Thesis (PhD)--Stellenbosch University, 2001 / ENGLISH ABSTRACT: The eye is that biological instrument which conveys the light of the external world into the inner world of the
mind, wherein we receive the miraculous gift of vision. So precious is this gift, that Science must search for
ways to keep this portal clear for the flow of light. Indeed, Science is called upon to “make war upon the bloody
tyrant, Time.” (Shakespeare W. Sonnet No. 16). For, in the course of ageing, the lens grows cloudy and
cataractous. In this battle between Science and Time, we are fortunate to live in an era in which Science is
uncovering the molecular basis for the various obstacles to vision. The question arises, whether or not, the
ruinous hand of time can be stayed.
Due to unrelenting, progressive lens opacification, most of the elderly are destined to be subjected to loss of
vision and with passage of time, even blindness. Globally the cataract surgery rate is inadequate to keep pace
with the ever growing demand on financial and human resources created by the cataract problem. An immense
challenge therefore is directed to primary eye care: “Can cataract be prevented or can its onset at least be
postponed?”
This laudable ultimate aim can only be achieved once the etiology of cataractogenesis is well understood. This
dissertation seeks to examine two previously unrecognized etiological aspects that, if correctly understood and
managed, 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. The
first part of the study concluded that dyslipidemic patients develop cortical lens opacities more frequently and at
an earlier age than the normal population, and that cortical lens opacities should be regarded as one of the most
reliable clinical signs of dyslipidemia. Furthermore, an extremely strong correlation was found to exist between
low 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 HDLCholesterol
levels 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 a
2.35 times greater risk of having lenticular opacities than the group with a LDL:HDL-C ratio greater than 5. The
prevention or retardation of dyslipidemia associated lens opacities is therefore possible, provided patients with a
genetic 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 the
individual. This study compellingly submits that the slow acetylator pheno- and genotype may be regarded as a
genetic indicator of risk for age related cataract. The ability accurately to classify a patient genotypically and
phenotypically, 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 UVexposure
to the eye and caution with the ingestion of xenobiotics like caffeine, commercial dyes, food
preservatives, and drugs. Furthermore, such a finding should be taken into account in the long term therapeutic
management of glaucoma, with special regard to carbonic anhydrase inhibitors which are sulphonamide-related
drugs and totally dependent on the N-acetyltransferase pathway for metabolism. These drugs may accumulate
in 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 be
pursued with great enthusiasm. This endeavour may help Science to achieve its primary objective, ablate the
effects of Time and really aid in preventing cataracts in man. / AFRIKAANSE OPSOMMING: Die wondergawe van visie word vir ons moontlik gemaak deur die oog wat as biologiese instrument die lig van
die buitewereld inlaat na die binnewereld van die brein. So kosbaar is hierdie gawe dat die Wetenskap
deurgaans moet poog om die poort oop te hou. Inteendeel, die Wetenskap word gemaan deur Shakespeare in
sy Sonnet nommer 16 om “oorlog te maak teen die bloeddorstige tiran, Tyd”. Soos ‘n mens ouer word, word die
lens dof en ‘n katarak mag vorm. Ten spyte van hierdie stryd tussen ‘Wetenskap’ en ‘Tyd’ leef ons in die
gelukkige era waarin die Wetenskap meer en meer leer van die verskeie obstruksies tot visie. Die vraag
ontstaan of die rinnewerende hand van ‘Tyd’ gestuit sal kan word.
Vanwee ongenaakbare, progressiewe lensvertroebeling is die meeste bejaardes bestem om aan visie verlies, en
met verloop van tyd selfs blindheid, te ly. Die wereldwye katarakchirurgie tempo is nie voldoende om by te hou
by die immergroeiende finansiele en mannekrag eise wat deur die katarak probleem gestel word nie. Daar word
dus ‘n reuse uitdaging aan primere oogsorg gestel naamlik: “Kan katarakte nie eerder voorkom of die aanvang
daarvan ten minste uitgestel word nie?”
