Navigation Links
Anti-VEGF drugs for retinal diseases could have serious side effects, scientists caution
Date:11/3/2008

Boston, MAScientists at Schepens Eye Research Institute have found that reducing the levels of vascular endothelial growth factor (VEGF), which is best known as a stimulator of new blood vessel growth, in adult mice causes the death of photoreceptors and Muller glia - cells of the retina that are essential to visual function. This finding, published in the November 3, 2008 PLoS ONE, holds implications for the chronic use of promising new anti-VEGF drugs such as Lucentis, which eliminate abnormal and damaging blood vessel growth and leakage in the retina by neutralizing VEGF.

"The take home message of this study is that physicians should be vigilant in monitoring patients undergoing anti-VEGF treatments for any possible signs of these side effects," says Principal Investigator Patricia D'Amore, Senior Scientist at Schepens Eye Research Institute. "Drugs such as Lucentis are very good at reducing the edema (fluids) and eliminating the abnormal blood vessels that characterize wet macular degeneration, but our results suggest that there could be unanticipated side effects."

Scientists have long known that VEGF is essential for normal development of the vascular system and for wound healing. It triggers the formation of new blood vessels that nourish the growing body and heal organs and tissues. VEGF also stimulates--in an apparent misguided attempt to heal perceived damage in the retina--the growth of abnormal blood vessels that leak and damage delicate retinal tissue.

However, a growing body of evidence also indicates that beyond its impact on blood vessel growth, VEGF may play other vital roles in the adult body and eye, so that eliminating the growth factor might lead to unexpected consequences.

Given the popularity and promise of the new anti-VEGF drugs for the treatment of macular degeneration, D'Amore and her team believed that investigating the broader role of this growth factor in the normal adult retina was critical. She and her laboratory mimicked the action of the anti-VEGF drugs by introducing into adult mice a soluble VEGF receptor, known as sFlt1, which binds and neutralizes the VEGF-- in much the same way that Lucentis does in the eye.

After two weeks, the team found no effect on blood vessels of the inner retina, but did find a significant increase in the number of dying cells of the inner and outer nuclear layers which include amacrine cells that participate in transmitting the visual signal; Muller cells that also participate in the visual signal and support the photoreceptors; and, photoreceptors, which are responsible for color and night vision. The team then used electroretinograms to measure visual function and found a significant loss in visual function. Consistent with these observations, they discovered that both photoreceptors and Muller cells express VEGFR2, the major VEGF signaling receptor and they found that neighboring Muller cells express VEGF.

Parallel studies in tissue culture demonstrated that suppressing VEGF in Muller cells led to Muller cell death, indicating an autocrine role for VEGF in Muller cells (i.e. Muller cells both make VEGF and use it for survival). Further, they used cultures of freshly isolated photoreceptors to show that VEGF can act as a protectant for these cells.

"Insight into the complex role of VEGF in the eye and in other parts of the body indicates that increased care should be taken in the long-term use of these drugs and that this new information should be considered in the design of future clinical studies to ensure that these possible side effects are taken into account," says D'Amore.

"Mice eyes differ from human eyes in many ways, so we cannot directly extrapolate these results to humans, but this study is an important heads-up that clinical application of anti-VEGF therapy in the eye needs to proceed with caution," she adds.

From a clinical perspective, Dr. Delia Sang of Ophthalmic Consultants of Boston points out that the use of anti-VEGF therapy in the treatment of patients with wet macular degeneration has revolutionized outcomes in this disease. However, in light of the work of Dr. D'Amore and others, in elucidating possible systemic and ocular side effects of these drugs, "caution must be exercised in identifying patients at increased risk of problems with long-=term VEGF blockade, and potential side effects must be detected early in the assessment of patients who will require repeated dosages of anti-VEGF agents."

The study is also relevant to the drug Avastin, which was initially approved for intravenous use as an anti-angiogenic agent in the treatment of cancer, but is also widely used intravitreally for the treatment of wet AMD because of its similar mode of action and much lower cost.

The next steps in D'Amore's research will include investigating the specific functions of VEGF in the eye.


'/>"/>

Contact: Patti Jacobs
pjacobs12@comcast.net
617-864-2712
Schepens Eye Research Institute
Source:Eurekalert

Related medicine news :

1. Anti-VEGF Drugs for Retinal Diseases Could Have Serious Side Effects, Scientists Caution
2. New review suggests caution on drugs to raise good cholesterol
3. Can cancer drugs combine forces?
4. Study provides hope that some transplant patients could live free of antirejection drugs
5. Study provides hope that some transplant patients could live free of anti-rejection drugs
6. RA Drugs Linked to Slight Skin Cancer Risk
7. Report on patients access to cancer drugs uses flawed methods to reached flawed conclusions
8. Rock N Roll: Sex, Drugs and an Early Exit
9. Australian-led international study shows blood pressure drugs cut death rate in type 2 diabetes
10. Consumer Reports Analysis: Drugs for Nerve Pain, Fibromyalgia Effective, But Not Always Best
11. Are Bargaining Groups Hired by Independent Drugstores Causing Payment Delays to Pharmacies?
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/16/2017)... , ... January 16, 2017 , ... ... been appointed Chief Executive Officer of the medical device company, effective immediately. , ... Robert Storey. “Kevin has a strong track record in medical device market ...
(Date:1/15/2017)... ... 2017 , ... Going above and beyond the practical impact ... communities around the world by offering the Gensuite team and their services to ... members to become involved in a cause that is bigger than themselves and ...
(Date:1/15/2017)... ... 15, 2017 , ... "On Tour is a music themed slideshow production package ... Christina Austin - CEO of Pixel Film Studios. , On Tour’s new slide ... and animation of their slideshows. Place each slide on top of another slide or ...
(Date:1/15/2017)... ... January 15, 2017 , ... The Gravity Vault Indoor Rock Climbing Gym is ... wraps up on the 14,000+ square foot climbing gym, the owners anticipate to open ... in New Jersey and two in New York. With this being its first location ...
(Date:1/14/2017)... ... January 13, 2017 , ... According to a ... Mediterranean diet may lower the risk of type 2 diabetes, Alzheimer’s, and cardiovascular ... health and wellness benefits linked to a Mediterranean diet are only some of ...
Breaking Medicine News(10 mins):
(Date:1/16/2017)... SAN FRANCISCO, Calif. , Jan. 16, 2017 /PRNewswire/ ... that on January 3, 2017 and January 16, 2017 ... the grant of inducement stock options to purchase an ... new employees. These awards were granted pursuant to the ... inducement material to the new employees entering into employment ...
(Date:1/16/2017)... , Jan. 16, 2017 CBDRx, the world,s ... amounts of phyto-nutrient rich hemp extract to Veteran,s groups ... of their proprietary hemp extract to Veteran,s groups across ... best hemp company in the world and through their ... nutritious, full spectrum phyto-nutrient rich hemp extract available. ...
(Date:1/15/2017)... 16, 2017 Le conseil d,administration de ... de collagène pour la régénération de tissus humains, annonce la ... directeur général avec effet immédiat. ... Bill est un dirigeant expérimenté à ... postes de gestion générale et de direction au sein de ...
Breaking Medicine Technology: