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Fas Ligand enhances vessel maturation and inhibits vascular leakage associated with age-related macular degeneration.
Koirala, Adarsha; Marshak-Rothstein, Ann; Ksander, Bruce R; Gregory-Ksander, Meredith.
Afiliación
  • Koirala A; Schepens Eye Research Institute of Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
  • Marshak-Rothstein A; Department of Medicine, UMass Chan Medical School, Worcester, MA, USA.
  • Ksander BR; Schepens Eye Research Institute of Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
  • Gregory-Ksander M; Schepens Eye Research Institute of Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Res Sq ; 2024 May 08.
Article en En | MEDLINE | ID: mdl-38766158
ABSTRACT
Neovascular age-related macular degeneration (AMD), results from choroidal neovascularization (CNV), retinal edema and loss of photoreceptors. Previous studies suggested that Fas Ligand (FasL) on retinal pigment epithelial cells inhibited CNV by inducing apoptosis of infiltrating Fas+ vascular endothelial cells. However, induction of apoptosis depends on membrane-bound (mFasL) while the FasL cleavage product (sFasL) is neuroprotective. To better understand how FasL regulates the development of CNV, we used a mouse model of laser CNV to evaluate the development of CNV in mice with a FasL cleavage site mutation (ΔCS) and can only express the membrane-bound form of FasL. There was no significant difference in CNV size and area of vascular leakage in homozygous FasLΔCS/ΔCS mice when compared to wild type mice. Unexpectedly, heterozygous FasLΔCS/WT mice developed significantly less vascular leakage and showed accelerated neovessel maturation. However, CNV was not prevented in heterozygous FasLΔCS/WT mice if the Fas receptor was deleted in myeloid cells (FasLΔCS/+ Fasflox/flox CreLysM). Thus, FasL-mediated CNV inhibition depends on the extent of FasL cleavage, and on FasL engagement of Fas+ myeloid cells. Moreover, accelerated neovessel maturation prevents vascular leakage in AMD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
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