Stemming Vision Loss With Stem Cell Therapy: The California Project to Cure Blindness

byy Dennis Clegg, PhD, Professor, department of molecular, cellular and developmental biology and co-director of the UCSB Center for Stem Cell Biology and Engineering

 

Age-related macular degeneration (AMD)-a leading cause of blindness in the elderly-takes a devastating toll on quality of life by robbing those affected of their fine visual acuity in the central visual field.

 

While the development of vascular endothelial growth factor (VEGf) inhibitors has provided an effective therapy for many with the exudative or "wet" form of the disease, this patient population only accounts for approximately 10 percent of

 

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those affected. For the majority of patients with the non-exudative or "dry" form, no efficacious treatment exists. Ongoing efforts at UCSB in collaboration with other institutions are aimed at developing a stem cell-based therapy for dry AMD.

 

Recent advances in AMD research have shown that loss of vision in most cases is due to the death of the retinal pigmented epithelium (RPE), which in turn gives rise to loss of photoreceptors. The RPE is a pigmented monolayer behind the retina that performs crucial functions that support photoreceptors.

 

RPE deficits are linked to chronic inflammation and complement attack; accumulation of toxic compounds within RPE; or loss of RPE attachment.

 

Studies in both rodents and humans have shown that if the diseased RPE can be replaced by healthy tissue, photoreceptors can be preserved. Recent studies have demonstrated that human embryonic stem cells and induced pluripotent stem cells can differentiate into RPE that is functional in animal models.

Retinal pigment epithelial cells derived from human embryonic stem cells stained with an antibody
to the tight junction
protein Zo-1 (in green)
and for nuclei (in red).
Photo by Sherry Hikita

 

 

 

  

 

Early stage retinal cells derived from human embryonic stem cells stained for Pax6 (red)
and nuclei (blue).
Photo by David Buchholz

 

 

 

  

 

 

Human embryonic stem cells grow in "colonies" like the one pictured above.
Photo by David Buchholz

 

Developing Clinical Applications

The California Project to Cure Blindness is an interdisciplinary research effort involving researchers at UCSB in the  Center for the Study of Macular Degeneration and the Center for Stem Cell Biology and Engineering, along with retinal surgeons in the Keck School of Medicine at the University of Southern California (Mark Humayun, principal investigator), materials chemists at Caltech, and experts in cellular therapy from the city of Hope and University College London. The goal is to differentiate a monolayer of RPE on a synthetic substrate that can be implanted in the macula to replace damaged RPE and therefore preserve photoreceptors.

 

The eye is an excellent candidate for developing such a therapy. It is accessible via well-developed surgical methods, and excellent methods can be utilized for noninvasive imaging and assessment of endpoint parameters to measure visual acuity. Furthermore, relatively few cells are necessary to cover the macular region.

 

To successfully move stem cell research from the laboratory to the clinic will require standardized production of a reliable RPE graft with proven efficacy in animal models. Despite the many challenges associated with developing such a novel therapy, the interdisciplinary team, with funding from the California Institute for Regenerative Medicine, has a goal of filing an investigational new drug application with the FDA within four years. The hope is to perfect this new technology to alleviate suffering for the millions of people affected by dry AMD.

 

To learn more about the work of The California Project to Cure Blindness to prevent vision loss and improve the quality of life for those suffering from age-related macular degeneration, visit www.thecaliforniaproject.org.