Pea-Sized Telescopic Implant Restores Vision in Patient with Advanced Macular Degeneration

Eye surgeons at my alma mater, UC Davis Medical Center, have managed to successfully implant a new telescope-type implant in the eye of a patient who suffers from end-stage age-related macular degeneration (AMD). AMD is the most advanced form of the macular degeneration and is a leading cause of blindness in older Americans.

These telescope implants were approved by the Food and Drug Administration in 2010, and it is the only medical/surgical option available that can restore at least a portion of the patient’s vision. Eye doctors at the UC Davis Health System’s Eye Center collaborated with the Society for the Blind in this procedure. The UC Davis Health System’s Eye Center is one of the few medical centers in California and the whole nation to offer this innovative procedure.

Mark Mannis, professor and chair of ophthalmology and vision sciences and director of the Eye Center at UC Davis Health System, explained: “Macular degeneration damages the retina and causes a blind spot in a person’s central field of vision. The telescopic implant restores vision by projecting images onto an undamaged portion of the retina, which makes it possible for patients to again see people’s faces and the details of objects located directly in front of them.”

It is presently unclear what causes dry macular degeneration. It clearly forms as the eye ages. Macular degeneration consists of massive die offs of the cells in a particular part of the retina called the “macula.” The macula contains millions of light-sensing cells that provide sharp, detailed central vision, and it is also the most light-sensitive part of the retina. The retina quickly turns light into electrical signals and then sends these electrical signals to the brain through the optic nerve. The brain translates the electrical signals into images. If the macula is damaged, fine points in these images become unclear, fuzzy, spot-ridden, or simply black.

In May 2012, UC Davis cornea specialists Mannis and Jennifer Li implanted the miniature telescope, which is smaller than a pea, in the left eye of a macular degeneration patient names Virginia Bane, who is 89 years old and is from the California town of Pollock Pines, which is near Sacramento. Mrs.Bane is an artist who loves to paint, but has not painted for four years because her eyesight does not allow her to see well enough to do so. Mrs.Bane is the first in Northern California and among the first 50 individuals in the nation to receive this implant.

“I can see better than ever now,” Bane said. “Colors are more vibrant, beautiful and natural, and I can read large print with my glasses. I haven’t been able to read for the past seven years. I look forward to being able to paint again.”

Optometrists from the Society for the Blind and UC Davis occupational therapists have been working with Mrs. Bane to help to learn how to use her implant to its full extent.

“Virginia’s vision will keep getting better and better over time as she retrains her brain how to see. She basically uses her left eye with the telescopic implant to see details, such as using a microwave keypad and reading a book,” said Richard Van Buskirk, who works as an optometrist with the Society for the Blind in Sacramento who specializes in treating patients with low vision. “Her untreated right eye provides peripheral vision, which helps with mobility, such as walking or navigating within her home. Ultimately, her brain will automatically make the shift, using the capability of each eye as needed.”

Retina specialists from UC Davis who treat macular degeneration and other eye disorders associated with the back part of the eye coordinate the treatment program with optometrists who specialize in caring for patients with low vision. Patients are extensively screened before they can participate in this program and undergo medical, visual and functional evaluations to determine if they are good candidates for the procedure.  However, there is a simulator that can show patients what their eyesight might resemble if they were to receive the implant.  This simulator determines if the procedure will actually help the patient see better.

Most candidates for this procedure have very advanced, untreatable eye diseases and include end-stage, age-related macular degeneration (dry form).  All patients must have a disease that is stable and severely impairs vision. Candidates must also be at least 75 years old and have adequate peripheral vision in the eye that will not receive the implant and have no other ocular diseases, such as glaucoma.

A Better Way to Make Induced Pluripotent Stem Cells

Induced pluripotent stem cells (iPSCs) are made from adult cells that have been genetically engineered so that they revert to the stem cell state.  Unfortunately, iPSC production is rather inefficient and it is a long procedure that eats up time.  Are there ways to speed this whole thing up?

Stem cell researchers at Sanford-Burnham have used an unusual strategy to save time and increase the efficiency of iPSC derivation; they used “kinase inhibitors.”  Kinases are enzymes that attach phosphate groups to other molecules.  Placing phosphates on proteins often significantly regulates their activity.  Some proteins are activated when phosphates are attached and others are turned off when phosphates are attached.  As it turns out, kinases are front and center when it comes to the control of cell division.  The scientists at Sanford-Burnham (at UCSD) used chemicals that block the activity of kinases, and this helps generate many more iPSCs than the standard method of iPSC derivation.  This new capability will hopefully facilitate and activate research in many fields that use iPSCs, which includes those who study human diseases and develop new treatments.

Tariq Rana, Ph.D., program director in Sanford-Burnham’s Sanford Children’s Health Research Center and senior author of the study, said: “Generating iPSCs depends on the regulation of communication networks within cells.  So, when you start manipulating which genes are turned on or off in cells to create pluripotent stem cells, you are probably activating a large number of kinases. Since many of these active kinases are likely inhibiting the conversion to iPSCs, it made sense to us that adding inhibitors might lower the barrier.”

Kinase expert, Tony Hunter, Ph.D., who is professor in the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies and director of the Salk Institute Cancer Center, commented: “The identification of small molecules that improve the efficiency of generating iPSCs is an important step forward in being able to use these cells therapeutically. Tariq Rana’s exciting new work has uncovered a class of protein kinase inhibitors that override the normal barriers to efficient iPSC formation, and these inhibitors should prove useful in generating iPSCs from new sources for experimental and ultimately therapeutic purposes.” Hunter was not directly involved with this study.

A graduate student in Rana’s laboratory, Zhonghan Li, was assigned the task of kinase inhibitors that might speed up iPSC-derivation.  Li had some help from some very enterprising scinetists at the Conrad Prebys Center for Chemical Genomics.  Conrad Prebys Center for Chemical Genomics is the Sanford-Burnham’s drug discovery facility, and this center provided Li with a collection of more than 240 chemical compounds that are known to inhibit kinases. Li used the brute-force method of biochemistry by painstakingly adding each chemical, one-by-one, to his cells and then waited to see what happened.  Fortunately, several kinase inhibitors produced many more iPSCs than the untreated cells.  In fact, in some cases, there were so many iPSCs that they outgrew the dish that housed them.  The most potent inhibitors targeted three kinases in particular: AurkA, P38, and IP3K.

Rana and Li worked with the staff in Sanford-Burnham’s genomics, bioinformatics, animal modeling, and histology core facilities.  These valuable resources and their expertise are available to all Sanford-Burnham scientists and also the scientific community at large.  Rana and Li further confirmed the specificity of their findings and even nailed down the mechanism behind one inhibitor’s beneficial actions.

“We found that manipulating the activity of these kinases can substantially increase cellular reprogramming efficiency,” Rana said. “But what’s more, we’ve also provided new insights into the molecular mechanism of reprogramming and revealed new functions for these kinases. We hope these findings will encourage further efforts to screen for small molecules that might prove useful in iPSC-based therapies.”