Results from large clinical trials demonstrate a strong association between lipid abnormalities and progression of the most common microvascular complication, diabetic retinopathy (DR). We found that activation of a master regulator of cholesterol metabolism, the nuclear hormone receptors liver X receptors (LXRα/LXRβ), prevents DR in rodent models. In this application, we seek to understand the mechanisms responsible for the beneficial effects of LXR agonists on retina and on bone marrow (BM) to preserve the function of reparative cells while reducing inflammatory cell.
Any man or woman between the ages of 21- 98 years of age will be eligible to participate. To participate in the study as a study subject we will require: a) the subject must either carry the diagnosis of diabetes or be a healthy aged control and b) the patient be willing and have the ability to cooperate with the protocol.
Exclusion criteria: We will apply the following exclusion criteria: a) evidence of ongoing acute or chronic infection (HIV, Hepatitis B or C, tuberculosis); b) ongoing malignancy; c) cerebral vascular accident or cerebral vascular procedure; d) current pregnancy; e) history of organ transplantation; f) presence of a graft (to avoid any effect of the graft on inflammatory parameters; g) uremic symptoms, an estimated glomerular filtration rate of less than 20 cc/min (by Modification of Diet in Renal Disease equation), or an albumin of less than 3.6 (to avoid malnutrition as a confounding variable); h) be unwilling to abstain from drinking alcohol and i) patients with anemia. Subjects with AMD, glaucoma, uveitis, known hereditary degenerations or other significant ocular complications other than diabetic retinopathy will be excluded.
Patients who have retinal abnormalities other than diabetic retinopathy will be excluded. Patients who have systemic conditions that influence hematopoietic stem cell function such as cardiovascular disease, malignant disease, diabetes, hematologic disorder, or estimated glomerular filtration rate less than 60 mL/min or who have undergone treatment with erythropoietin will be excluded. We will record all medications including antihypertensive drug treatment, treatment with statins, Angiotensin-Converting Enzyme (ACE) Inhibitors, Angiotensin Receptor Blockers (ARB) or other pharmacological agents that may influence CD34+ cell function. Baseline characteristics will be recorded, including age, lipid parameters, body mass index (BMI), blood pressure, smoking history, antioxidant intake and use of nutritional supplements.
Cohort
Other
blood draw
Biological/VaccineBlood sample will be obtained and CD34+ cells will be isolated for functional testing.
6
Treatment groupsSee each treatment group below.
Assessing CD34+ cells function
We are isolating CD34+ cells from peripheral blood and then examining the cell membrane characteristics of CD34+ cells and their in vitro function.
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