Declining vision is among the many problems that afflict the health of seniors. More than 12% of adults aged 65 to 74 told the 2011 National Health Interview Survey that they had suffered vision loss. For those aged 75 and older, this figure rose to over 15%. While doctors are limited in what they can do to address failing eyesight, a recent study suggests that a new treatment method might come from an unexpected source.
RNA and NRTIs
Research published in the November 21, 2014 issue of the journal Science found that drugs used to treat HIV may also be effective against age-related macular degeneration. This report featured contributors from institutions such as the University of Kentucky, the University of Calgary and the University of Southern California. In this case, the medications under the microscope are known as nucleoside reverse transcriptase inhibitors, or NRTIs for short.
For their study, the authors analyzed the impact of these drugs on the vision of mice. The mice’s eyes were infused with genetic material known as Alu RNA. There was a specific reason why this material was chosen; previous research has found that excessive amounts of Alu RNA can cause the death of retinal pigment epithelial (RPE) cells. RPE cells play a key role in our eyes, as they nourish and support the retina while shielding this important tissue layer from damage.
The study opted to use NRTIs due to their effect on reverse transcriptases, a type of enzyme that enables the HIV virus to replicate itself inside the human body. NRTIs help contain the spread of HIV by disrupting this process, appropriately known as reverse transcription. While they are not able destroy the HIV virus, NRTIs can prevent it from using this enzyme to manufacture DNA, serving to keep the virus in check. Since Alu RNA molecules likewise spread via reverse transcription, the authors theorized that such drugs could also hinder Alu RNA’s reproductive capabilities.
Saving Eyes by Blocking Inflammation
After Alu RNA molecules were infused into the eyes of six mice, an NRTI called stavudine was orally administered to these same subjects over a six day period. The rodents were compared against six mice who were given a control treatment instead of the HIV drug. As they had hoped, the authors observed vastly different results among the two groups. The alternative treatment utterly failed to prevent the loss of RPE cells in the control group, with all six mice suffering from RPE cell death. In stark contrast, stavudine was able to keep eye cells from dying in all but one of the mice who received it.
A second experiment reached a similar conclusion about zidovudine, an NRTI injected into the abdomens of mice over a six day span. The nine mice in this group received two injections daily. Zidovudine impeded the death of RPE cells in eight of these rodents, whereas RPE cell loss went unabated in a comparison group.
Though the NRTIs were very successful in preventing the loss of crucial eye cells, their ability to protect RPEs had nothing to do with shutting down reverse transcription. Surprisingly, the two HIV medicines kept eye cells alive by interfering with the inflammasome, a sizable collection of proteins that can induce inflammation within the body. Given this finding, the researchers argue that NRTIs could treat symptoms of “wet” age-related macular degeneration (AMD). An inflammatory disease, wet AMD occurs when blood and other fluids seep out from abnormal vessels, thereby damaging the eye’s macula.
Two upcoming clinical trials plan to document how NTRIs affect the eyes of human subjects. This research will analyze two such medications, one of which is injected directly into the eye and another that is taken orally. The study’s lead author, Jayakrishna Ambati, contends that the impact of the planned trials could be felt relatively soon. If NTRIs are able to shield human eyesight from the ravages of AMD, Ambati believes that they could be used to treat people with this condition in a matter of years.