ABSTRACT
The effects of randomness, an unavoidable feature of intracellular environments, are observed at higher hierarchical levels of living matter organization, such as cells, tissues, and organisms. Additionally, the many compounds interacting as a well-orchestrated network of reactions increase the difficulties of assessing these systems using only experiments. This limitation indicates that elucidation of the dynamics of biological systems is a complex task that will benefit from the establishment of principles to help describe, categorize, and predict the behavior of these systems. The theoretical machinery already available, or ones to be discovered to help solve biological problems, might play an important role in these processes. Here, we demonstrate the application of theoretical tools by discussing some biological problems that we have approached mathematically: fluctuations in gene expression and cell proliferation in the context of loss of contact inhibition. We discuss the methods that have been employed to provide the reader with a biologically motivated phenomenological perspective of the use of theoretical methods. Finally, we end this review with a discussion of new research perspectives motivated by our results.
Subject(s)
Humans , Gene Expression Regulation, Neoplastic , Stochastic Processes , Models, Biological , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathologyABSTRACT
To study proliferation of the retinal pigment epithelium (RPE) after experimental retinal detachment, an antibody that recognizes the specific proliferating cell nuclear antigen (PCNA) in proliferating cells was used. Retinal detachment was produced in cats by subretinal injection of 0 25% solution of Healon through a micropipette. At different intervals the animals were sacrificed and eye globes were fixed in 10% at malin and embeded in paraffin. Histologic sections were processed for immunohistochemisty using an antibody to detect the PCNA protein. Labeled RPE cells were identified, and the proliferative response was quantified. In the retina detached at 0 5, 1, 2, 3, 4, 5, 6, 7, 10, 14, 20, 30, and 60 days, the number of PCNA labled cells was 0 055, 0 444, 0 861, 1 972, 3 139, 5 833, 6 028, 4 917, 3 333, 2 195, 1 083, 0 195, and 0 056 cells per millimeter of retina, respectively. In non detached retina of the same eye, approximately from 0 to 0 639 cells per millimeter of retina were labeled. The difference of PCNA labeled cells between detached and non detached retina of the same eye was significant. These results indicate that RPE cells are induced to proliferate when they lose contact with neural retina.
ABSTRACT
Objective To examine the expression of proliferating cell nuclear antigen (PCNA) of retinal pigment epithelial (RPE) cells, thus assessing the role of mechanism of contact inhibition playing in the process of experimental retinal detachment and reattachemnt. Methods Retinal detachment was produced in 72 cats by subretinal injection of 0.25% solution of healon through a micropipette three weeks after extracapsular lens extraction and vitrectomy. Some of the detached retinae were reattached 24 hours later. At different time, the cats were killed and eye globes were fixed and embeded in paraffin. Histologic sections were processed for immunohistochemistry examination using an antibody to detect PCNA protein. Labeled RPE cells were identified, and the proliferation was quantified in detached and un detached retinae of detachment group, and also in reattached retinae of reattachment group. The comparsion of PCNA labeled RPE cells in different groups were analyzed by ANOVA. Results In detached regions of detachment group, PCNA expression of RPE cells occured within 24 hours, and reached a maximum after 5 6 days, then gradually declined to barely detectable levels after 20 days. Similar tendency was found in reattached retinae, but the number of PCNA labeled RPE cells was obviously small. Fewer PCNA labeled RPE cells were found in regions of un detached retinae in detachment group. The difference of these three groups was significant. Conclusion Proliferation of RPE cells is induced when they lose contact with neural retina, but inhibited after neural retina reattached to RPE cells. It suggests that the mechanism of contact inhibition plays a role in the proliferative process after retinal detachment and reattachment.