Stanford University

Lysosomes in Macular Degeneration

Principal Investigator: Daria Mochly-Rosen

Research Team: Gouri Yogalingam

The work was performed by Dr. Yogalingam at the SENS Research Foundation laboratory in Mountain View and in the laboratory of Professor Daria Mochly-Rosen at Stanford University. Dr. Yogalingam’s work was divided between two projects as follows:

Targeting non-lysosomal enzymes to the lysosomal compartment of retinal epithelial cells

In this project the majority of work has been initiated by the SENS Research Foundation and will continue to be performed at SENS Research Foundation. This will include:

  • Cloning, expressing and purifying recombinantly-expressed enzymes and characterizing their kinetics in vitro.
  • Assessing the uptake and lysosomal targeting of recombinantly-expressed, purified candidate enzymes into cultured mammalian cells, including human macrophage and retinal epithelial cell lines. The majority of this work involved cell biology and biochemical techniques, and was performed at SENS Research Foundation's Research Center. Some imaging (immunofluorescence and electron microscopy) to show that the candidate enzymes are being correctly targeted to lysosomes was done at Stanford.

Developing effective therapies for the treatment of AMD

In this work adeno-associated virus-based vectors will be engineered to contain cDNA encoding candidate enzymes. Retinal epithelial cell lines will be transduced with recombinant AAV containing candidate enzyme cDNAs. The recombinant proteins will be assessed for their correct lysosomal targeting, folding and enzymatic activity towards A2E, an AMD storage product.