title: Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma.
abstract: OBJECTIVE
  Retinoblastoma is the most common primary intraocular malignancy in children. Although significant advances in treatment have decreased mortality in recent years, morbidity continues to be associated with these therapies, and therefore, there is a pressing need for new therapeutic options. Transgenic mouse models are popular for testing new therapeutics as well as studying the pathophysiology of retinoblastoma. The T-antigen retinoblastoma (TAg-RB) model has close molecular and histological resemblance to human retinoblastoma tumors; these mice inactivate pRB by retinal-specific expression of the Simian Virus 40 T-antigens. Here, we evaluated whether optical coherence tomography (OCT) imaging could be used to document tumor growth in the TAg-RB model from the earliest stages of tumor development.
  
  
  METHODS
  The Micron III rodent imaging system was used to obtain fundus photographs and OCT images of both eyes of TAg-RB mice weekly from 2 to 12 weeks of age and at 16 and 20 weeks of age to document tumor development. Tumor morphology was confirmed with histological analysis.
  
  
  RESULTS
  Before being visible on funduscopy, hyperreflective masses arising in the inner nuclear layer were evident at 2 weeks of age with OCT imaging. After most of these hyperreflective cell clusters disappeared around 4 weeks of age, the first tumors became visible on OCT and funduscopy by 6 weeks. The masses grew into discrete, discoid tumors, preferentially in the periphery, that developed more irregular morphology over time, eventually merging and displacing the inner retinal layers into the vitreous.
  
  
  CONCLUSIONS
  OCT is a non-invasive imaging modality for tracking early TAg-RB tumor growth in vivo. Using OCT, we characterized TAg-positive cells as early as 2 weeks, corresponding to the earliest stages at which tumors are histologically evident, and well before they are evident with funduscopy. Tracking tumor growth from its earliest stages will allow better analysis of the efficacy of novel therapeutics and genetic factors tested in this powerful mouse model.
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Wenzel
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN ; School of Biomedical Science, University of Ulster, Coleraine, Northern Ireland, UK.
authors.forename: Michael N
authors.initials: MN
authors.lastname: O'Hare
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shadmand
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN ; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN ; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN ; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Corson
mesh_terms: D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D005654:Fundus Oculi; D055786:Gene Knockout Techniques; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D019572:Retinal Neoplasms / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D012175:Retinoblastoma / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors / Q000235:genetics; D041623:Tomography, Optical Coherence
chemical_list: D000957:Antigens, Viral, Tumor; D016160:Retinoblastoma Protein