and transparency through modulation of various enzymatic and nonenzymatic defense systems is also reported in Gupta/Halder/Srivastava/Trivedi/Joshi/ Varma experimental cataract [25]. A protection by nutritional antioxidant vitamin C against selenite-induced opacities in young rats gave impetus to cataract prevention studies, and several synthetic and natural agents were subsequently evaluated for their anticataract potential in animals.…”