The objective of these studies is to understand the mechanism and implications of tocopherol, cholesterol, and phospholipid delivery to the retina as factors contributing to the pathogenesis of various retinal degenerations, such as retinitis pigmentosa, retrolental fibroplasia, vitamin E deficiency. Accordingly the specific aims are 1) to determine the nature of the retinal pigment epithelial (RPE) cell lipoprotein receptor activity 2) to assess LP uptake by RPE using LPs from a variety of physiological and nutritional circumstances 3) to determine the correlates (apoprotein and lipids) of preferred tocopherol transport by lipoproteins 4) to measure the cholesterol synthesis in RPE as affected by LP uptake. The hypothesis to be tested is that tocopherol and EFA transport across the blood brain barrier (e.g., the RPE) depends on adequate receptor activity and appropriately """"""""charged"""""""" LPs. To this end we will study cultured bovine and human RPE to measure normal receptor binding and uptake of normal LPs (chylo remnants, VLDL, LDL, HDL) and debris (photoreceptor outersegments, damaged LDL) on both apical and basilar surfaces of RPE. This will be followed by studies of LPs from infants (cord blood) and adults (normo and hyperlipemic, patients with RP) or animals fed different dietary fats (saturated vs PUFA), cholesterol, and with or without vitamin E deficiency. In this way we will generate a wide variety of LPs to examine the physiology of LP uptake and lipid delivery to the retina on the assumption that the results will enhance our understanding RPE transport of lipids and associated retinal lipid metabolism.
| Pronczuk, A; Kipervarg, Y; Hayes, K C (1992) Vegetarians have higher plasma alpha-tocopherol relative to cholesterol than do nonvegetarians. J Am Coll Nutr 11:50-5 |
| Hayes, K C; Lindsey, S; Stephan, Z F et al. (1989) Retinal pigment epithelium possesses both LDL and scavenger receptor activity. Invest Ophthalmol Vis Sci 30:225-32 |
