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Amirfarbod Yazdanyar, Xian-Cheng Jiang, Douglas Lazzaro, William Brunken; The Role of Phospholipid Transfer Protein (PLTP) in Lipoprotein Metabolism in the Retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1374.
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Age-related macular degeneration (AMD) is characterized by the loss or dysfunction of retinal pigment epithelium (RPE) and is the most common cause of vision loss among the elderly. The most prominent pathological change in AMD is the accumulation of lipids in the form of drusen around Bruch’s membrane with consequent impairment of RPE function. Unlike atherosclerosis, AMD development is not directly related to plasma cholesterol levels. However, AMD may result from a local dysregulation of lipid homeostasis. RPE cells express various genes that regulate lipoprotein metabolism including Phospholipid transfer protein (PLTP). PLTP has long been studied for its critical role in apoB-containing particles (BLp) as well as high density lipoprotein (HDL) metabolism. While the function of PLTP in lipid homeostasis in the retina, and specifically in RPE cells, remains elusive, we hypothesize that PLTP dysregulation may be involved in AMD pathogenesis.
To test this hypothesis and to elucidate the role of PLTP in retinal lipoprotein metabolism, we took advantage of our PLTP transgenic (tg) mice which were fed ad libido with a high fat/carbohydrate diet to induce obesity/diabetes. Then we performed dilated fundus exam (DFE), fluorescein angiography (FA) and oil Red O staining.
After 4 months, we performed DFE and found that our PLTP tg model developed numerous significant sub-retinal drusenoid lesions while our wild type (WT) control group had fewer lesions. To further investigate the nature of the retinal lesions, we stained the fresh frozen sections of the eye balls from both groups with oil Red O staining. We found that in addition to the expected accumulation of lipid in the vascular wall, the PLTP tg mouse accumulated more lipid in the retina including in the RPE and Bruch’s membrane. Moreover, FA revealed that PLTP tg animals have severe signs of ischemia including capillary drop out, vascular beading, and leakage of fluorescein dye when compared to the control mice.
Based on our observations, we believe that PLTP may play a significant role in lipoprotein metabolism in the retina and dysregulation of this gene may lead to subretinal lipid accumulation. Further study of PLTP function in the retina, and RPE, is timely and insights gained may provide rationale for novel therapeutic treatments of AMD.
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