This proposal describes a 5 year program for the development of an academic research career in Ophthalmology. I have completed a postdoctoral research fellowship, followed by residency and fellowship training in Ophthalmology/ Neuroophthalmology. Now I will focus upon expanding my scientific and research skills through a unique integration of interdepartmental resources and mentorship. Career development activities will promote the command of research methodology, as well as vascular biology and microbiology of the eye, as applied to mechanisms of atherosclerotic and ischemic eye disease. Steven L Bernstein, MD, PhD and Charlene Hafer-Madco, MD will mentor my scientific development. Dr. Bernstein is a renowned leader in the research of nonarteritic anterior ischemic optic neuropathy (NAION), and has developed a unique rodent photoembolic stroke model (rAION). Dr. Hafer-Macko's primary research interest in prothrombotic disease mechanisms relate to the focus of fhis proposal. Both mentors have trained numerous postdoctoral fellows, graduate students and residents. To enhance the training, the program will enlist the expertise of an advisory committee of highly regarded medical scientists. Research will focus on investigating the role of Lipoprotein(a) (Lp(a)) and Low-density lipoprotein (LDL), two closely related, well-defined risk factors of premature atherosclerosis, in ischemic eye disease. I will explore the correlation of Lp(a) deposition with atherosclerosis in the eye and the effect of increased Lp(a) and LDL serum levels on susceptibility to ischemic optic neuropathy. If successful, proving a correlation between elevated lipoprotein serum levels, ischemic optic neuropathy and atherosclerosis may lead to earlier diagnosis and treatment of atherosclerosis to prevent severe complications of this disease.
Specific aims i nclude: 1) Localizing and quantifying Lp(a) deposition in the eye, 2) Establishing an in vivo model for the analysis of the effect of increased serum Lp(a) and LDL in ischemic optic neuropathy. This will be the first detailed investigation into these specific mechanisms of atherosclerotic eye disease. The University of Maryland provides an ideal setting for the proposed career development award (CDA) by providing strong institutional support for the development of junior faculty members into independent scientists. This CDA will allow the University of Maryland to provide me with the necessary protected time, resources, and training to successfully transition from a clinical appointment into an academic career in ophthalmology research.

Public Health Relevance

The proposed research is based on the hypothesis that in the eye, similar to the heart and brain, Lp(a) and LDL promote atherosclerotic plaque formation and inflammation, leading to intravascular thrombosis and ischemic events, such as ischemic optic neuropathy. These lipoproteins are well established as risk factors for atherosclerotic heart disease and stroke. Therefore, establishing a correlation between Lp(a), LDL and ocular ischemia may lead to new prevention strategies for atherosclerosis and associated life-threatening diseases as well as provide insight into the etiology of ophthalmic disease.

National Institute of Health (NIH)
National Eye Institute (NEI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZEY1-VSN (03))
Program Officer
Shen, Grace L
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University of Maryland Baltimore
Schools of Medicine
United States
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Malouf, Marc A; Levin, Moran; Mathews, Michaela K (2016) Leber's Hereditary Optic Neuropathy--Not Just a Young Men's Disease. J Am Geriatr Soc 64:237-9
Mathews, Michaela K; Guo, Yan; Langenberg, Patricia et al. (2015) Ciliary neurotrophic factor (CNTF)-mediated ganglion cell survival in a rodent model of non-arteritic anterior ischaemic optic neuropathy (NAION). Br J Ophthalmol 99:133-7
Bhatt, Nirali P; Morales, Robert E; Mathews, Michaela K (2013) MRI findings in Post-operative Bilateral Posterior Ischemic Optic Neuropathy. Open J Ophthalmol 3:51-53
Sayegh, Rony R; Madsen, Kimberly A; Adler, Jason D et al. (2012) Response to TASER electronic control devices and eye injuries. Doc Ophthalmol 124:161-2
Sayegh, Rony R; Madsen, Kimberly A; Adler, Jason D et al. (2011) Diffuse retinal injury from a non-penetrating TASER dart. Doc Ophthalmol 123:135-9