Effect of 670 Nm Photobiomodulation on Angiogenic and Inflammatory Signaling Pathways in an in Vitro Model of Diabetic Retinopathy
Date of Award
Master of Science
Elizabeth S Liedhegner
Elizabeth S Liedhegner, Janis T Eells, Dean T Nardelli
Angiogenesis, Diabetic retinopathy, Inflammation, Light therapy, Muller cells, Photobiomodulation
Approximately 1 in 10 Americans suffers from diabetes mellitus, and the frequency escalates to 1 in 4 for individuals over 65 years of age (Centers for Disease Control and Prevention, 2020). These statistics are jarring considering the absence of a cure forces patients to endure lifelong physician supervised disease management or increase their risk of developing vascular complications. Alas, even patients able to obtain world-class research informed treatments and lifestyle advice may still be afflicted with macrovascular and microvascular dysfunction as the disease progresses. Insulin deficiency and resistance leads to metabolic dysregulation and fosters an environment saturated with glucose due to insufficient hormone-mediated translocation into adipose and muscle tissue (Wilcox, 2005). Hyperglycemia coincides with dyslipidemia, mitochondrial dysfunction, and aberrant cellular signaling with devastating consequences including the most common microvascular consequence, diabetic retinopathy (DR). Importantly, exposure to high glucose directly is not the sole source of cellular distress in DR, but, rather, downstream signaling initiated by excessive blood sugar induces chronic inflammation and expression of angiogenic factors that contribute to pathogenic growth of widespread yet poorly constructed vessels that often advance into ocular pathologies and severely threaten a patient’s vision (Busik, Mohr, & Grant, 2008). Far red/near-infrared (R/NIR) photobiomodulation (PBM) is a non-invasive therapy that has been shown to ameliorate inflammatory mediators and stabilize mitochondrial activity in several animal and cell culture disease models, including DR. Accordingly, we hypothesized that light therapy at 670 nm will enhance expression of anti-angiogenic proteins and attenuate high glucose-induced mediators of inflammation in a rat retinal Müller cell model of diabetic retinopathy. This hypothesis was tested with the following the following focuses. Specific aim 1: Identify expression of anti-angiogenic proteins under high glucose conditions in a cultured Müller cell model of diabetic retinopathy and when treated with 670 nm PBMT. Specific aim 2: Identify inflammatory and angiogeneic cytokines expressed under high glucose conditions in a cultured Müller cell model of diabetic retinopathy and determine the effect of 670 nm PBMT. Research objective: This study will evaluate whether inflammatory and angiogenic mediators affected by high glucose can be attenuated with PBM to further enhance understanding of the technology and its potential to treat DR patients. Results: We found that high glucose mildly, if at all, affects TSP-1 expression within and secreted by Müller cells (MCs). In addition, 670 nm PBM tends to increase expression of TSP-1 within and secreted by MCs. These findings suggest trends but lack significance (p<0.05). We were unable to visualize TGF-β due to serum interference. Similarly, unanticipated assay limitations prevented quantification of IL-1β, IL-6, IL-10, and TNF-α in Müller cell conditioned media as sample concentration measurements failed to fall within the standard curves.
Lofald, Annamarie Grace, "Effect of 670 Nm Photobiomodulation on Angiogenic and Inflammatory Signaling Pathways in an in Vitro Model of Diabetic Retinopathy" (2022). Theses and Dissertations. 3036.
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