Obstructive sleep apnea (OSA) and Type 2 diabetes mellitus (T2DM) are epidemic, comorbid conditions which affect millions of patients worldwide. While the complex relationship between OSA and T2DM is still poorly understood, the pathophysiological changes that underlie OSA and T2DM-related complications indicate overlapping, synergistic mechanisms. Importantly, severe ocular complications have been reported with both conditions. T2DM has been identified as a leading cause of adult blindness, including chronic, often painful, corneal complications resulting from diabetic corneal neuropathy. Research investigating the effects of hyperglycemia in T2DM on corneal nerves is limited, as current studies have failed to address the interactive effects of co-existent condition such as OSA. Recently, a potential link between OSA, T2DM and diabetic peripheral neuropathy has been identified. The goal of this R21 project is to identify and characterize novel relationships between OSA, T2DM and pathological corneal nerve changes that may help us to mitigate the potentially additive effects of OSA on corneal and ocular surface disease. In this proposal, we will test two novel hypotheses: (1) that corneal nerve morphology is altered in patients with OSA resulting in pathological corneal and ocular surface changes; and (2) that the interaction between OSA and T2DM exacerbates the deleterious effects of hyperglycemia on the corneal subbasal nerve plexus (SBNP), leading to increased ocular surface damage in patients with comorbid disease. We will test these hypotheses in Aim 1 using in vivo confocal microscopy to investigate potential corneal nerve and epithelial cell changes in patients with OSA, T2DM and comorbid disease compared to healthy controls. In Aim 2, we will examine potential systemic variables that are associated with alterations in the SBNP and assess the subsequent effects of changes in the SBNP on the ocular surface. This exploratory proposal utilizes a comprehensive multidisciplinary team approach to investigate a novel contributory role for OSA in diabetic corneal neuropathy. Unlike Type 1 disease, available evidence suggests that glycemic control alone is not sufficient to halt the neuropathic complications of T2DM. This study will establish, for the first time, whether corneal nerve morphology is altered in OSA and provide insight into the potential inflammatory and immunological mechanisms associated with OSA that contribute to the pathophysiology of corneal nerve damage in diabetic disease. The inclusion of co-morbid disease associated with T2DM represents an innovative clinical approach towards understanding the biology of diabetic-induced nerve loss.
NIH ExPorter
NIH ExPorter