Researchers from University of Kentucky College of Medicine have identified an RNA-based mechanism in the retina that could be responsible for triggering the blindness associated with advanced dry age-related macular degeneration (AMD). The article has been published in Nature.
Unlike wet AMD, which results from scarring caused by leaky blood vessels and thus can be treated with a variety of angiogenesis inhibitors, dry AMD is initially characterized by the buildup of extracellular debris beneath the retina. Over time, those deposits cause significant atrophy of the retinal pigment epithelial (RPE) layer—a condition known as geographic atrophy—leading to loss of photoreceptors in the macula, the central and the most important part of the retina, which can ultimately advance to permanent blindness.
Although difficult to predict, dry AMD can turn into wet AMD at any time during disease progression. There are no medical or surgical treatments for dry AMD.
To find potential targets for geographic atrophy, Dr Jayakrishna Ambati and colleagues initially looked at levels of proteins and nucleic acids in eye samples from dry AMD patients. The researchers found that levels of the microRNA-processing enzyme dicer 1 ribonuclease type III (DICER1) were significantly lower in patient eyes than in non-AMD control eyes (p=0.0036). DICER1 levels were unchanged in the RPE layer of human eyes with other retinal diseases, suggesting that low DICER1 could be a specific marker of geographic atrophy.
The team next generated Dicer1 knockout mice to recapitulate the geographic atrophy phenotype in animals. All the Dicer1 knockouts showed degeneration of the RPE layer compared with wild-type littermate controls.
Subsequent studies in human RPE cells and mice revealed the specific mechanism by which low DICER1 levels led to degeneration of the RPE cells or layer, respectively. The decrease in DICER1 caused the accumulation of cytotoxic Alu RNA molecules in the RPE layer, where they caused degeneration of tissues making up the retina and macula.
Alu RNAs are retrotransposon sequences that exist throughout the human genome but do not code for proteins. Considered to be a toxic type of RNA that play a disease-causing role in a large section of the human genome, these Alu-related elements make up 11 percent of the human genome. They were considered "junk" DNA because researchers did not understand their role, but are now considered to play a crucial role in the death of retinal cells in those with geographic atrophy
In cultured human RPE cells with low DICER1 levels, antisense oligonucleotides targeting Alu RNA significantly blocked RPE cellular degeneration compared with control oligonucleotides (p<0.05).
Simply said, in patients with geographic atrophy, reduction of the Dicer enzyme in the retina leads to accumulation of Alu RNA, which leads to death of the retina.
The team has also developed two therapies that may prevent geographic atrophy. The first therapy increases Dicer levels in the retina by "over-expressing the enzyme", while the second therapy blocks Alu RNA with a drug that clings to the toxic structure and degrades it. Based on experiments performed in the laboratory, both therapies could efficiently prevent geographic atrophy.
The University of Kentucky has filed for patents on both therapies, and clinical trials are expected to begin by the end of this year.
my mother is able to see things clearly from side vision but not from centr vision..
ReplyDeleteOn Amsler recording the obaservation were as follows--
1) When she is trying to see the the center spot it is not visible, sometimes some straight lines are seen near the spot..
She can see square boxes around the center but not in the center.
2) the spot is not visible..saometimes it comes other times it is invisible.mostly it is invisible
There is no black spot in the center vision , she can just se the whicte background with no black spot in the center.
3)All the visible lines are straight and parallel . they are of equal and square
After searching the internet the problem is looking of Dry AMD with low central vision .
She cant recognise objects from the center vision , but she can if she loks from side vision , but it takes time,.
The above was done without glasses.
But with glasses she was able to see more of the spot , a few lines from left radius of central vision was invisible..Sometimes the spot is visible other times not.
Well my obserations were that using glasses it was more visible but the roblem still exists.
But the glasses are correctly not of her vision .
It is about 5 years she is sufferingfrom this problem.
We would be highly oliged of your suppport.
Sir atleast we are expecting to get correct glasses , so that watever she sees , atleast that would be clear.
And sir we want to get her into geting low vision aid ..Please help