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Publication Detail
Integrins αvβ3, and αvβ5, are selectively expressed in active human retinal and choroidal neovascular membranes
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Friedlander M, Theesfeld CL, Sugita M, Thomas MA, Chang S, Coll G, Fruttiger MA, Richardson WD, Brooks PC, Cheresh DA
  • Publication date:
  • Journal:
    Investigative Ophthalmology and Visual Science
  • Volume:
  • Issue:
  • Status:
  • Print ISSN:
Purpose: We have described two angiogenic pathways defined by distinct αv, integrins and that these pathways are potently inhibited in a corneal micropocket model by antibody or peptide antagonists to αvβ3, or αv,β5 integrins (Science, 270:1500, 1995). In this study we (1) examine human retinal and choroidal neovascular (NV) membranes for the expression of αvβ3, and αvβ5 and (2) use peptide antagonists of these integrins to inhibit retinal blood vessel growth in a mouse model. Methods. After complete clinical evaluation, human tissue was removed at vitrectomy from patients with PDR (n=10), PVR (n=7) or subretinal neovascularization (SRNV; n=28) or post-mortem from normal donors (n=8). Frozen tissues were processed for immunofluorescence and stained with conformation-specific antisera to αvβ3, αv,β5 or vonWillebrand factor (VWF), a vascular endothelial cell marker. Results. All normal or PVR specimens were negative for either integrin. αv,β3 and VWF strictly co-localized in PDR or SRNV tissues; αvβ5, co-localized with VWF in PDR, but was also upregulated in nonvascular cellular components. Systemically administered peptide antagonists of αv,β3 and αvα5 inhibited retinal vasculature development in a mouse model; control peptides had no effect on retinal vessel growth. Conclusions. (1) integrins αv,β3, and αvβ5 are selectively expressed on actively proliferating blood vessels in human retinal and choroidal NV tissues and (2) systemic administration of peptide antagonists of these integrins inhibit the growth of retinal blood vessels in a mouse model. These results are consistent with a role for αvβ3 and αvβ5 in retinal and choroidal angiogenesis and suggest that antagonists of these integrins may be useful therapeutics for inhibiting ocular NV.
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