Rosacea Support Group » VEGF

VEGF and macular degeneration any link to rosacea ?

David Pascoe — Fri, 13 Jul 2007 02:16:44 +0000

It is not only rosacea that is interested in how VEGF affects blood vessels and thus how a disease that is related to blood vessels progresses. The `wet` type of macular degeneration is associated with the growth of abnormal blood vessels. Thus there may well be some common areas of research between rosacea and macular degeneration.

In macular degeneration the blood vessels supplying the macular leak and can lead to scarring that leaves the sufferer with only peripheral vision. Research into angiogenesis (how new blood vessels grow) and VEGF is trying treatments familiar to rosacea sufferers.

Photodynamic Therapy (PDT) was found to not be suitable for all lesions and required ongoing treatment.

Anti-VEGF drugs like Macugen (pegaptanib sodium injection) are also being studied. Macugen is injected into the vitreous fluid of the eye. The drug then prevents VEGF from binding to its receptor and aiding new blood vessel formation.

Other anti-VEGF drugs include Avastin, Lucentis (ranibizumab) and Retaane.

At a high level, angiogenesis appears to be a link between rosacea and several other conditions like cancer – where many cancers require a good blood supply to grow. Perhaps that are other links between rosacea and macular generation that might produce other useful discoveries.

Dr. Sandra Cremers MD is one who is exploring these links ;

My hypothesis is that rosacea is in part caused by new blood vessel growth, angiogenesis, which leads to inflammation and subsequent scar tissue in affected areas. Furthermore, I have hypothesized that patients with rosacea are more likely to get wet macula degeneration compared to patients who do not have rosacea (even when controlling for possible confounders such as sun exposure, family history, and smoking). Additionally, I believe that rosacea may be a marker for increased risk of other types of cancer in the rest of the body. It is possible that rosacea patients are prone to angiogenesis genetically, and thus facilitate the creation of a tumor?s surrounding blood supply.

Dr. Cremers was recently awarded a grant from the NRS ;

Dr. Sandra Cremers, assistant professor of ophthalmology at Harvard Medical School, was awarded $25,000 for a study evaluating the role of angiogenesis (new blood vessel formation) in ocular rosacea. Dr. Cremers will investigate the levels of angiogenesis markers, such as vascular endothelial growth factor (VEGF), in the conjunctiva and eyelids of patients with severe ocular rosacea, compared with normal subjects. She postulates that defining the role of angiogenesis in the development of ocular rosacea may bring focus to future research on this common rosacea subtype, and eventually lead to the development of an effective treatment.

Lets hope that this line of research leads to a whole raft of new discoveries about what, if any, significance VEGF plays in the progression of rosacea.

Update: There is a brief mention of this topic over at the RRDi Forum: Preventing Blood Vessel Growth As Treatment. Dr. Cremers is also a member of the Medical Advisory Committee of the Rosacea Resarch and Development Institute.

Other Articles:

RRF funded study: cathelicidins and VEGF reduced by IPL/PDL

David Pascoe — Thu, 03 May 2007 02:37:00 +0000

The NRS has published on their blog some results from a recently concluded study. The study was titled Structural and biologic changes in the rosacea skin induced by pulse dye laser and intense pulsed light, and was part funded by the now defunct Rosacea Research Foundation.

The study participants were treated with IPL or PDL on one side of their face. I’m not sure that I would be keen to participate in such a study, so I feel grateful to them ! Hopefully they were offered full face treatments at the conclusion of the study, especially given that the study also confirmed that PDL/IPL was an effective treatment !

In the study, the researchers examined biopsies of 10 rosacea patients before and after five received PDL treatment and five IPL treatment for the presence of biochemical components previously associated with rosacea. Each patient received four monthly treatment sessions on one side of the face, with the untreated side serving as a clinical control.

Two of the interesting results from the study ;

Eight of the patients were also found to have elevated cathelicidins, natural antimicrobial agents linked in previous research to rosacea inflammation, and the level was reduced in three IPL- and two PDL-treated patients after treatment.

and

Before treatment the researchers found elevated levels of vascular endothelial growth factor (VEGF), associated with the development of visible blood vessels (telangiectasia), in five of the 10 rosacea patients. In four of these subjects — three in the PDL group and one in the IPL group — the level decreased after therapy.

We know that in 2007 the NRS awarded further grants to Dr. Richard Gallo, and Dr. Kenshi Yamasaki who will continue their research of how cathelicidins, one of the body’s own natural antibiotics, may play a role in the development of rosacea symptoms.

Further Reading ;

NRS announces 2007 research grants

David Pascoe — Tue, 16 Jan 2007 00:53:00 +0000

The National Rosacea Society have announced their latest round of rosacea grants. 5 new grants have been awarded, some as followup to previous grants.

Dr. Cremers will investigate the levels of angiogenesis markers, such as vascular endothelial growth factor (VEGF), in the conjunctiva and eyelids of patients with severe ocular rosacea, compared with normal subjects.

Dr. Richard Gallo, and Dr. Kenshi Yamasaki will continue their NRS-funded research of how cathelicidins, one of the body’s own natural antibiotics, may play a role in the development of rosacea symptoms.

