An Exploratory Microdialysis Study to Assess the Ocular Pharmacokinetics of Ciprofloxacin Eye Drops in Rabbits.

PURPOSE: Despite the high frequency of use, data regarding the ocular in vivo pharmacokinetics (PK) of topically applied antibiotics are sparse. This study seeks to investigate the PK of the widely used fluoroquinolone ciprofloxacin by means of in vivo microdialysis. METHODS: Twelve New Zealand white rabbits were included in the experiments. Under general anesthesia, microdialysis probes were implanted in the anterior chamber and the posterior segment of the same eye. After a period of 90 min after implantation, one drop of ciprofloxacin was administered onto the ocular surface. Microdialysis samples of the anterior chamber and the vitreous were collected every 30 min for 6 h. Relative recovery was assessed by retrodialysis to calculate absolute concentration values. Samples were analyzed using HPLC. RESULTS: In the anterior chamber, the maximum total drug concentration (Cmax) amounted to 0.373 ± 0.281 µg/mL and was reached (Tmax) after 116 ± 36 min. Calculated area under the concentration-time curve AUC(0-n) for ciprofloxacin in the anterior chamber was 78.8 ± 47.1 µg min/mL. For the vitreous, Cmax was 0.02 ± 0.03 µg/mL and maximum drug concentration was reached 107 ± 60 min after topical administration. AUC(0-n) for ciprofloxacin in the vitreous was 0.269 ± 0.370 µg min/mL. CONCLUSION: Microdialysis is a suitable method to assess in vivo pharmacokinetic profiles in the anterior chamber and in the vitreous. In the anterior chamber, maximum drug concentration was reached ∼2 h after single drug administration. Although the drug concentration in the vitreous was considerably lower, time course of drug concentration was comparable.

Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse.

Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm) and Mus m. domesticus (Mmd), it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2) genomic locus on Chromosome X (Chr X) by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s) responsible for variation in the global recombination rate between closely related mouse subspecies.

Measurement of retinal blood flow in the rat by combining Doppler Fourier-domain optical coherence tomography with fundus imaging.

A wide variety of ocular diseases are associated with abnormalities in ocular circulation. As such, there is considerable interest in techniques for quantifying retinal blood flow, among which Doppler optical coherence tomography (OCT) may be the most promising. We present an approach to measure retinal blood flow in the rat using a new optical system that combines the measurement of blood flow velocities via Doppler Fourier-domain optical coherence tomography and the measurement of vessel diameters using a fundus camera-based technique. Relying on fundus images for extraction of retinal vessel diameters instead of OCT images improves the reliability of the technique. The system was operated with an 841-nm superluminescent diode and a charge-coupled device camera that could be operated at a line rate of 20 kHz. We show that the system is capable of quantifying the response of 100% oxygen breathing on the retinal blood flow. In six rats, we observed a decrease in retinal vessel diameters of 13.2% and a decrease in retinal blood velocity of 42.6%, leading to a decrease in retinal blood flow of 56.7%. Furthermore, in four rats, the response of retinal blood flow during stimulation with diffuse flicker light was assessed. Retinal vessel diameter and blood velocity increased by 3.4% and 28.1%, respectively, leading to a relative increase in blood flow of 36.2%. The presented technique shows much promise to quantify early changes in retinal blood flow during provocation with various stimuli in rodent models of ocular diseases in rats.