Retinoid kinetics in eye tissues of VPP transgenic mice and their normal littermates

PURPOSE. VPP mice, which possess a mutant transgene for opsin (V20G, P23H, P27L), exhibit a progressive rod degeneration that resembles one form of hu man autosomal dominant retinitis pigmentosa. In the present study the assoc iation of the development of VPP rod degeneration with abnormal operation o f the retinoid visual cycle was examined. METHODS. Dark-adapted VPP mice and normal littermates were anesthetized and the pupils dilated. One eye of each animal was illuminated for 2 minutes; the other eye was shielded from the Light and served as a control. Each ani mal was then dark adapted for a defined period (0-300 minutes) and killed. Retinoids contained in the retina, retinal pigment epithelium (RPE), and ex tracellular medium were recovered by means of formaldehyde-, isopropanol- a nd ethanol-based extractions and analyzed by high-performance Liquid chroma tography. RESULTS. Total amounts of retinoid recovered from unilluminated eyes of 2-m onth-old normal and VPP mice were 425 +/- 90 picomoles per eye and 115 +/- 33 picomoles per eye, respectively (mean +/- SD). Relative distributions of retinoids within normal and VPP eyes were similar. In normal and VPP anima ls, illumination for 2 minutes produced a similar immediate reduction in th e molar percent of total retinoid represented by Il-cis retinal in the reti na (average reduction of 34% and 28% in normal and VPP animals, respectivel y) and a similar transient increase of all-trans retinal in the retina. In both groups the decline of all-trans retinal was accompanied by an increase in total retinyl ester. In normal and VPP animals, a period of approximate ly 40 minutes or more preceded initiation of the recovery of Il-cis retinal in the retina, and the time course of this recovery was generally similar to that for the decline of retinyl ester. The overall dark-adaptation perio d required for half-completion of Il-cis retinal recovery was approximately 150 minutes. In neither group did illumination produce a substantial peak of all-trans retinol in the retina. CONCLUSIONS. The evident approximately fourfold reduction of total retinoid in the eyes of 2-month-old VPP mice is consistent with histologic and elec troretinographic abnormalities determined in previous studies. Despite this marked abnormality in retinoid content, retinoid cycling in the VPP is rem arkably similar to that in normal littermates. The data place constraints o n the functional consequences of any abnormality in retinoid processing tha t may be present at this stage of the VPP rod degeneration.