Protein binding ocular tissues

Aminoglycosides are not well absorbed from the gastrointestinal tract but are well absorbed after intramuscular or subcutaneous injection. Effective concentrations are achieved in synovial, pleural, peritoneal, and pericardial fluids. Intrauterine and intramammary administration is also effective, but significant tissue residues result. Aminoglycosides do not bind significantly to plasma proteins, and as they are large polar molecules, they are poorly lipid-soluble and do not readily enter cells or penetrate cellular barriers. This means that therapeutic concentrations are not easily achieved in cerebrospinal or ocular fluids. Tlieir volumes of distribution are small, and the half-lives in plasma are relatively short (1-2 h). Elimination is entirely via the kidney. 

Recently, a new mouse model was developed that allows us to examine photoresponses in an entirely opsin-free mouse model. Opsins require their chromophore, 11-cis-retinal, for function, and therefore, one obvious approach to create an opsin-free model would be to deprive mice of dietary vitamin A, rendering aU opsins nonfunctional, including rod and cone opsins as well as known and yet to be discovered novel opsins. This approach is not feasible in normal mice, because vitamin A is required during development, and adult mice have stored sufficient vitamin A in their Hver to last for the lifetime of the animals, even if they were put on a vitamin-A-free diet. The creation of the plasma retinol-binding protein mutant rbp) enables us to deplete ocular retinal in mice. The Rbp protein transports retinal from storage in the Hver to peripheral tissues. With the Rbp mutation, peripheral tissues such as the eye can be vitamin A depleted in 6 to 8 months. Therefore, we used the vitamin-A-depleted rhp mouse as an opsin-free model for circadian photoreception. 

---