Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies.
An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice
Mice deficient in monocyte chemoattractant protein-1 or its cognate C-C chemokine receptor-2 develop cardinal features of age-related macular degeneration, including accumulation of lipofuscin in and drusen beneath the retinal pigmented epithelium.
Drusen complement components C3a and C5a promote choroidal neovascularization.
Mechanisms of Age-Related Macular Degeneration
DICER1 Loss and Alu RNA Induce Age-Related Macular Degeneration via the NLRP3 Inflammasome and MyD88
Sequence- and target-independent angiogenesis suppression by siRNA via TLR3
It is shown that generic siRNAs might treat angiogenic disorders that affect 8% of the world’s population, and that si RNAs might induce unanticipated vascular or immune effects.
Macrophage depletion inhibits experimental choroidal neovascularization.
- E. Sakurai, A. Anand, B. Ambati, N. Van Rooijen, J. Ambati
- Medicine, BiologyInvestigative Ophthalmology and Visual Science
- 1 August 2003
The role of the macrophage is defined as a critical component in initiating the laser-induced CNV response and reduction in CNV volume correlated with VEGF protein levels and number of infiltrating macrophages.
DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration
Findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness.
Corneal avascularity is due to soluble VEGF receptor-1
It is shown that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous V EGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice.
Immunology of age-related macular degeneration
The diverse immune cell types, inflammatory activators and pathways that are involved in AMD pathogenesis are outlined and the future of inflammation-directed therapeutics to treat AMD in the growing aged population is discussed.