Effects of dexamethasone on posterior capsule opacification-like changes in a rat lens explant model.
OBJECTIVE
Many patients whose sight is initially restored by cataract surgery eventually suffer secondary loss of vision because of posterior capsule opacification (PCO; after-cataract), a condition in which lens epithelial cells left behind at surgery become aberrant and migrate into the light path. The aim of this study was to determine whether dexamethasone (DEX), an anti-inflammatory agent widely used before and after cataract surgery, influences the behavior of lens cells under conditions relevant to PCO development.


METHODS
An established rat PCO model was used in which explanted epithelial cells attached to the lens capsule are exposed sequentially to TGFbeta2 and FGF-2. Cultures with or without DEX (100 nM), and appropriate controls, were maintained for up to 30 days and assessed by light and scanning electron microscopy or immunolocalization of PCO markers (alpha-smooth muscle actin or fibronectin) or a marker for lens epithelial cell phenotype (Pax-6).


RESULTS
In the absence of DEX, explants become multilayered and plaques that express PCO markers form. Cells tend to gather up into the plaques, leaving the surrounding lens capsule denuded. Changes in lens cell behavior with addition of DEX included rapid formation of long, needle-like cells, less extracellular matrix deposited on explant surface, and plaques surrounded by a monolayer of migratory cells. Immunolocalization confirmed that the latter were not normal lens epithelial cells.


CONCLUSIONS
Lens cell behavior in this PCO model was significantly affected by inclusion of DEX, highlighting the possibility that its use as an anti-inflammatory at the time of cataract surgery may influence PCO development.
Department of Anatomy and Histology and Institute for Biomedical Research, The University of Sydney, New South Wales, Australia.
Kylie J
KJ
Mansfield
Anna
A
Cerra
Coral G
CG
Chamberlain
D000199:Actins / Q000378:metabolism; D000818:Animals; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005136:Eye Proteins; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005938:Glucocorticoids / Q000633:toxicity*; D018398:Homeodomain Proteins / Q000378:metabolism; D007903:Lens Capsule, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008858:Microscopy, Phase-Contrast; D008954:Models, Biological; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053781:Transforming Growth Factor beta2
D000199:Actins; D005136:Eye Proteins; D005353:Fibronectins; D005938:Glucocorticoids; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605733:Pax6 protein, rat; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D016222:Fibroblast Growth Factor 2; D003907:Dexamethasone