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Modulation of growth in retina-derived cells by extracellular matrices
1Department of Ophthalmology, Medical College of Wisconsin, Milwaukee 53226.
Abstract:
Intravitreal membranes from patients with proliferative vitreoretinopathy (PVR) consist partly of retinal glial (RG) and retinal pigment epithelial (RPE) cells surrounded by varying amounts of extracellular matrix (ECM). The contribution of the ECM to the growth of PVR membranes is unknown. This study was undertaken to determine if proliferation in cultured RPE and RG cells is affected by different substrates, including some ECM materials which have been identified in PVR membranes. Substrates tested included type I collagen, basement membrane Matrigel, and poly-D-lysine, as well as uncharacterized cell type-specific matrices deposited by cultured RPE and RG cells. Proliferation was quantified by 3H-thymidine incorporation and radioautography 24 hours after plating and by cell counts after 14 days in the presence of serum. Relative to uncoated culture plastic, growth of RPE cells was inhibited by Matrigel, enhanced by poly-D-lysine, and unaffected by type I collagen. In contrast, growth in RG cells was inhibited by type I collagen and unaffected by the other substrates. Analysis of the timing of DNA synthesis after plating suggested that the substrates which affected RPE growth did so by altering the fraction of cycling cells rather than the cell cycle time. For the cell-derived matrices, heterotypic matrix (matrix produced by the other retinal cell type) enhanced the growth of both RPE and RG. The results suggest that the ECM may modify the growth of cells contributing to PVR membranes. Of note is that the cell-derived matrices reciprocally stimulated growth of RG and RPE cells, cell types which may interact in PVR membranes.
Insights
Extracellular matrix (ECM) components influence retinal glial (RG) and retinal pigment epithelial (RPE) cell proliferation. Cell-derived matrices reciprocally stimulate RG and RPE cell growth, suggesting a role for ECM in proliferative vitreoretinopathy (PVR) membrane development.
Area of Science:
- Ophthalmology
- Cell Biology
- Biochemistry
Background:
- Proliferative vitreoretinopathy (PVR) involves intravitreal membranes composed of retinal glial (RG) and retinal pigment epithelial (RPE) cells embedded in extracellular matrix (ECM).
- The specific role of ECM in the proliferation of cells within PVR membranes remains largely undetermined.
Purpose of the Study:
- To investigate the impact of various substrates, including ECM components found in PVR membranes, on the proliferation of cultured RPE and RG cells.
- To determine if ECM influences cell growth by affecting cell cycle dynamics or the proportion of cycling cells.
Main Methods:
- Cultured RPE and RG cells were plated on substrates including type I collagen, Matrigel, poly-D-lysine, and cell-specific matrices.
- Cell proliferation was assessed using 3H-thymidine incorporation, radioautography, and direct cell counts.
- DNA synthesis timing was analyzed to understand substrate effects on cell cycle parameters.
Main Results:
- Matrigel inhibited RPE cell growth, while poly-D-lysine enhanced it; type I collagen had no effect on RPE cells.
- Type I collagen inhibited RG cell growth, with no significant effect from other tested substrates.
- Cell-derived matrices, particularly heterotypic matrices, reciprocally enhanced the proliferation of both RPE and RG cells.
Conclusions:
- The extracellular matrix (ECM) can modulate the proliferation of retinal glial (RG) and retinal pigment epithelial (RPE) cells.
- Cell-derived matrices play a significant role in stimulating the growth of RG and RPE cells, suggesting their importance in the pathogenesis of proliferative vitreoretinopathy (PVR).