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Development of Novel Treatments for Retinal Diseases
The goal of my research is the development of novel treatments for retinal diseases. Due to the normal lack of regeneration and inherent complexity of human neural systems, such as the retina, the combined use of multiple technologies is required for this work. Specifically, we are now exploring the application of bioengineering and gene transfer to stem cell transplantation in the setting of retinal regeneration. Current projects emphasize the transplantation of neural progenitor cell types to the diseased retina, either in the setting of photoreceptor loss or optic nerve injury. These include derivation of a human retinal line from post-mortem tissue, transplantation of animal cells in rodents and large animal models, as well as functional assessment of the visual and immunological consequences of stem cells grafts to the retina. In addition to the use of progenitor cells for cell replacement, current plans center on the genetic insertion of neuroprotective genes into various stem cell lines under the control of a molecular switch. The potential for genetically modified stem cells to rescue retinal neurons is assessed following transplantation to animal models of photoreceptor degeneration and glaucoma.
We are also testing a range of different polymers for their biocompatibility with various progenitor cell populations, in culture, as well as with host eyes of different species in vivo. This work is delineating the effects that polymers have on co-cultured progenitor cells, both before and after transplantation to the retina. It appears that these substrates tend to favor differentiation, enhance cell survival, facilitate graft positioning, and restrict cellular migration. Biodegradable polymer scaffolds therefore provide a useful adjunct to stem cell transplantation in the eye. At this point, selected aspects of our work are close to clinical testing. Because of broad applicability, the list of diseases for which these treatment strategies might be efficacious is extensive. We hope to make a significant difference in the lives of patients with the blinding disease of retinitis pigmentosa, as well as various forms of glaucoma and macular degeneration, together with a long list of devastating but less familiar conditions.
Dr. Lerner’s research interests are focused on the investigations into the pathogenesis and developing new therapeutic strategies for the management of the degenerative and age-related diseases affecting vision, such as age-related macular degeneration and hereditary retinal degenerations. In particular, his lab studies the biology of adult, bone marrow-derived stem cells focusing on their regenerative as well as paracrine (e.g. neuroprotective and neurotrophic) effects and secreted factors, and their therapeutic applications to retinal diseases; cell surface markers of retinal development; and developing stem cell-based therapy for retinal degenerative and age-related diseases. In addition to basic science research, Dr. Lerner is a physician-scientist involved in clinical trials of new therapies for retinal diseases as part of the UCI Eye Institute.
Dr. Lerner completed his PhD in Molecular Biology at the UCLA Boyer Molecular Biology Institute in Los Angeles, CA. He also completed a research fellowship in cell biology at the University of California, San Francisco. In addition, Dr. Lerner completed his internship in Internal Medicine at the University of Southern California Medical Center followed by his residency in Ophthalmology at the Jules Stein Eye Institute at the University of California, Los Angeles. Following his residency, Dr. Lerner completed a two-year fellowship in retinal diseases and surgery at the Cleveland Clinic Foundation in Cleveland, Ohio. Prior to joining the University of California, Irvine School of Medicine, Dr. Lerner was on faculty at the University of Pennsylvania Medical School in Philadelphia, where he was a Scientist at the F.M. Kirby Center for Molecular Ophthalmology and an Instructor in Vitreoretinal Diseases and Surgery.
Donald Minckler, MD and Donald Brown, PhD
Glaucoma represents the second leading cause of blindness worldwide. While both age and intraocular pressure (IOP) are well-recognized risk factors for this disease, the underlying pathologic process involves accelerated death of retinal ganglion cells (RGCs) that is associated with progressive loss of vision. The loss of RGCs has been postulated to occur primarily by injury to axons in the optic nerve head (ONH) due to its anatomic features and the mechanical vulnerability of the lamina cribrosa, the specialized ONH zone comprised of collagen beams that define the channels or pores through which axon bundles exit the eye. The development of confocal microscopy and recent advances in multiphoton microscopy using femtosecond lasers that generate second harmonic (SH) signals from collagen allows for direct optical imaging of the lamina cribrosa. Here, we assess the application of SH generated microscopy (SHG) to the study of the ONH and test the general hypothesis that increasing intraocular pressure in the same eye results in the movement of ONH collagen beams leading to distortion of the lamina cribrosa channels and compression of the axon bundles.
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