Millions of adults over age 50 struggle each year with vision loss caused by damage to the retina or common macular degeneration.
Physics researchers at The University of Texas at Arlington have developed a new platform that uses ultrafast near-infrared lasers to deliver gene therapy to damaged areas of the retina to enable vision restoration in patients with photo-degenerative diseases.
“Most therapies focus on slowing down or halting degeneration but cannot target already-damaged areas of the retina,” said Samarenda Mohanty, assistant professor of physics and head of UTA’s Biophysics and Physiology Group, who led the research. “Our capacity to specifically target these damaged areas cell by cell opens up a new world of possibilities for vision restoration.”
Mohanty demonstrated the effectiveness of the new method in a recent article published by the Nature journal Light: Science & Applications. In his study, Mohanty and his team compared their ultrafast near-infrared laser-based method of delivering genes with the popular non-viral chemical gene delivery system known as lipofection.
The laser-based method creates a transient sub-mircometer hole that allows the gene for light-sensitive proteins, or opsins, to permeate into the damaged retinal cell. The genes are then activated to produce the opsins, which attach to the cell membrane and convert external light into the photocurrent signals that are basis of sight.
In Mohanty’s experiments, the laser-based method gave better results than chemical gene delivery in terms of the amount of opsins produced and the number expressed on the membrane of the cell. It was also able to target cells one by one where the chemical gene delivery system cannot be that specific.
Furthermore, the laser-based method was also able to effectively deliver large packages of genes encoding a wide spectrum of colors to damaged retinal cells, which could enable broadband vision restoration in patients with photo-degenerative diseases.
With aging populations in many countries, the number of macular degeneration sufferers is expected to reach 196 million worldwide by 2020 and increase to 288 million by 2040, according to The Lancet.
Mohanty is the principal investigator for the research detailed in the article, ‘Optical delivery of multiple opsin-encoding genes to targeted expression and white-light activation.’ The research team included Kamal Dhakal and Subrata Batabyal of the UTA biophysics and physiology laboratory, Weldon Wright of NanoScope Technologies and Young-Tae Kim of UTA’s Bioengineering Department. A National Institute of Health grant supported the initiative.
Earlier this year, Mohanty and UTA Psychology Professor Perry Fuchs published a study in the journal PLOS One that showed how to inhibit pain perception in the anterior cingulate cortex region of the brain. In their optogenetic stimulation method, genes for light-sensitive proteins are delivered to neurons and then activated by a laser.
That study demonstrated that optogenetic stimulation could be more accurate and effective than current methods of delivering stimulation for pain relief. It also enabled the researchers to see how different types of pain activated neurons in the brain’s thalamus.
Alex Weiss, UTA chair of Physics, said “Dr. Mohanty’s team has applied its expertise in the use of light to develop a new technique for effectively introducing genes into living cells. The research could lead to revolutionary new therapies for the restoration of sight in cases that are currently irreparable, but also has applications for the remediation of pain. “
Mohanty joined UTA in 2009 from the Beckman Laser Institute of the University of California, where he did post-doctorate research in in biophotonics. He earned his doctorate in physics from the Indian Institute of Science.
His recent and varied investigations have included mapping neural circuits in the brain, looking at how neuron growth can be controlled in the laboratory and new methods to pinpoint cancer treatment.
Journal References:Kamal Dhakal, Subrata Batabyal, Weldon Wright, Young-tae Kim, Samarendra Mohanty. Optical delivery of multiple opsin-encoding genes leads to targeted expression and white-light activation. Light: Science & Applications, 2015; 4 (11): e352 DOI: 10.1038/lsa.2015.125 Wan Ling Wong, Xinyi Su, Xiang Li, Chui Ming G Cheung, Ronald Klein, Ching-Yu Cheng, Tien Yin Wong. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. The Lancet Global Health, 2014; 2 (2): e106 DOI: 10.1016/S2214-109X(13)70145-1