Differing effects of dexamethasone and diclofenac on posterior capsule opacification-like changes in a rat lens explant model.
Posterior capsular opacification (PCO) arises from lens cells that remain associated with the lens capsule after cataract surgery and subsequently become abnormal, proliferate and migrate into the visual pathway. In this study, a rat lens explant model was used to assess the effects of the prototype steroidal and non-steroidal anti-inflammatory drugs, dexamethasone (DEX) and diclofenac (DIC), on epithelial cells undergoing PCO-like changes. Such drugs are widely used at the time of cataract surgery. TGFbeta2 and FGF-2 were added sequentially and explants were cultured for up to 30 days, with or without addition of DEX or DIC at a clinically relevant concentration. Without DEX or DIC, explants became multilayered and cells tended to retract into PCO-like plaques. Inclusion of DEX, but not DIC, resulted in transient formation of needle-like cells, enhanced cell coverage, and the retention a monolayer of migratory cells surrounding PCO-like plaques. With or without drug addition, most cells became aberrant, as indicated by loss of Pax6 expression and the presence of PCO markers alpha-smooth muscle actin and type I collagen; however, DEX and DIC both strongly enhanced type I collagen accumulation. Furthermore, DEX enhanced cell coverage in explants treated with TGFbeta alone. Thus the behaviour of lens cells was significantly and differentially affected by the presence of DEX and DIC, highlighting the possibility that drugs used to control inflammation after cataract surgery, and the clinician's choice of drugs, may influence PCO development.
Symonds
Joel G
JG
Discipline of Anatomy and Histology and Institute for Biomedical Research, F13, University of Sydney, Sydney, NSW 2006, Australia.
Lovicu
Frank J
FJ
Chamberlain
Coral G
CG
D000199:Actins / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002386:Cataract / Q000473:pathology*; D048430:Cell Shape / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005136:Eye Proteins / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000378:metabolism; D007903:Lens Capsule, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012097:Repressor Proteins / Q000378:metabolism; D046509:Tissue Culture Techniques; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000199:Actins; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D024042:Collagen Type I; D003907:Dexamethasone; D004008:Diclofenac; D005136:Eye Proteins; D016222:Fibroblast Growth Factor 2; D005938:Glucocorticoids; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011994:Recombinant Proteins; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta; C000605733:Pax6 protein, rat; C498862:Acta2 protein, rat