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Ongoing Projects

Here at the Lee Retina Lab, we are actively engaged in a multitude of ongoing projects focused on advancing treatments for various retinal diseases. These projects encompass innovative approaches such as gene therapies, stem cell research, and nanotechnology, aiming to improve vision and quality of life for patients affected by conditions like macular degeneration, retinitis pigmentosa, and diabetic retinopathy.

Project 1: The Role of Extracellular Vesicles in Retinal Diseases 

  • Proliferative Vitreoretinopathy 

 

Project 2: Developing Extracellular Vesicle-Mediated Intraocular Drug Delivery System ​

  • Bioengineering of Extracellular Vesicles​

  • Active Targeting of Ocular Neovascularization 

  • Active Targeting of Dysfunctional Retinal Blood Vasculature 

  • Active Targeting of Aging Retinal Cells 

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Project 3: Development of Stem-Cell Derived EV Therapy for Retinal Diseases 

  • Dry Age-Related Macular Degeneration 

  • Inherited Retinal Diseases 

  • Diabetic Retinopathy

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Comprehensive Characterization of Extracellular Vesicles

  • Extracellular vesicles from human embryonic stem cell-derived RPE cells were recovered using microfluidic tangential flow filtration and differential ultracentrifugation. We characterized the EVs using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), their tetraspanin expression, and multi-surface epitope heterogeneity.

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Retinal Uptake of EVs

  • Live retinal imaging performed at 3 and 24 h and retina flat-mounts obtained 1 day and 1 week after intravitreal injection of tagged exosomes (orange) show retinal penetration and distribution of EVs.

  • Retinal sections obtained 1 day after intravitreal injection of tagged EVs (ret dots with yellow circles) show that EVs were taken up by both the inner and outer retina.

  • Retinal sections obtained 3 h after systemic injection of tagged EVs (ret dots with yellow circles) via tail vein injection show that EVs were taken up by the retina, suggesting that EVs can cross the blood-retina barrier (BRB).

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ASL Engineered Exosomes

  • CNV in a laser-induced mouse model is confirmed using color fundus photography, fluorescein angiography, OCT, and H&E histology.

  • Integrin 𝛼V expression in CNV lesions is significantly higher than in healthy retina.

  • RGD is one of the major binding ligands for integrin families.

  • ASL-modified EVs, composed of a membrane Anchor (BODIPY - green), Spacer (PEG), and targeting Ligand [cyclic Arg-Gly-Asp (RGD) peptide] show an almost 90% colocalization with integrin 𝛼V (red)

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ASL Engineered Exosomes loaded with miR

  • Clustering of our ASL-modified, miR-loaded EVs showed 4 distinctive clusters: ASL-positive EVs, miR-positive EVs, double-positive EVs, and double-negative EVs.

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