pigmentosa is a degenerative disease that leads to vision loss in humans.
- A novel study has
identified that silencing the Nrl gene could prevent the loss of cells
that occurs due to retinal degenerative diseases
- Dr. Wenhan Yu and
team designed a method to use CRISPR for genetic
disorders associated with vision loss.
is a degenerative disease that leads to vision loss in humans. Though there is
currently no cure for this condition, a novel study has identified that
silencing the Nrl
gene could prevent
the loss of cells that occurs due to retinal degenerative diseases. The study
was published in the journal Nature
and was conducted by scientists from the National Eye Institute
, which is
associated with The National Institute of Health
retina is a tissue that is present at the back of the eye and it consists of
two types of cells, rod photoreceptors and cone photoreceptors. These cells
help in converting the light that enters the eye into electrical signals which
reaches the brain.
Photoreceptors - These cells help in vision in dim light
Photoreceptors- These cells help in vision during well-lit conditions and
are used for color vision.
Retinal Information Network (RetNet
states that there are over 242
genetic mutations with over 202
genes that are associated with the development of various vision associated
, is one such
genetic disorder that leads to a predictable, yet inevitable, course of
disease. This disease is characterized by
- Rod dysfunction
that is characterized by night blindness or a loss in vision during dim
- Rods in the
peripheral retina die leading to a loss in peripheral vision
- Complete blindness
during the late stages of the disease
is currently no available cure for the disease and therapy is mainly used to delay
the progression of the disease. The rods provide nutritional support and
structure for cones, so their dysfunction leads to the death of the cones as
well, resulting in total blindness.
‘Nrl gene codes for neural retina specific leucine zipper protein that is necessary for the development of photoreceptors. Removing this gene prevents the degeneration of the Rod cells.’
of NEI's Neurodegeneration and Repair Laboratory, Dr. Anand Swaroop
, and his team wanted to save vision by saving the
rods from dysfunction.
The Gene Nrl
humans, the Nrl
gene codes for
neural retina specific leucine zipper protein, which is essential for the
development of the photoreceptors.
an earlier study conducted by Dr. Swaroop and colleagues, mice that were grown
without the Nrl gene developed retinas
that had only cones. Nrl
expression is knocked out in mice that are older, according to other studies.
Potential Strategy to Override the Mutations
Swaroop stated that knocking out the Nrl
gene could be a potential strategy to veto the genetic mutations that lead
to rod degeneration. The rods could be guided to become cone like after the Nrl
gene is knocked out. The cones that are present adjacent to these cone like
rods would remain functional.
team of researchers utilized a technique called CRISPR
that acts like molecular scissors to snip
specific DNA sequences with precision. Dr.
, who is the study's first author and an NEI postdoctoral research
fellow, designed a method to use CRISPR in photoreceptors.
steps designed by Dr. Yu were
- The use of an
adeno-associated virus (AAV) as a vector or carrier that could be used to
introduce the CRISPR into the retinal cells.
- The Nrl gene was
removed using CRISPR in wild-type mice, and also in three different mouse
models which suffered from retinal degeneration.
- The retinal cells
were examined along with the gene expression. It was found that rods
developed into cone like cells. These cone like cells were not capable of
detecting light but they helped in the survival of neighboring cells.
was prevention of rod degeneration in mouse models, though the benefit was not
considerable when the therapy was carried out on older animals. Dr. Zhijian Wu,
who was the Head of NEI Ocular Gene Therapy and also the senior author of the
study, said that this method of replacing the defective gene was different from
the conventional gene therapy.
are further research studies that need to be carried before this procedure
reaches the stage of a clinical trial. Studies are yet to prove the safety of
CRISPR and more information is required to prove that there are no adverse
effects. The current study, though, provides considerable support that CRISPR-could be used for genetic disorders
associated with vision loss
study is of particular importance as there is a high prevalence of retinitis
pigmentosa in South India which is evident from a study titled "Prevalence of
retinitis pigmentosa in South Indian population aged above 40 years." Dr. Sen P
and colleagues carried out an ophthalmic examination of 9576 people, both from
rural as well as urban Tamilnadu.
was found that
- 1 in 930 in the urban population had retinitis
- 1 in 372 in the rural population had the condition
- 1 in 4000prevalence in the Western population
alarmingly high level of retinitis
highlights the need to find therapeutic measures which will help
in preventing vision loss and maintaining the patient's quality of life.
- NRL neural retina leucine zipper -
- Genetics of Blindness: Inherited Retinal
Diseases - (http://massgenomics.org/2013/07/genetics-of-blindness.html)
- Prevalence of retinitis pigmentosa in South Indian
population aged above 40 years - (https://www.ncbi.nlm.nih.gov/pubmed/18780262)