Investigation of Novel Pathogenesis and Therapeutic Strategy of AMD

Haijiang Lin, MD, PhD
University of Massachusetts Medical School (Worcester, MA)

Co-Principal Investigators

Bo Tian, PhD
Year Awarded:
2019
Grant Duration:
July 1, 2019 to June 30, 2021
Disease:
Macular Degeneration
Award Amount:
$200,000
Grant Reference ID:
M2019074
Award Type:
Standard
Award Region:
US Northeastern
Haijiang Lin, MD, PhD

Cytosolic Accumulation of Nuclear DNA fragments in Retinal Pigment Epithelium and Age-Related Macular Degeneration

Summary

Age-related macular degeneration is the leading cause of irreversible vision loss among elderly people in developed countries. The “dry” form of AMD accounts for 85% of all cases without effective treatment, while the “wet” form occurs in about 15% of the advanced AMD cases, which is being treated with anti-VEGF but not effective in all cases. Our study will identify the factor(s) contributing to the progression of AMD and explore method to halt or reverse AMD retinal lesion. Overall goal is to gain a better understanding of the molecular mechanism of this disease and to develop novel effective therapies.

Details

The goal of our project is to explore novel gene therapy strategies and investigate the molecular mechanisms for the progression of age-related macular degeneration (AMD). During the progression of AMD, a small retina lesion gradually expands to a large lesion.  We have found that the sick retinal pigment epithelial (RPE) cells can secrete factors that make the neighboring healthy RPE cells dysfunctional and promote the progression of AMD. Our first aim will be to isolate and identify these factors. Our second aim will be to use an Adeno-Associate Virus (AAV) vector to deliver a gene intended to rescue the retina or block the AMD-like pathology. To date, our research has been unique because it will explore the molecular mechanism for AMD progression and novel gene therapy strategies to halt the progression of AMD. A successful gene therapy for AMD has not been trialed before, therefore our research has exciting potential for patients suffering from this debilitating condition. By identifying new factors responsible for the progression of AMD, we will also inspire future research. 

About the Researcher

Haijiang Lin MD, PhD, serves as Director of the Translational Research Center within the Department of Ophthalmology and Visual Sciences at the University of Massachusetts Medical School as well as an investigator at Massachusetts Eye and Ear Infirmary at Harvard Medical School. Dr. Lin earned his PhD in molecular biology and biochemistry at McGill University and received research postdoctoral training at the Dana-Farber Cancer Institute at Harvard Medical School and Whitehead Institute for Biomedical Research at MIT. He completed his ophthalmology training at the University of Texas Residency Program followed by the Massachusetts Eye and Ear Medical Retina Fellowship Program.  Dr. Lin’s clinical expertise lies in the diagnosis and treatment of diabetic retinopathy, age-related macular degeneration (AMD), and other retinal vascular diseases. As a clinician-scientist, Dr. Lin’s lab primarily focuses on epigenetic mechanisms of disease, gene-editing, and stem cell tissue regeneration, as well as gene therapy approaches for AMD and diabetic retinopathy. To date, Dr. Lin has identified several genes involving ubiquitin conjugation and de-ubiquitination, created a de novo DNA methyl-transferase gene knockout and induction mice, and studied the function of DNA methylation in tumor formation. He demonstrated the function of microRNA in the development of AMD before people cast eyes over this non-coding RNA in this field, and was one of the pioneers who found that mitochondrial DNA (mtDNA) damage is associated with AMD. and is currently exploring gene therapy using adenoviruses and non-vial vectors for the treatment of inherited retinal diseases like AMD.  

Personal Story

As a clinician, I have seen many patients with age-related macular degeneration (AMD). One that stands out in my mind is a 65-year-old woman diagnosed with early-onset AMD for the first time in my clinic. When she began to cry and share her family historyI learned that both her parents had suffered from advanced age-related macular degeneration and eventually lost all independence, relying on others for all activities of daily living. My patient had already suffered so much and was no different from so many other patients with a genetic predisposition for AMD that either present to my clinic too late or fail to respond to current treatments. I feel truly heartbroken for these patients and feel optimistic that with my strong background in molecular biology and biochemistry we should identify on a more microscopic level the mechanisms of AMD and work to correct aberrancies by identifying new therapeutic targets and changing the expression of genes. Your funding will not only support this promising research but also train young scientists in my laboratory, the vehicles necessary for future innovation in this field.

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