Alex Yuan, M.D., Ph.D.

Staff

Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Location:i3-158
yuana@ccf.org
Phone: (216) 444-0079
Fax: (216) 445-2226



The primary goal of Dr. Alex Yuan’s laboratory is to characterize the wound healing response of the

retina and to develop novel methods to repair damaged retina.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.

Studies:

1. A comparison of the retinal microglial cell response to injury in mice and zebrafish. Using a

laser induced injury model, we are comparing the response to injury in mice and in zebrafish. We will

characterize the cellular and the molecular determinants of scar formation in mice and compare those

with determinants of regeneration in fish. In mice, early mobilization of microglia are seen following

laser injury. We hypothesize a similar early response is seen in zebrafish. Our lab is currently working

on constructing a transgenic fish with GFP labeled microglia. In mice, Muller glia are mobilized

following injury and a glial scar is formed. In fish, Muller glia are also activated but they may serve a

different role and may initiate a regenerative program instead of scar formation.

2. Develop novel techniques for targeted delivery to the retina. Our lab is also interested in

developing cell based therapies to deliver molecular to the retina. We are working on a non-invasive

method to target peripheral immune cells to specific locations within the retina. These immune cells

may be modified to deliver molecules to the retina.

3. Cellular response to subthreshold laser lesions.We are characterizing the response of microglia

and macrophages to subthreshold laser lesions that do not cause any structural damage to the retina

and do not initiate scar formation. We will specifically look for changes in the expression of proteins

that may have an effect on vascular permeability.

Innovations:

1. Developed a novel laser induced injury model in zebrafish.In collaboration with the Yuankai Tao

lab, we have developed an OCT-guided laser injury model in the zebrafish retina. The zebrafish retina

is capable of regeneration and the technique is non-invasive, making this a great model for studying

regeneration in a vertebrate in vivo.

In other words ...

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.


Coming soon.


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.