title: Heat treatment of retinal pigment epithelium induces production of elastic lamina components and antiangiogenic activity.
abstract: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. In advanced AMD, new vessels from choriocapillaris (CC) invade through the Bruch's membrane (BrM) into the retina, forming choroidal neovascularization (CNV). BrM, an elastic lamina that is located between the retinal pigment epithelium (RPE) and CC, is thought to act as a physical and functional barrier against CNV. The BrM of patients with early AMD are characterized by decreased levels of antiangiogenic factors, including endostatin, thrombospondin-1 (TSP-1), and pigment epithelium-derived factor (PEDF), as well as by degeneration of the elastic layer. Motivated by a previous report that heat increases elastin expression in human skin, we examined the effect of heat on human ARPE-19 cell production of BrM components. Heat treatment stimulated the production of BrM components, including TSP-1, PEDF, and tropoelastin in vitro and increased the antiangiogenic activity of RPE measured in a mouse corneal pocket assay. The effect of heat on experimental CNV was investigated by pretreating the retina with heat via infrared diode laser prior to the induction of CNV. Heat treatment blocked the development of experimental CNV in vivo. These findings suggest that heat treatment may restore BrM integrity and barrier function against new vessel growth.
authors: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.
authors: Eiichi
authors: E
authors: Sekiyama
authors: Magali
authors: M
authors: Saint-Geniez
authors: Kazuhito
authors: K
authors: Yoneda
authors: Toshio
authors: T
authors: Hisatomi
authors: Shintaro
authors: S
authors: Nakao
authors: Tony E
authors: TE
authors: Walshe
authors: Kazuichi
authors: K
authors: Maruyama
authors: Ali
authors: A
authors: Hafezi-Moghadam
authors: Joan W
authors: JW
authors: Miller
authors: Shigeru
authors: S
authors: Kinoshita
authors: Patricia A
authors: PA
authors: D'Amore
mesh_terms: D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016570:Bruch Membrane / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D020256:Choroidal Neovascularization / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004547:Elastic Tissue / Q000378:metabolism / Q000473:pathology; D043169:Endostatins / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006358:Hot Temperature / Q000627:therapeutic use*; D006801:Humans; D054023:Lasers, Semiconductor / Q000627:therapeutic use; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism; D014333:Tropoelastin / Q000378:metabolism; D057135:Wet Macular Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D020533:Angiogenesis Inhibitors; D043169:Endostatins; D005136:Eye Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D015843:Serpins; D019700:Thrombospondin 1; D014333:Tropoelastin; D000099174:Pigment Epithelium-Derived Factor