Secondary cone degeneration in the transgenic rats carrying the S334ter rhodopsin mutation (S334ter-3 rats) starts at the peak of rod degeneration (PD12) and progresses with age. An early sign of cone degeneration is the loss of cone outer segments (COS) distributed in many small patches throughout the retina. Cone cell death occurs about 2 months later. When treated with CNTF (ciliary neurotrophic factor), impaired cones regenerate COS. Sustained delivery of CNTF prevents cones from degeneration and helps to maintain COS and function. These results indicate that cone degeneration is reversible at early stages and support a therapeutic strategy of sustained delivery of CNTF to prevent cone degeneration.