Dr. Richard Granstein will continue research on the role of adenosine triphosphate (ATP), an agent produced by nerves that earlier NRS-funded studies had shown initiates an inflammatory response in human dermal endothelial cells.

Dr. Kent T. Keyser, will study the effects of nicotine on rosacea, to investigate which intracellular signaling pathways are affected and which cellular mechanisms may cause a reaction in rosacea.

Dr. Martin Steinhoff will study the role of neuroimmune interactions in the pathophysiology of rosacea.

Previous National Rosacea Society News:

SPF-90 inhibits VEGF, IL-1a and MMP-1 induced by UVB radiation

David Pascoe — Thu, 09 Mar 2006 07:16:00 +0000

Inhibition of UVB-induced VEGF, IL-1a and MMP-1 release by a SPF-90 sunscreen

Mar Recasens, PhD, Josep Maria Reig, PhD, Carles Trullas, PhD, Carles Pelejero, PhD, Isdin Skin Research Center, Barcelona, Spain

Ultraviolet radiation is well-known to induce a range of deleterious effects on human skin such as photoaging and photoimmunosuppression, and can lead to the development of skin cancer. The UV radiation increases the release of VEGF, IL- 1 alfa and the overexpression of enzymes such as MMP-1. VEGF provides a major angiogenic activity in tumor progression and invasion. IL-1a is a proinflammatory cytokine that stimulates proliferation, differentiation, and activation of various epithelial and endothelial cells, and the production of other cytokines involved in inflammatory skin diseases, histamine release, and systemic and local immunosuppression. The matrix metalloproteinase (MMP) enzymes are responsible for breaking down macromolecules of the skin ECM; in particular, MMP-1 can hydrolyze type I and III collagen, and seems to play a crucial role in the disorganization and progressive degeneration of dermal ECM. We used human skin equivalents to study the efficiency of a SPF-90 sunscreen in preventing the VEGF, IL-1a and MMP-1 release induced by UVB radiation. Skin equivalents, either treated or untreated with SPF-90 sunscreen at 2 mg/cm2, were exposed to 300 and 600 mJ/cm2 of UVB. To assess the UVB-induced damaging effects, we investigated the following events 24 hours after UVB irradiation: VEGF, IL-1 IL-1a, and MMP-1 release in the culture medium by ELISA and cell viability. The results of this study reveal that the unprotected UVB-irradiated skin equivalents show increased VEGF, IL-1 IL-1a, and MMP-1 release, and decreased cell viability. In contrast those skin equivalents treated with sunscreen show a significantly lower VEGF, IL-1 IL-1a, and MMP-1 release and higher cell viability. We concluded that this SPF-90 sunscreen provides an efficient protection against UVB-induced VEGF, IL-1 IL-1a, and MMP-1 release.

Author disclosure: Researcher at Isdin Skin Research Center. 100% sponsored by Isdin Skin Research Center.

Poster Discussion Session P2610, American Academy of Dermatology, 64th Annual Meeting, March 3-7 2006, San Francisco.

Supplement to Journal of The American Academy of Dermatology, March 2006, Volume 54, Number 3.

JAAD Poster Abstracts Online (29Mb)
Poster Session Online

Related Articles:

VEGF and vasodilation

David Pascoe — Fri, 23 Sep 2005 00:00:00 +0000

An in-depth article to do with the effect of VEGF on the vasodilation and vasorelaxation of blood vessels.

Vasodilator effect and mechanism of action of vascular endothelial growth factor in skin vasculature

American Journal of Physiology Heart and Circulatory Physiology 286: H946-H954, 2004.

Abstract: Various laboratories have reported that local subcutaneous or subdermal injection of VEGF₁₆₅ at the time of surgery effectively attenuated ischemic necrosis in rat skin flaps, but the mechanism was not studied and enhanced angiogenesis was implicated. In the present study, we used the clinically relevant isolated perfused 6 x 16-cm pig buttock skin flap model to 1) test our hypothesis that VEGF₁₆₅ is a potent vasodilator and acute VEGF₁₆₅ treatment increases skin perfusion; and 2) investigate the mechanism of VEGF₁₆₅-induced skin vasorelaxation.

retinaldehyde may reduce VEGF

David Pascoe — Thu, 18 Aug 2005 02:18:00 +0000

From Skin and Allergy News, July 2005, Think Outside the Box for Rosacea Tx Options.

Cherie Detrie, M.D., director of cosmetic dermatology at the University of Pennsylvania in Radnor, said

“the retinaldehyde offers rosacea patients who may have sensitive skin the benefits of retinoids with fewer side effects.”

She described the formulation as a “way station” between retinol and retinoic acid.

“Research demonstrates that retinaldehyde, like retinoic acid, produces dose-dependent epidermal thickening, reduction of the stratum corneum, and increased keratinocyte turnover. Importantly for rosacea, it may also reduce vascular endothelial growth factor (VEGF), which has neoangiogenic and inflammatory properties in the skin.”

Retinaldehyde is made by Pierre Fabre Dermo-Cosmetique, which sponsored Dr. Detrie’s talk.

VEGF and vasodilation