Hierdie prysenswaardige doelwit kan nie bereik word alvorens die etiologie van kataraktogenese goed verstaan
word nie. Hierdie tesis ondersoek twee voorheen onerkende etiologiese aspekte wat, indien hulle korrek
verstaan en hanteer word, beslis die potensiaal het om die gemelde voorkomende doelwitte te bereik en sekerlik
te kan bydrae om die rinnewerende hand van Tyd te stuit.
Die eerste aspek spreek die rol van lipiede aan deur te kyk na 'n studiegroep van dislipidemiese persone. Die
eerste deel van die studie kom tot die gevolgtrekking dat dislipidemiese pasiente kortikale lens opasiteite meer
dikwels en op ‘n vroeer ouderdom ontwikkel as die normale populasie en dat sulke opasiteite beskou moet word
as een van die mees betroubare kliniese tekens van dislipidemie. Daar is ook ‘n baie sterk korrelasie gevind
tussen lae HDL cholesterol vlakke en die voorkoms van opasiteite. Persone in die studie met ‘n HDL cholesterol
vlak laer as 1,5mmol/l het ‘n sewe keer hoer kans gehad om in die lensopasiteit subgroep te val as die met ‘n
HDL cholesterol vlak laer as 1,5mmol/l. ‘n Sterk korrelasie tussen ‘n hoe (>5) LDLHDL verhouding en die
voorkoms van lens opasiteite is ook gevind. Persone met ‘n LDLHDL verhouding >5 het ‘n 2.35 maal groter
risiko gehad om lensopasiteite te he as die met ‘n LDL:HDL verhouding van <5. Die voorkoming of vertraging
van dislipiedemie geassosieerde lens opasiteite is dus moontlik, solank persone met ‘n genetiese geneigdheid
daartoe vroeg ontdek en hulle bloedlipiede voldoende beheer word.
Die tweede deel van die tesis handel oor die verhouding tussen ouderdoms verwante katarakte en die asetilasie
status van die individu. Met oortuiging kom hierdie studie tot die gevolgtrekking dat die stadige asetilator fenoen
genotipe as 'n genetiese merker vir ouderdoms verwante katarakte beskou moet word. Die vermoe om ‘n
individu beide genotipies en fenotipies akkuraat te klassifiseer mag voorts bruikbaar wees in
gesondheidsraadgewing. Indien ‘n individu geTdentifiseer is as ‘n stadige asetileerder, kan addisionele voorsorg
maatreels getref word soos bv. die voorkoming van blootstelling van die oog aan UV lig sowel as omsigtigheid
met die inname van xenobiotika soos kaffei'ene, kleurstowwe, voedsel preserveermiddels en geneesmiddels.
Hierdie bevinding moet ook in berekening gebring word in die langtermyn terapeutiese hantering van gloukoom.
Die koolsuuranhidrase inhibitore, dikwels gebruik in die behandeling van gloukoom, is sulfonamied-agtige
middels en dus totaal afhanklik van die N-asetieltransferase pad vir hulle metabolisme. Hierdie middels kan
ophoop in die stadige asetileerder en gegewe genoeg tyd, bes moontlik toksiese intra-okulere effekte tot gevolg
he.
Die soeke na genetiese en metaboliese meganismes wat mag bydra tot menslike kataraktogenese behoort
nagestreef te word met groot entoesiasme. Hierdie strewe mag dalk net vir die 'Wetenskap' bystaan om sy
primere mikpunt te bereik, die effek van ‘Tyd’ te neutraliseer en te help om katarakte werklik te voorkom.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/52069 |
| Date | 12 1900 |
| Creators | Meyer, David |
| Contributors | Parkin, D. P., Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Surgical Sciences. Ophthalmology. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | Unknown |
| Type | Thesis |
| Format | 138 p. : ill. |
| Rights | Stellenbosch University |
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