Abstract
Purpose: :
To determine whether Minocycline, a compound known to be protective against light damage in animal models, would protect photoreceptor cells in primary bovine retinal cell culture.
Methods: :
Optimal dose of light exposure was established to induce preferential cell–death of photoreceptors in primary bovine retinal cell cultures. Minocycline and other members within the family of naphacene antibiotics were tested to see if they would inhibit light induced cell death. A primary screen using Sytox Green (Molecular Probes, Eugene, OR) was used to identify putative cytoprotective activity. Active compounds were then examined using immunocytochemistry for differential protection of photoreceptor cells. Cytoprotective compounds for photoreceptors were reassayed at various concentrations to estimate EC50.
Results: :
Some members in the tetracycline family of compounds including minocycline have been found to be cytoprotective against light damage with an EC50 <10 µM. In contrast, structurally related demeclocycline was toxic in the presence of light, showing that minor structural changes within this class of molecules can affect its light–protective activity.
Conclusions: :
Minocycline’s protective action against light damage in the cell–based assays and in animal models suggest that the in vitro assay based on protection of photoreceptors from light damage in bovine primary retinal cell culture is a suitable model for evaluating compounds for retinal protection. The finding of toxic compounds within this family also suggests the utility of the retinal cell–based assay to screen out compounds that are toxic to primary retinal cells.
Keywords: photoreceptors • neuroprotection • cell survival