Endostatin, which demonstrates potent anti-angiogeneic activity, could be a potential therapeutic agent for treating age-related macular degeneration (AMD), according to a new research article published in the latest issue of the journal of the Federation of American Societies for Experimental Biology.
Endostatins are broad-spectrum, anti-angiogeneic agents derived from the basement membrane component, collagen XVIII. Alexander G. Marneros, a leading scientist at the Department of Developmental Biology, Harvard Medical School, Massachusetts, USA, and colleagues conducted a study to evaluate the effect of endostatin in inhibiting choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD).
They treated ‘XVIII/endostatin lacking mutant mice’ and ‘control mice’ with laser to create vascular injury and induce CNV. The mutant mice exhibited an increased vascular leakage, and up to 3-fold larger CNV lesions compared to control mice, irrespective of the age-related changes at the choroid-retina interface. Administration of recombinant endostatin reduced CNV lesions significantly in both ‘mutant mice’ and ‘control mice’. The study results, demonstrating the potent anti-angiogeneic activity of endostatin, point towards an effective treatment for regulating CNV growth and vascular leakage.
Age-related macular degeneration (AMD) is one of the leading causes of blindness in the western world, commonly affecting people over 65 years of age. Choroidal neovascularization (wet macular degeneration) is characterized by the growth of new blood vessels originating from the choroid (layer of blood vessels and connective tissue between the sclera and retina) into the subretinal space. Age, genetic make-up, and smoking are some of the major risk factors of AMD. Endostatin interferes with the angiogenesis activity of growth factors like vascular endothelial growth factor (VEGF), a prominent angiogenic molecule, that plays a major role in the development of CNV.
Tatar and colleagues (Eye Experimental Research, 2006) had analyzed the expression of endostatin (angiogenic inhibitor) in seven donor eyes (control) and the choroidal neovascular membrane (CNV) removed from 36 different patients. They demonstrated the presence of high concentrations of endostatin in choroidal vessels and retinal pigment epithelium (RPE)-Bruch’s membrane complex in donor eyes without CNV. Based on the result, researchers suggested that endostatins, detected in high concentrations in CNV, plays a vital role in inhibiting neovascular AMD, and its exogenous administration could potentially make a novel therapy in treating neovascular age-related macular degeneration.
Pegaptanib sodium (Macugen | Pfizer) and ranibizumab (Lucentis | Genentech) are the anti-VEGF drugs currently available for managing neovascular AMD. Azad and colleagues have reported the economic limitations of these drugs in the latest issue of Indian Journal of Ophthalmology. These drugs also necessitate regular and long term intravitreal administration and are not cost-effective. Bevacizumab (Avastin | Genentech), although affordable, is not approved for treating neovascular AMD. These limitations increase the demand for newer anti-VEGF drugs, and further research on endostatin-based treatment strategies for neovascular AMD and related disorders hold great potential.
References
1. Marneros AG, She H, Zambarakji H, et al. Endogenous endostatin inhibits choroidal neovascularization. FASEB. 2007; 21:3809-3818.
2. Tatar O, Shinoda K, Adam A, et al. Expression of endostatin in human choroidal neovascular membranes secondary to age- related macular degeneration. Experimental Eye Research. 2006 August; 83(2): 329-38.
3. Azad R, Chandra P, Gupta R. The economic implications of the use of anti- vascular endothelial growth factor drugs in age- related macular degeneration. Indian Journal of Ophthalmology. 2007 November-December; 55(6): 441-3.
