- Angiogenesis is a
pathological formation of new blood vessels from pre-existing ones.
- Vascular epidermal
growth factor receptor (VEGFR) 2 plays a vital role in angiogenesis.
- Gene editing using adeno-associated
virus CRISPR- Cas9 system showed depletion of VEGFR2 in both in-vitro and in-vivo models.
diseases that result in blindness have a characteristic feature of
there is abnormal production of new blood vessels in the retina. This leads to
rupture, tear and leak of the blood vessels and may result in loss of vision.
Vascular epidermal growth factor receptor (VEGFR) 2 plays an important role in
angiogenesis. Researchers from the Schepens Eye Research Institute of Massachusetts
Eye and Ear have used adeno-associated virus CRISPR system to deplete VEGFR2.
The study is published in Nature Communications.
Angiogenesis in the Eye
intraocular (inside the eye) angiogenesis is a condition where the blood vessels
in the retina (thin layer of tissue on the back inside wall of the eye) begin
to grow abnormally on the surface of the retina. As this progresses, the retina
may swell or the vessels may burst or leak causing distorted vision.
angiogenesis is associated with diseases like proliferative diabetic
retinopathy (PDR)6 retinopathy of prematurity (ROP) and wet age-related macular degeneration
‘The CRISPR-Cas9 system used for gene editing, depleted 80% of VEGFR2 in vitro and 30% in vivo.’
In case of
diabetes, the tiny blood vessels (capillaries) in the back of the eye can
deteriorate and leak fluid into the retina. This causes the retina to swell,
which may blur vision. One may also develop new, abnormal capillaries that
break and bleed.
In macular degeneration, the center of the retina begins to
deteriorate. This causes symptoms such as blurred central vision or a blind
spot in the center of the visual field. There are two types wet macular
degeneration and dry macular degeneration.
are anti-VEGFR like ranibizumab
can reduce neo-vascular
growth and vascular leakage, these approaches require chronic treatment. Also, a significant number of
patients do not respond to the treatment. Scientists believe that targeting
VEGFR2 locus using AAV-CRIPSR/Cas9 may provide a novel alternative approach.
virus (AAV) mediated CRISPR-Cas9 was used to target the VEGFR2 locus. AAVs are
small viruses that are not known to cause any disease. Their vectors show
promise for human gene therapy.
The in-vitro analysis showed that the recombinant AAV
enabled transduction to pathological vessels of mouse primary brain
microvascular ECs (MVECs). 80%
of VEGFR2 expressio as depleted in this case. For in-vivo analysis, eye
diseases characterized by angiogenesis were simulated in mouse models. AAV-mediated
CRISPR-Cas9 edited VEGFR2 showed inhibition of angiogenesis
in two mouse models of oxygen-induced retinopathy and laser-induced choroid neo-vascular growth. 30% of VEGFR2
expression was depleted in-vivo.
The team believes that this approach forms a strong
foundation for treating other angiogenesis associated diseases.Concluding with
the words of the corresponding author, Dr. Lei said "While further study is
needed to determine safety and efficacy of this approach, our work shows that
the CRISPR-Cas9 system is a precise and efficient tool with the potential to
treat angiogenesis-associated diseases."
- Huang, X., Zhou, G., Wu, W., Duan, Y., Ma, G., Song, J., . . . Lei, H. (2017). Genome editing abrogates angiogenesis in vivo. Nature Communications, 8(1). doi:10.1038/s41467-017-00140-3
- Overview - Retinal Diseases - (http://www.mayoclinic.org/diseases-conditions/retinal-diseases/home/ovc-20312856)