Research Interest

Research Description And Accomplisment

Research Activities

Overview:Dr. Le is a cell and molecular biologist and a mouse geneticist. His research is focused on the retinal cell-specific genetic switch, mechanisms and therapeutic strategies for diabetic retinopathy (DR), age-related macular degeneration (DR), and retinal neuron dysfunction and degeneration. His work is in the targeted research areas of NIH/NEI and major vision research funding agencies.
Conditional gene targeting:Dr. Le is a pioneer in establishing conditional gene expression systems and has used them to delineate the cellular mechanisms for these diseases/biological processes in the retinal biology field. He has generated a number of Cre-drive lines for conditional gene targeting in a variety of retinal cells. These systems have provided a firm foundation for research in cellular mechanisms of biological processes and diseases in the retina and have contributed significantly to the understanding of age-related macular degeneration, juvenile macular dystrophy, diabetic retinopathy, protein trafficking, inherent retinal degeneration, photoreceptor survival, and visual signaling.

Mechanisms of blood-retina barrier breakdown in DR:DR is the No. 1 cause of blindness in working aged Americans. Dr. Le has brought his expertise in conditional gene expression to the field and has been delineating the cellular mechanisms of this disease. The significance of his approach was discussed by a cover-story-editorial in a journal for practicing ophthalmologists, Retina Today (I: 31, 2007). For the first time in an in vivo setting, his group unequivocally demonstrated the pathological role of Müller glia-derived vascular endothelial growth factor (VEGF) in retinal inflammation, neovascularization, vascular leakage, and vascular lesions, common pathogenic changes in DR. His work was published in high impact Journals, such as Diabetes, Diabetologia, and J. Pathology. Recently Dr. Le’s lab establishes a new niche in the by tackling the role of retinal pigment epithelium (RPE) barrier in DR. His lab has resolved a 30-year technical problem by establishing an imaging assayforde novo leakage of macromolecules through the RPE barrier, which demonstrates that substantial leakage is coming from the RPE barrier. This finding challenges the current dogma of vascular leakage and is likely to change our view on the mechanism of diabetic macular edema (DME). The combination of using this imaging assay and conditional gene targeting has revitalized the interest in diabetes-induced RPE barrier breakdown, which is likely to set a new milestone in the understanding, diagnosis, and treatment of DME, a major vision loss in diabetic patients.

Mechanisms of retinal neuron alteration and degeneration in DR: Dr. Le has been working on retinal neuron survival under pathological conditions since he joined vision research field. He is a leader in using conditional gene expression approach to address neuron-specific mechanisms. His current work on treating DR-induced neuron degeneration through Müller cell proliferation, is likely to set a new paradigm in neuro-protection. As VEGF is a therapeutic target for vascular complication in DR and AMD, Dr. Le’s work on the effect of VEGF signaling in the function and survival of retinal neurons are likely to produce mechanistic insights related to the safety and improvementof the off-label use and FDA approved use of anti-VEGF therapies for DR and AMD.

Pathogenic mechanisms of age-related macular degeneration (AMD):AMD is the No. 1 cause of blindness in aged Americans. The recent publications on the relationship between the RPE-derived VEGF and choroidal vascular integrity and the new inducible RPE-specific gene knockout methodology give Dr. Le an edge in the research for atrophic AMD, a disease without clear mechanisms and cure at present.

Preclinical treatment of retinal diseases:A new direction in Dr. Le’s laboratory is to use his unique animal models to explore therapeutic potentials of various strategies for retinal diseases. Dr. Le’s research in this area has been supported by Allergan Inc, a fortune 500 company specializing in ocular diseases. A manuscript describing a study with Allergan on the effect of a FDA approved glaucoma drug on diabetic retinopathy and wet age-related macular degeneration was published in IOVS in 2011, in which Dr. Le is the academic co-corresponding author.