Background Age-related cataract affects 22% of individuals over the age of 75 years, and data suggest that delaying the progression rate by 10 years would decrease cataract surgery by 50%. When rodent lenses are incubated in culture medium, they lose their transparency after 24-48 hours due to protein aggregation, which changes the index of refraction resulting in light scattering and opacity. We hypothesized that finding ways to prevent or delay this process through manipulation of the culture medium would provide important clues toward cataract prevention and present a solid foundation for a drug testing model on specific mutated mice lenses for cataract treatment. Methods 13 culture conditions, each comprising 4-6 adult C57BL6 mice lenses, were tested. Variations in glucose, pyruvate, fructose, antioxidant, osmolality (sorbitol), and crowding agent (polyethylene glycol) were used. The extent of opacification, the type of opacity (nuclear vs cortical), and the lens diameter were determined as a function of incubation time. Results Results show that compared to the baseline conditions (Medium TC199), basic nutrition materials that lenses need for survival and antioxidants that prevent oxidative stress in lenses show no improvement in preventing lens opacification. Next, we mimicked the lens environment in the eye and tested hyperosmolarity. PEG 1000 stood out among the rest by successfully preventing cataract formation in all of its lenses. We also noticed the lens size difference between the PEG 1000 condition and the rest. PEG 1000 successfully prevents the lens from swelling and keeps lens volume low. Thus, from our results, we tested another set of biopolymers which could prevent massive intake of medium to the lens that we saw in previous conditions. We saw that Lymphoprep successfully kept lenses clear until day 4 (96 hours), which was a major improvement compared to the rest of the conditions that we tested. Conclusion This project is novel in its approach as the first to develop a system of drug testing lens model for cataract by keeping mice lenses clear and transparent for 7-14 days. While we are still in the process of reaching 7-14 days of clarity in lenses, we have already tested some strong potential conditions that improved lens transparency in vitro incubations, such as PEG 1000 and Lymphoprep. We plan to further test possible conditions for optimizing lens culture medium for in vitro lens transparency, specifically focusing on mimicking the lens environment in the eye to maintain lens homeostasis.