Collaboration between scientists from mainland China, the University of California, San Diego School of Medicine and Shiley Eye Institute have developed a new, stem cell-based technique that permits remaining stem cells to regrow functional lenses after the diseased lens was removed. This treatment was initially tested in laboratory animals, but it has now been tested in a small human clinical trial. This procedure produced far fewer surgical complications than the current standard-of-care. The real boost is that this regenerative procedure resulted in regenerated lenses that had superior visual qualities in all 12 of the pediatric cataract patients who served as subjects for this clinical trial.
Kang Zhang, MD, PhD, chief of Ophthalmic Genetics, founding director of the Institute for Genomic Medicine and co-director of Biomaterials and Tissue Engineering at the Institute of Engineering in Medicine, both at UC San Diego School of Medicine, said: “An ultimate goal of stem cell research is to turn on the regenerative potential of one’s own stem cells for tissue and organ repair and disease therapy.” Zhang and his colleagues published their work in the journal Nature.
Cataracts are cloudiness over the lens of the eye that blurs vision. The lens consists mostly of water and protein. When the protein aggregates, it clouds the lens and reduces the light that reaches the retina. This clouding may become severe enough to cause blurred vision. Most age-related cataracts develop from protein clumpings. You do not have to be older to suffer from cataracts. Congenital cataracts occur at birth or shortly after birth. Scarring of the retina or prenatal damage to the eye can cause congenital cataracts. Congenital cataracts are a significant cause of blindness in children. Current treatment for congenital cataracts is limited by the age of the patient. Most pediatric patients require corrective eyewear after cataract surgery.
To address this medical need, Zhang and colleagues examined the regenerative potential of endogenous stem cells on the lens. Unlike other stem cell approaches that involve creating stem cells in the lab and introducing them back into the patient, Zhang decided to use stem cells that are already in place at the site of the injury to do the heavy lifting. In the human eye, lens epithelial stem cells or LECs generate replacement lens cells throughout a person’s life, even though their production declines with age.
Unfortunately, current cataract surgeries essentially remove LECs within the lens. Whatever cells might be left over produce disorganized regrowth in infants and no useful vision. Zhang and his colleagues first confirmed that LECs had regenerative potential. To confirm this, they used laboratory animals. With that knowledge in hand, Zhang and his collaborators devised a novel, minimally invasive surgical procedure that removes the cloudy lens, but manages to maintain the integrity of the membrane that gives the lens its required shape (the lens capsule). With the lens capsule in place, the LECs were activated to replace the missing lens.
Once again, Zhang and his team ensured that their technique worked in animals before they ever tried it on a human patient. Animals with cataracts whose lenses were extirpated, but whose lens capsules were left intact, regenerated new lenses that were devoid of cataracts and provided excellent sight. With their technique honed and ready, Zhang and others tested their procedure on very young human infants in a small human trial. They discovered that their new surgical technique allowed pre-existing LECs to efficiently regenerate functional lenses. In particular, the human trial involved 12 infants under the age of 2 treated with the new method developed by Zhang and others, and 25 similar infants receiving current standard surgical care.
The results were stark: the control group experienced a higher incidence of post-surgery inflammation, early-onset ocular hypertension and increased lens clouding, but those infants who received Zhang’s new procedure showed fewer complications and faster healing. After three months, the 12 infants who underwent the new procedure had a clear, regenerated biconvex lens in all of their eyes.
“The success of this work represents a new approach in how new human tissue or organ can be regenerated and human disease can be treated, and may have a broad impact on regenerative therapies by harnessing the regenerative power of our own body,” said Zhang.
Zhang indicated that he and his colleagues are now looking to apply what they learned in this project to tackling the issue of age-related cataracts. Age-related cataracts are the leading cause of blindness in the world. Over 20 million Americans suffer from cataracts, and more than 4 million surgeries are performed annually to replace the clouded lens with an artificial plastic lens (intraocular lens).
Despite technical advances, a large portion of patients undergoing surgery are left with suboptimal vision post-surgery and are dependent upon corrective eyewear for driving a car and/or reading a book. “We believe that our new approach will result in a paradigm shift in cataract surgery and may offer patients a safer and better treatment option in the future,” said an optimistic Zhang.
Source: Stem Cells Regenerate Human Lens After Cataract Surgery and Restore Vision