title: Effect of Penetrating Keratoplasty and Keratoprosthesis Implantation on the Posterior Segment of the Eye.
abstract: OBJECTIVE
  To compare the effects of post-penetrating keratoplasty (PK) and post-keratoprosthesis (KPro) surgery-related inflammation on the posterior segment of the eye and to assess inhibition of tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β) on these effects.
  
  
  METHODS
  BALB/C (syngeneic) or C57BL/6 (allogeneic) corneas were transplanted onto BALB/C host beds as part of PK or miniature KPro (m-KPro) implantation. Intraocular pressure (IOP) was measured via an intracameral pressure sensor; tissues were harvested and analyzed 8 weeks after surgery. Expression of TNFα and IL-1β in the retina was analyzed using real-time quantitative (q)PCR. Optic nerve degeneration (axon count, circularity, and area) was assessed quantitatively using ImageJ software. After m-KPro implantation, mice were treated with saline, anti-TNFα, or anti-IL-1β antibody, and axonal loss was assessed after 10 weeks.
  
  
  RESULTS
  Mean IOP was within normal limits in the operated and fellow eyes in all groups. The mRNA expression of TNFα and IL-1β was highest in m-KPro groups with either syngeneic or an allogeneic carrier. We observed optic nerve degeneration in both allogeneic PK and m-KPro implanted eyes with an allogeneic carrier. However, TNFα blockade significantly reduced axonal loss by 35%.
  
  
  CONCLUSIONS
  Allogeneic PK and m-KPro implants with an allogeneic carrier lead to chronic inflammation in the posterior segment of the eye, resulting in optic nerve degeneration. In addition, blockade of TNFα prevents axonal degeneration in this preclinical model of allogeneic m-KPro (alloKPro) implantation.
authors.forename: Alja
authors.initials: A
authors.lastname: Črnej
authors.forename: Masahiro
authors.initials: M
authors.lastname: Omoto
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Dohlman
authors.forename: Miguel
authors.initials: M
authors.lastname: Gonzalez-Andrades
authors.forename: Eleftherios I
authors.initials: EI
authors.lastname: Paschalis
authors.forename: Andrea
authors.initials: A
authors.lastname: Cruzat
authors.forename: T H Khanh
authors.initials: TH
authors.lastname: Vu
authors.forename: Marianne
authors.initials: M
authors.lastname: Doorenbos
authors.forename: Dong Feng
authors.initials: DF
authors.lastname: Chen
authors.forename: Claes H
authors.initials: CH
authors.lastname: Dohlman
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
mesh_terms: D000818:Animals; D001187:Artificial Organs; D001369:Axons / Q000473:pathology; D001705:Bioprosthesis / Q000009:adverse effects*; D003315:Cornea; D015870:Gene Expression / Q000502:physiology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics; D007429:Intraocular Pressure; D015948:Keratoplasty, Penetrating / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D009901:Optic Nerve Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D057972:Posterior Eye Segment / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha