Navigation Links
Anti-VEGF Drugs for Retinal Diseases Could Have Serious Side Effects, Scientists Caution

BOSTON, Nov. 3 /PRNewswire/ -- Scientists 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.

Authors of the study include: Magali Saint-Geniez (1,2), Arindel S. R. Maharaj (1), Tony E. Walshe (1,2), Budd A. Tucker (1,2), Eiichi Sekiyama (1,2), Tomoki Kurihara (1), Diane C. Darland (4), Michael J. Young (1,2), Patricia A. D'Amore (1,2,3)

(1) Schepens Eye Research Institute

(2) Department of Ophthalmology, Harvard Medical School

(3) Department of Pathology, Harvard Medical School

(4) University of North Dakota, Grand Forks, North Dakota

Schepens Eye Research Institute is an affiliate of Harvard Medical School and is the largest independent eye research institute in the nation.

SOURCE Schepens Eye Research Institute
Copyright©2008 PR Newswire.
All rights reserved

Related medicine news :

1. Tweens and teens double use of diabetes drugs
2. China Sky One Medical, Inc. Obtains Production Approval for Two New Drugs
3. Tests Could Predict Benefit From Cancer Drugs
4. Cholesterol-lowering drugs may also lower PSA, but whether they cut cancer risk is still not known
5. Topical treatment for cold sores achieves efficacy of oral drugs; represents paradigm shift
6. Common Heart Drugs May Hamper Blood Thinner
7. The Market for Disease-Modifying Osteoarthritis Drugs Will Experience Exponential Growth, Increasing From $477 Million in 2007 to Nearly $3.8 Billion in 2017
8. Albertsons LLC Launches $4.99 Prescription Discount Program Covering Over 500 Generic Drugs
9. Existing anti-obesity drugs may be effective against flu, hepatitis and HIV
10. Cholesterol Drugs May Raise Post-Op Delirium Risk
11. First generation antipsychotic drugs as effective as newer ones in some children
Post Your Comments:
(Date:11/25/2015)... ... , ... On November 23rd 2015 Cozy Products, a division of ... Cozy Products explains what this means for business moving forward. , The Tri Lite ... business model: to sell personal heaters that reduce energy consumption, are economical and keep ...
(Date:11/25/2015)... ... November 25, 2015 , ... Brillianteen, McGaw YMCA’s ... learning in its 65th Anniversary Brillianteen Revue, scheduled for March 4-6, 2016. Auditions ... 65 years, Brillianteen has been a treasured tradition for numerous families in the ...
(Date:11/25/2015)... Missouri (PRWEB) , ... November 25, 2015 , ... ... HEAL, will provide scholarships for people struggling with eating disorders as a result ... from the second annual event, held at Fox Run Golf Club in Eureka, ...
(Date:11/25/2015)... ... November 25, 2015 , ... An unlikely ... resulting in a way for homeless people to have a more dignified and ... new initiative whereby they are repurposing plastic bags into sleeping mats for the ...
(Date:11/25/2015)... ... November 25, 2015 , ... Students and parents have something to be thankful ... Create Real Impact awards. California Casualty is proud to support the contest ... distracted and reckless driving, the number one killer of young drivers. , Almost ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... Nov. 25, 2015  Trovagene, Inc. (NASDAQ: TROV ... that Chief Executive Officer Antonius Schuh, Ph.D., is scheduled ... Annual Piper Jaffray Healthcare Conference. th ... York Palace Hotel in New York ... EST. Mr. Schuh will be available for one-on-one meetings ...
(Date:11/25/2015)... Nov. 25, 2015 USP 800 applies ... preparations (e.g. pharmacists, pharmacy technicians, nurses, physicians, physician ... The chapter also covers all entities which store, ... hospitals, other healthcare institutions, patient treatment clinics, physicians, ... --> --> What is the ...
(Date:11/25/2015)... , November 25, 2015 Developmental, commercial, ... role in boosting the profitability of pharmaceutical products, ... commercial, and regulatory/legal strategies all play a ... says GBI Research . --> ... play a key role in boosting the profitability of pharmaceutical products, ...
Breaking Medicine Technology: