A critical appraisal of the etiology of adult human lenticular opacification and an investigation into the role of metabolic factors in its pathogenesis

[摘要] ENGLISH ABSTRACT:The eye is that biological instrument which conveys the light of the external world into the inner world of themind, wherein we receive the miraculous gift of vision. So precious is this gift, that Science must search forways to keep this portal clear for the flow of light. Indeed, Science is called upon to 'make war upon the bloodytyrant, Time. (Shakespeare W. Sonnet No. 16). For, in the course of ageing, the lens grows cloudy andcataractous. In this battle between Science and Time, we are fortunate to live in an era in which Science isuncovering the molecular basis for the various obstacles to vision. The question arises, whether or not, theruinous hand of time can be stayed.Due to unrelenting, progressive lens opacification, most of the elderly are destined to be subjected to loss ofvision and with passage of time, even blindness. Globally the cataract surgery rate is inadequate to keep pacewith the ever growing demand on financial and human resources created by the cataract problem. An immensechallenge therefore is directed to primary eye care: 'Can cataract be prevented or can its onset at least bepostponed?This laudable ultimate aim can only be achieved once the etiology of cataractogenesis is well understood. Thisdissertation seeks to examine two previously unrecognized etiological aspects that, if correctly understood andmanaged, have the potential to achieve preventive ophthalmological goals that may indeed help to stay the'ruinous hand of time'.The first aspect deals with the role of lipids and was examined using a study group of dyslipidemic subjects. Thefirst part of the study concluded that dyslipidemic patients develop cortical lens opacities more frequently and atan earlier age than the normal population, and that cortical lens opacities should be regarded as one of the mostreliable clinical signs of dyslipidemia. Furthermore, an extremely strong correlation was found to exist betweenlow HDL Cholesterol levels and the development of opacities. Below a HDL-Cholesterol level of 1,5mmol/l,subjects had more than seven-fold higher risk of falling in the lens opacity subgroup than those with HDLCholesterollevels above 1,5mmol/l. An equally strong correlation was demonstrated between high (>5)LDLHDL ratios and the development of lens opacities. Subjects with a LDL:HDL-C ratio below 5 possessed a2.35 times greater risk of having lenticular opacities than the group with a LDL:HDL-C ratio greater than 5. Theprevention or retardation of dyslipidemia associated lens opacities is therefore possible, provided patients with agenetic predisposition are detected early and their blood lipids managed adequately.The second aspect deals with the relationship between age related cataracts and the acetylation status of theindividual. This study compellingly submits that the slow acetylator pheno- and genotype may be regarded as agenetic indicator of risk for age related cataract. The ability accurately to classify a patient genotypically andphenotypically, may henceforth be useful in health counseling since, if an individual is identified as being a slow acetylator, additional preventative and precautionary measures may be taken, i.e. the prevention of UVexposureto the eye and caution with the ingestion of xenobiotics like caffeine, commercial dyes, foodpreservatives, and drugs. Furthermore, such a finding should be taken into account in the long term therapeuticmanagement of glaucoma, with special regard to carbonic anhydrase inhibitors which are sulphonamide-relateddrugs and totally dependent on the N-acetyltransferase pathway for metabolism. These drugs may accumulatein the slow acetylator over time and exert toxic effects intra-ocularly, conceivably including cataractogenesis.The search for genetic and metabolic mechanisms that may contribute to human cataractogenesis should bepursued with great enthusiasm. This endeavour may help Science to achieve its primary objective, ablate theeffects of Time and really aid in preventing cataracts in man.

[发布机构] Stellenbosch University