Alex Yuan, M.D., Ph.D.
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 444-0079
Goals & Projects
The primary goal of Dr. Alex Yuan’s laboratory is to characterize the wound healing and regenerative response of the retina and to develop novel methods for retinal repair. The retina is comprised of a multi-layered, complex network of neurons that receive light stimuli and transmit that information to the brain. In response to mechanical, chemical, or photic damage, the retina forms scar tissue, which interrupts the normal connections between neurons. This disruption is permanent and once vision has been compromised, it cannot be restored. However, there are some organisms such as teleost fish that are capable of retinal repair following injury. Our lab is studying the retina repair process following laser induced retinal injury in fish. We hypothesize that there are molecular pathways that are modified or lost in mammals which, if restored, may allow the mammalian retina to regenerate or may facilitate the reintegration of transplanted cells into the normal retina.
- Characterize the role of the leukocyte adhesion molecule, Alcama, during zebrafish retinal regeneration.Our lab studies retinal regeneration in zebrafish using a targeted laser injury model. Using this model, we are able to precisely place lesions in the retina. Laser injury has a benefit of selectively damaging the outer retina and is also desirable due to its rapid and facile application compared to other methods. Following outer retina (photoreceptor) injury, Muller glia rapidly proliferate and some of the resulting daughter cells migrate from the inner nuclear layer to the outer nuclear layer to replenish the damaged photoreceptors. The remaining Muller glia start to express the cell surface protein, Alcama in response to injury. During development, Alcama plays a role in axonal guidance and cellular migration. We hypothesize that Alcama plays a similarly important role during retinal regeneration in zebrafish. Interestingly, using a similar mouse model, we were unable to detect Alcama expression following injury. We are currently characterizing the role of Alcama in zebrafish and look to determine if Alcama can aid in facilitating retinal regeneration in mice and other mammals.
- Optic nerve regeneration model.In addition to our work on retinal regeneration, we are also collaborating with Dr. Frank Papay’s laboratory on developing an ocular transplantation model. The first step in this process is to successfully establish optic nerve regeneration following the complete transection of the optic nerve. We have developed a method to maintain the retina blood flow while completely transecting the optic nerve and are currently evaluating different small molecules that may facilitate the regrowth of axons through the injury site.
- Evaluation of a novel self-assembling hydrogel for sustained intravitreal drug delivery.In collaboration with Dr. Vivek Kumar’s group (New Jersey Institute of Technology), we are evaluating the anti-angiogenic properties of a self-assembling hydrogel and its ability to promote sustained delivery of bevacizumab (Avastin) and steroids using a rat model of retinal neovascularization.
In humans and other mammals, the adult retina has lost its ability to repair itself after injury. In contrast, more primitive vertebrates such as fish are capable of retinal repair and regeneration. Our laboratory aims to understand the cellular and molecular basis for this difference in hopes of developing new therapeutic tools for retinal repair.
Dhoot D.S. et al. Evaluation of choroidal thickness in retinitis pigmentosa using enhanced depth imaging optical coherence tomography. Br J Ophthalmol Oct 23, 2012 (epub ahead of print).
Yuan A., Ehlers J.P. Crystalline retinopathy from primary hyperoxaluria. Retina 32,1994-5, 2012.
Steinle N.C. et al. Oral rifampin utilization for the treatment of chronic multifocal central serous retinopathy. Br J Ophthalmol 96, 10-13, 2012.
Yuan A., Kaiser P.K. Emerging therapies for the treatment of neovascular age related macular degeneration. Seminar in Ophthalmology 26, 149-155, 2011.
Yuan A., Singh R.P. Radiation maculopathy treated with intravitreous ranibizumab. Journal of Clinical and Experimental Ophthalmology 2, 2011.
Yuan A., Singh R.P. Ranibizumab for the treatment of macular edema following retinal vein occlusion. Clinical Investigation 1, 1445-1454, 2011.
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