A cell culture system related to extended in vitro culture of mature retinal cells and methods for preparing the cell culture system are provided. Also provided is a retinal cell culture stress model related to extended in vitro culture of mature retinal cells in the presence of a stressor and methods for using the cell culture stress model. The invention provides a cell culture system comprising a long-term culture of mature retinal cells, without requiring addition of other types of non-retinal cells such as purified glia, or cells isolated from ciliary bodies within the eye, and the addition of a stressor such as light, A2E, cigarette smoke condensate, glutamate, or hydrostatic pressure. Methods for identifying bioactive agents that alter viability, neurodegeneration, or survival of retinal cells using the retinal cell culture stress system are also provided.