Gene expression and discovery during lens regeneration in mouse: regulation of epithelial to mesenchymal transition and lens differentiation.
OBJECTIVE
It has been shown that after extracapsular lens removal by anterior capsulotomy in the mouse, the lens can be regenerated. However, as the capsular bag is filled with fibers, epithelial to mesenchymal transition (EMT), an event which is common after cataract surgery as well, takes place during early stages. This study, using a unique mouse model, was undertaken to identify novel regulators and networks in order to more clearly understand secondary cataracts at the molecular level.


METHODS
We examined global gene expression via microarray analysis of mouse lens regeneration after extracapsular surgery. Gene expression at different times after surgery was correlated with the processes of EMT, which is seen in the initial stages of regeneration, and lens fiber differentiation, which occurs later.


RESULTS
Several notable patterns were observed from the gene clustering data. It was obvious from the analysis that initially there is a response to injury, extensive matrix remodeling, and severe downregulation of genes encoding lens structural proteins. The patterns returned gradually to normal three weeks after surgery. New genes were identified from the clustering results that might be potential regulators of EMT and lens differentiation.


CONCLUSIONS
With this approach, we demonstrated the utility of a mouse model to study secondary cataracts at the molecular level. Extension of these studies in mice with known mutations affecting EMT or lens differentiation should allow the identification of the crucial molecular players that could lead to better treatments of secondary cataracts.
Medvedovic
Mario
M
Department of Environmental Health, Center for Environmental Genetics, University of Cincinnati Medical School, Cincinnati, OH, USA.
Tomlinson
Craig R
CR
Call
Mindy K
MK
Grogg
Matthew
M
Tsonis
Panagiotis A
PA
D000818:Animals; D002386:Cataract / Q000209:etiology; D003199:Computer Systems; D003459:Crystallins / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000503:physiopathology; D005136:Eye Proteins / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D007908:Lens, Crystalline / Q000378:metabolism / Q000503:physiopathology*; D008648:Mesoderm; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D013997:Time Factors
D003459:Crystallins; D005136:Eye Proteins; D012333:RNA, Messenger