title: Steroid differentiation: the safety profile of various steroids on retinal cells in vitro and their implications for clinical use (an American Ophthalmological Society thesis).
abstract: OBJECTIVE
  To determine if potentially viable alternatives to the clinical use of intravitreal triamcinolone acetonide should be considered based on a comparative assessment of the in vitro effects of five commercially available corticosteroids. We hypothesized that dexamethasone, betamethasone, methylprednisolone, loteprednol etabonate, and fluocinolone acetonide, at clinically relevant doses, may show different levels of in vitro cytotoxicity to retinal cells.
  
  
  METHODS
  Cultures of human retinal pigment epithelial cells (ARPE-19) and rat embryonal neurosensory precursor retinal cells (R28) were treated with dexamethasone, betamethasone, methylprednisolone, loteprednol, or fluocinolone acetonide. Cell viability as a measure of cell death was determined by trypan blue dye exclusion assay. The mechanical effect of drug crystals was evaluated by solubilizing the steroid formulations. Mitochondrial dehydrogenase and membrane potential were assessed to measure cell damage.
  
  
  RESULTS
  Betamethasone, loteprednol, and methylprednisolone, in commercially available forms, caused significant cytotoxic changes to retinal cells in vitro at clinically relevant doses. This effect was less pronounced with solubilized betamethasone. Dexamethasone at concentrations up to 5 times the clinical dose of free drug injections and 1000 times greater than a drug implant did not cause decreased cell viability. Fluocinolone acetonide at doses 1000 times higher than observed with drug delivery systems showed no cytotoxic effect.
  
  
  CONCLUSIONS
  Betamethasone, loteprednol, and methylprednisolone exhibited cytotoxicity at clinically relevant doses and do not appear to be good therapeutic options for intravitreal use. In comparison, dexamethasone and fluocinolone acetonide, which exhibited fewer cytotoxic effects than other steroids, may be potentially viable alternatives to triamcinolone acetonide for clinical use.
authors: Gavin Herbert Eye Institute, Department of Ophthalmology, University of California Irvine, Irvine, California.
authors: Baruch D
authors: BD
authors: Kuppermann
authors: Department of Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil.
authors: Leandro Cabral
authors: LC
authors: Zacharias
authors: Gavin Herbert Eye Institute, Department of Ophthalmology, University of California Irvine, Irvine, California.
authors: M Cristina
authors: MC
authors: Kenney
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects*
chemical_list: D000305:Adrenal Cortex Hormones; D010088:Oxidoreductases
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