Pharmakologische Ansätze zur Prävention der Cataracta secundaria

Abstract

Secondary cataract or posterior capsule opacification (PCO) is still the most frequent long-term complication of cataract surgery. Tremendous advances have been made, especially during the last 10 to 15 years, in terms of surgical techniques and improvement of implant technology. However, the problem of proliferation and migration of lens epithelial cells (LECs) postoperatively has not yet been solved completely although we know that a sharp optic edge of intraocular lenses (IOL) combined with hydrodissection, complete overlapping of capsulorhexis and IOL-optic as well as capsular bending reduce PCO formation significantly. In the 1980 s, investigators like Hartmann et al. began with the application of pharmacological substances in-vitro in order to successfully prevent LECs from proliferating and migrating. Cytostatic drugs, steroids, non-steroidal antiphlogistics, adhesion inhibitors, heparin, lidocaine, suramin, immunotoxins, photodynamic therapy and osmotic effective solutions were tested. In several studies different drug delivery systems were investigated in order to provide a longer and more effective impact on LECs. However, the in-vivo use has been viewed critically since the selective targeting of LECs was not possible and serious damage to the surrounding tissue had to be considered. Recently, the development of the PerfectCapsule System for vacuum-sealed capsule irrigation allows the selective targeting of LECs inside the capsular bag. This survey gives an update on past, current and future means and trends to reduce or prevent PCO formation pharmacologically.

TGF-β2 induces epithelial-mesenchymal transition in cultured human lens epithelial cells through activation of the PI3K/Akt/mTOR signaling pathway

“…At present, pharmacological PCO prophylaxis has not been achieved ( 23 ). Although several approaches have been developed to prevent PCO using chemicals, none of these apporaches have been applied in a clinical setting ( 24 – 26 ). The results of the present study demonstrated that LY294002 and other PI3K/Akt/mTOR signaling pathway inhibitors, including rapamycin and Ku-0063794, may be potential agents for the prevention and treatment of PCO.…”

Prevention of Lens Epithelial Cell Growth In Vitro Using Mibefradil-Containing PLGA Micro Particles~!2008-04-23~!2008-05-24~!2008-06-12~!

“…To interfere only with the outgrowing, proliferating cells is an important feature for the protection of the intact collateral tissue in the eye [9] and offers possibilities in the specifically pharmacological intervention in the secondary cataract. Until now the use of pharmacological substances like cytostatic drugs and immunotoxins has been limited because of damages also of the surrounding tissues due to general toxic effects [35-37]. Mibefradil as T-channel inhibitor interfered especially with growing HLE-B3 cells expressing higher Ca v 3.1 and 3.3 levels [17].…”

Capsular tension ring–based in vitro capsule opacification model

“…[1][2][3] Besides IOL material 4,5 and design, 6-8 major emphasis of PCO prevention focuses on the development of antiproliferative and cytotoxic lens epithelial cell (LEC)-manipulating substances. [9][10][11][12] Because of possible cell toxicity, it is usually difficult to test new substances and strategies that influence LEC growth in humans. Thus, there is considerable interest in developing in vitro organ culture models for PCO.…”