Providing Toxicological Expertise on Cataract Development
The appearance of lens opacities during the toxicological phase of systemic drug development in either long-term rat, dog, and preclinical or clinical human studies can quickly result in the death of a promising drug or drug class project. Our extensive experience in in vitro lens culture and expertise in lens biochemistry can quickly identify specific adverse biochemical mechanism(s) of action of the candidate drug so that project development can be saved. Customers include Merck and Company, Johnson & Johnson Pharmaceutical Research and Development, and Vertex Pharmaceuticals.
The crystalline lens is a transparent avascular structure composed primarily of structural proteins and water that is surrounded by a collagen capsule. Anteriorly the lens contains a monolayer of epithelial cells which divide, elongate and differentiate to form the regularly arranged lens fibers that are concentrically laid down throughout life. Without a direct blood supply, the lens receives all essential nutrients from the aqueous humor and most of the metabolic, synthetic and transport processes of the lens occur in the epithelial cells. As a result, the lens exists in an environment that is analogous to a single-cell type of tissue culture system. Because the chemical properties of the encapsulated lens allow it to behave both electrically and chemically like a single cell, the lens can serve as a sensitive indicator of chemical toxicity. In vitro culture studies have been established as a reproducible method for not only elucidating the complex biochemical pathways of the lens but also identifying the metabolic changes associated with cataract formation.
Using the optimum methodology established by the Kinoshita Laboratory at the Howe Laboratory at Harvard and later the National Eye Institute, we are experienced at successfully culturing and maintaining lens clarity as well as lens biochemical parameters of mouse, rat, dog, and human lenses for culture periods of up to 72 hours. Lens clarity can be maintained for longer periods; however, lens metabolic parameters are quickly reduced at longer culture periods. More importantly, while changes in lens metabolism can result in lens opacification, maintenance of lens clarity does not guarantee that lens metabolism has not been altered or reduced.
To see a detailed example on how this technique can quickly elucidate the adverse effects of an experimental drug click here.