Cell Based Neurotrophin Therapy for Glaucoma
Glaucoma is a blinding disease characterized by the progressive loss of retinal ganglion cells. One major line of therapeutic intervention being developed for glaucoma is the introduction of growth factors that can prevent the death of the ganglion cells. Two major hurdles in this area of investigation is that we have not been able to deliver more than one or two factors at a time and we can not deliver them for long enough periods. Evidence suggests that the most effective treatment would be the delivery of multiple factors for periods of several months to years. A possible solution to these problems is the use of progenitor cells. These cells are similar to stem cells in that they are undifferentiated and can self renew or divide in culture. These cells can be used as transplants in damaged nerve tissue, where they can infiltrate the regions of damage and make contact with living neurons. Another advantage of these cells is that we can alter them in the laboratory to express and secrete the complex mixture of growth factors that ganglion cells need to survive. Once transplanted into the eye, we hypothesize that they will make contact with surviving ganglion cells and provide them with the critical growth factors needed for survival. Lastly, we expect that these cells will provide the growth factor support for extended periods of time without any additional treatment. Using progenitor cells for this 'cell based therapy' is a relatively new concept for treating glaucoma. This proposal is designed to address some of the fundamental questions we need to answer to pursue this line of therapy. Among the questions we will address are: * Where do the cells go when injected into the vitreous cavity - do they penetrate the retina and make contact with the target ganglion cells? * How long do the cells survive in the retina? * Can these cells attenuate the rate of ganglion cell loss when engineered to secrete a single growth factor known to promote ganglion cell survival? To answer these questions, we propose to study their effects on mice that spontaneously develop glaucoma as they age. If successful, we propose to extend these studies by altering these cells further to secrete a potent mixture of growth factors required for maximal ganglion cell survival.
Nickells, R. W. (1999) Apoptosis of retinal ganglion cells in glaucoma: an update of the molecular pathways involved in cell death. Surv Ophthalmol. 43 Suppl1: S151-161.
Li, Y., Schlamp, C., and Nickells, R. (1999) Experimental induction of retinal ganglion cell death in adult mice. Invest Ophthalmol Vis Sci. 40(5):1004-1008.
Nickells, R.W. and Zack, D.J. (1996) Apoptosis in ocular disease: a molecular overview. Ophthalmic Genet. 17(4):145-165.
First published on: June 10, 2008
Last modified on: June 11, 2008