PURPOSE: Rod, cone, cone-rod, and macular dystrophies eventually bring about the 
death of cone photoreceptor cells. The present study explores means of 
inhibiting apoptosis in addition to inducing a specific apoptotic pathway within 
a photoreceptor-derived cell line.
METHODS: Retinal cell culture of murine 661W photoreceptor-derived cells was 
used to assess the effect of both a synthetic peptide inhibitor of caspases 
(benzyloxycarbonyl-Val-Ala-DL-Asp-[Ome] fluoromethylketone [Z-VAD.FMK]) and a 
natural inhibitor, baculoviral p35. In addition, the effect of transfection of 
Fas-associated death domain (FADD), a cellular protein implicated in 
receptor-induced apoptosis, was assessed. Assays were performed by transient 
transfection of cell cultures, and results were recorded by cell counting, 
Western blot, and spectrophotometry.
RESULTS: Western blot analysis and chromogenic caspase substrate cleavage 
analysis confirmed the activation of caspases within 661W cells. At a 
concentration of 80 micro M, Z-VAD.FMK, 72.36% +/- 0.93% of 661W cells survived 
cytotoxic insult compared with 6.99% +/- 1.35% of control cells. Transient 
transfection of 1200 ng baculoviral p35 conferred a protection of 75.30% +/- 
4.23%, compared with 19.61% +/-1.84% of control cells, and it was additionally 
observed that as little as 50 ng transfection of FADD was capable of inducing 
the death of 53.21% +/- 1.33% of cells in 661W cultures.
CONCLUSIONS: Apoptotic cell death in 661W cells is caspase dependent and may be 
inhibited with both a synthetic and natural inhibitor of caspase function. 
Furthermore, 661W cells are highly sensitive to the FADD protein, which may 
suggest a number of novel therapeutic approaches to halt photoreceptor cell 
apoptosis.