Protein-Kondensationskrankheiten - Molekulare Mechanismen bei der Kataraktogenese[1] [2]

Zusammenfassung

Die Kataraktogenese des normalen, alternden Auges kann durch eine kontinuierliche Zunahme von Streulicht erklärt werden, das die alternde Linse abstrahlt. Diese Zunahme ist eine Exponentialfunktion des Alters, deren Zeitkonstante im Durchschnitt 35 Jahre beträgt. Ein entscheidender Faktor dieses Streulichtes ist die Kondensation von Molekülen zu Aggregaten. Aggregationszustände sind indessen auch die Hauptursache einer breiten Klasse von „Kondensationskrankheiten”, die die Spätfolgen des Diabetes mellitus, der Alzheimerschen Krankheit und anderen einschließen. Es wird hier eine vereinfachte Darstellung der Mechanismen dieser Krankheiten und eine daraus folgende Strategie zu deren Bekämpfung gegeben. Im Falle der menschlichen Katarakt müsste ein Inhibitor, um als wirksam zu gelten, im Durchschnitt die Zeitkonstante von etwa 20 % oder mehr vergrößern.

There are reasons to classify a number of apparently disparate diseases as “condensation” (or molecular aggregation) diseases. Examples of such condensation diseases include the late phase of diabetes mellitus, Alzheimer's disease and others. With an expanding knowledge, the list of these diseases is likely to increase. We shall describe the underlying common mechanisms, the aim being to find anticataractogenic drugs based on this insight. The common, most important denominator of various clinically differing condensation diseases derives from the interaction of the macromolecules which is in part attractive and in part repulsive. Aggregation resp. clumping of the macromolecules of the cristalline lens, the reasons for light scattering, may be prevented by introducing a number of molecules of various designs into the original macromolecular complex which reduce the tendency of aggregation. Cataract inhibitors of this category may be regarded as effective if they are able to increase the time constant of the normal aging process (i.e. the increment of scatter) by about 20 % .

Schlüsselwörter

Kataraktogenese - Makromoleküle - Streulichtmechanismen - Kältekatarakt

Key words

Cataractogenic mechanisms - cold cataract - macromolecules

1 Herrn Prof. Dr. Balder Gloor gewidmet.

2 Manuskript eingereicht am 26. 7. 99 und in der vorliegenden Form angenommen.

Literatur

1 Herrn Prof. Dr. Balder Gloor gewidmet.

2 Manuskript eingereicht am 26. 7. 99 und in der vorliegenden Form angenommen.

• 01 Ansari  R R, Datiles III  M B, King  J F, Leftwood  D. Measuring lens opacity: combining quasi-elastic scattering with Scheimpflug imaging system.  Proc SPIE. 1998;  3246 35-42
• 02 Ansari  R R,  Suh K I. Dynamic light scattering particle size measurement in turbid media.  Proc SPIE. 1998;  3251 146-156
• 03 Benedek  G B, Chyla  L T Jr, Libondi  T, Magante  P, Pennet  M. Quantitative detection of the molecular changes associated with early cataractogenesis in the human lens using quasielastic light scattering.  Curr Eye Res. 1987;  6 1421-1432
• 04 Clark  J I, Benedek  G B. The effects of glycolaldehyd and acrylamid in phase separation and opacification in the calf lens.  Invest Ophthalmol Vis Sci. 1980;  19 771-776
• 05 Clark  J I, Livesey  J C, Steele  J E. Delay or inhibition of rat lens opacification using panthetine and WR-77913.  Exp Eye Res. 1996;  62 75-84
• 06 Friberg  G, Pande  J, Ogun  O, Benedek  G B. Panthetine inhibits the formation of high Tc protein aggregates in g B crystallin solution.  Curr Eye Res. 1996;  15 1182-1190
• 07 Hiraoka  T, Clark  J I. Inhibition of lens opacification during the early stages of cataract formation.  Invest Ophthalmol Vis Sci. 1995;  36 2550-2555
• 08 Hiraoka  T, Clark  J I, Li  X Y, Thurston  G M. Effect of selected anticataract agents on opacification in the selenite cataract model.  Exp Eye Res. 1996;  62 11-19
• 09 Jedziniak  J A, Kinoshita  JH, Yates  E M, Hocker  L O, Benedek  G B. On the presence and mechanism of formation of heavy molecular weight aggregates in human normal and cataractous lenses.  Exp Eye Res. 1973;  15 185-192
• 10 Kinoshita  J H, Kador  P, Datiles  M B. Aldose reductase in diabetic cataract.  JAMA. 1981;  246 257-261
• 11 Könz  F, Ricka  J, Frenz  M, Fankhauser II  F. Dynamic light scattering in the vitreous: Performance of the single-mode fiber technique.  Opt Engineering. 1995;  34 2390-2395
• 12 Pande  J, Lomakin  A, Fine  B, Ogun  O, Sokolinski  I, Benedek  G B. Oxidation of the γ II crystallin solutions yields dimers with pass phase separation temperature.  Proc Natl Acad Sci USA. 1995;  92 1067-1071
• 13 Pande  J, Ogun, Nath  C, Benedek  G B. Suppresion of phase separation in bovine γ IV crystallin solutions: Effect of modification by charged vs uncharged polar groups.  Exp Eye Res. 1993;  57 257-264
• 14 Rovati  L, Fankhauser II  F. Design and performance of a new ophthalmic instrument for dynamic light scattering in the human eye.  Rev Sci Instrum. 1996;  67 2615-2620
• 15 Rovati  L, Fankhauser II  F, Ricka  J. A non invasive instrument for in vivo dynamic light scattering measurment in the human eye. Proc IEEE-EMBC Press 1995: 10-11
• 16 Rovati  L, Fankhauser II  F, Ricka  J. Dynamic light scattering spectroscopy of in vivo human vitreous.  Proc SPIE. 1995;  2632 73-78
• 17 Sebag  J. Structure of the vitreous. In: Sebag J. The Vitreous. Springer Verlag, Heidelberg; 1989: 35-71
• 18 Thurston  G M, Hayden  D L, Burrows  P et al. Quasielastic light scattering study of the living human lens as a function of age.  Curr Eye Res. 1997;  16 197-207