title: Effects of intravitreally injected Fc fragment on rat eyes.
abstract: OBJECTIVE
  Anti-vascular endothelial growth factor (VEGF) drugs are used to treat neovascular eye diseases. Some of these drugs contain Fc fragments (Fc), but it is unknown how their mode of action is influenced by Fc. Therefore, this study investigated the effects of Fc on rat eyes after intravitreal injection.
  
  
  METHODS
  Eighteen Long-Evans rats were intravitreally injected with sterile, biotin-labeled rat Fc (9.1 μg in 5 μl PBS). For control, 5 μl PBS was injected in another nine rats. Animals were sacrificed between 1 and 3 days (group 1), 7 days (group 2), and 14 days (group 3) after injection. The right eyes were examined by electron microscopy (EM). The left eyes were stained by immunohistochemistry to investigate the distribution of Fc and the presence of macrophages.
  
  
  RESULTS
  After 1 day, Fc had penetrated into the anterior chamber and the retina up to the inner nuclear layer, and was located especially in retinal vessels. High numbers of infiltrating cells were present within the vitreous, around the ciliary body, anterior chamber and inside the retina 1-3 days after Fc injection (p < 0.02 group 1 vs. control). Immunohistochemistry and EM showed that they were macrophages or granulocytes in close association with Fc. Ultrastructurally, there were effects on the blood vessels such as thrombocyte activation and fibrin formation.
  
  
  CONCLUSIONS
  Biotin labeling is ideal for investigating the distribution of intravitreally injected proteins in ocular tissue. Fc fragments at a dose corresponding to their concentration in standard AMD treatments induced inflammation, and particularly the attraction of immune-competent cells. This may be associated with the risk of inflammation or endophthalmitis after anti-VEGF treatment, and needs further investigation.
authors.affiliation: Centre for Ophthalmology, Division of Experimental Vitreoretinal Surgery, Schleichstrasse 12/1, Tuebingen, Germany.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Taubitz
authors.affiliation: Centre for Ophthalmology, Division of Experimental Vitreoretinal Surgery, Schleichstrasse 12/1, Tuebingen, Germany.
authors.forename: Laura-Pia
authors.initials: LP
authors.lastname: Steinbrenner
authors.affiliation: Centre for Ophthalmology, Division of Experimental Vitreoretinal Surgery, Schleichstrasse 12/1, Tuebingen, Germany.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Tschulakow
authors.affiliation: Centre for Ophthalmology, Division of Experimental Vitreoretinal Surgery, Schleichstrasse 12/1, Tuebingen, Germany. antje.biesemeier@med.uni-tuebingen.de.
authors.forename: Antje
authors.initials: A
authors.lastname: Biesemeier
authors.affiliation: Centre for Ophthalmology, Division of Experimental Vitreoretinal Surgery, Schleichstrasse 12/1, Tuebingen, Germany.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Julien-Schraermeyer
authors.affiliation: Centre for Ophthalmology, Division of Experimental Vitreoretinal Surgery, Schleichstrasse 12/1, Tuebingen, Germany.|STZ OcuTox Preclinical Drug Assessment, Hechingen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schraermeyer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D009877:Endophthalmitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000008:administration & dosage; D058449:Intravitreal Injections; D008854:Microscopy, Electron; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D007141:Immunoglobulin Fc Fragments; D007155:Immunologic Factors; D042461:Vascular Endothelial Growth Factor A
keywords: Anti-VEGF therapy; Endophthalmitis; Fc fragment; Intravitreal injection