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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08EY016357-05
Application #
8541856
Study Section
Special Emphasis Panel (ZEY1-VSN (03))
Program Officer
Agarwal, Neeraj
Project Start
2009-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$179,250
Indirect Cost
$13,150
Name
University of Maryland Baltimore
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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