The long-term goal of this project is to understand rod outer segment (ROS) photoreceptor mechanisms in retinal degeneration so that medical treatment strategies can be developed to prevent or retard the process. From previous studies we know that ROS membranes function abnormally under pathological conditions associated with light-exposure or oxidative-stress of the retina. Critical to this is the role of ROS disk and plasma membrane lipids. We hypothesize that alterations in the lipid composition and structure under pathological conditions influence ROS photoreceptor membrane performance. Therefore, the goal of this investigation is to examine the conformational, compositional and structural characteristics of the normal and dysfunctional ROS membranes, and explore the role lipids play in photoreceptor function. We will pursue this goal by measuring structural alterations in lipids and proteins of the ROS disk and plasma membranes subjected to oxidative-stress produced physiochemically and by light. State-of-the- art spectroscopic non-invasive Fourier transform infrared techniques will be used to achieve these goals. The spectroscopic findings will be correlated to the physiological response of the retina by measuring ERG signals of the control and light-exposed rats thus providing a direct means of testing our single hypothesis. Our primary source of ROS disk and plasma membranes are bovine and rat retinas. We plan to answer three key questions: I. What is the lipid composition of the ROS (disk and plasma) membranes in retinas subjected to pathological conditions? II. What are the structural changes associated with the ROS (disk and plasma) membranes in dysfunctional retinas? III. How is ROS membrane lipid and rhodopsin structure affected by changes in the content and/or composition of lipid moieties, and how do they correlate to the physiological response of the ROS photoreceptor? The lipid moieties are: acyl chain saturation, cholesterol, trans retinol, docosahexanoic acid and compounds reflecting oxidative-stress produced physiochemically and by light-exposure. Such studies will permit us to develop an in-depth appreciation of the relatively subtle changes in membrane properties which contribute to ROS membrane structure-function relationships. In addition, our studies of ROS membrane perturbations will help determine the role membranes in diseases associated with ROS derangement. The results of this study will strengthen the foundation of knowledge necessary to assure future development of medical therapy for age-related retinal diseases.
| Boesze-Battaglia, K; Lamba, O P; Napoli Jr, A A et al. (1998) Fusion between retinal rod outer segment membranes and model membranes: a role for photoreceptor peripherin/rds. Biochemistry 37:9477-87 |
| Boesze-Battaglia, K; Kong, F; Lamba, O P et al. (1997) Purification and light-dependent phosphorylation of a candidate fusion protein, the photoreceptor cell peripherin/rds. Biochemistry 36:6835-46 |
