title: Differential sensitivity of choroidal endothelial, retinal ganglion, and retinal pigment epithelial cells in vitro to proton radiation.
abstract: OBJECTIVE
  To evaluate the differential sensitivity of choroidal endothelial, retinal pigment epithelial, and retinal ganglion cells to escalating doses of proton beam radiation and to establish a safe dose range for the management of choroidal neovascularization associated with age-related macular degeneration (AMD).
  
  
  METHODS
  Laboratory investigation.
  
  
  METHODS
  Proliferating simian choroidal endothelial cells (RF/6A), differentiated rat retinal ganglion cells (RGC-5), and serum-starved human retinal pigment epithelial cells (ARPE-19) were exposed to 2, 4, 8, and 12 cobalt gray equivalent of proton beam radiation and cell viability was quantified on day 9. Reactive oxygen species levels were analyzed.
  
  
  RESULTS
  Significant decline of choroidal endothelial cell viability was noted as dose escalated from 4 to 8 cobalt gray equivalent with maximum effect observed at 12 cobalt gray equivalent. RGC-5 and ARPE-19 cell count decreased to 95% and 62.7% at 8 cobalt gray equivalent, respectively. Sub-analysis between 4 and 8 cobalt gray equivalent radiation revealed significant decrease in choroidal endothelial cell viability (43.1% at 7 cobalt gray equivalent and 32.3% at 8 cobalt gray equivalent of radiation). Correspondingly, RGC-5 and ARPE-19 cells did not show decrease in cell count or viability. Reactive oxygen species levels significantly increased in radiation-treated choroidal endothelial cells (8.3%-11.9%).
  
  
  CONCLUSIONS
  At 6-8 cobalt gray equivalent proton beam radiation, retinal ganglion and retinal pigment epithelial cells are preserved while choroidal endothelial cells are completely inhibited. This dosage offers optimum therapeutic safety window for treatment using proton beam radiation for exudative AMD.
authors.affiliation: Department of Ophthalmology, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Sankarathi
authors.initials: S
authors.lastname: Balaiya
authors.affiliation: Department of Ophthalmology, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Murthy
authors.affiliation: University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Robert
authors.initials: R
authors.lastname: Malyapa
authors.affiliation: Department of Ophthalmology, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Grover
authors.affiliation: Department of Ophthalmology, University of Florida College of Medicine, Jacksonville, Florida. Electronic address: kchalam@jax.ufl.edu.
authors.forename: Kakarla V
authors.initials: KV
authors.lastname: Chalam
mesh_terms: D000818:Animals; D002452:Cell Count; D002460:Cell Line; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival; D002829:Choroid / Q000098:blood supply*; D004307:Dose-Response Relationship, Radiation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D008251:Macaca; D061766:Proton Therapy; D011829:Radiation Dosage; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*
chemical_list: D017382:Reactive Oxygen Species