title: Evaluation of the human choroidal melanoma rabbit model for studying microcirculation patterns with confocal ICG and histology.
abstract: The aim of this study was to develop consistently focal elevated choroidal masses of human choroidal melanoma in immunosuppressed rabbits and to correlate the visualization of prognostically significant microcirculation patterns from confocal indocyanine green angiography with histologic microcirculation patterns. A human choroidal melanoma cell line (OCM1) was implanted in the choroid of 40 rabbit eyes using three different techniques: transscleral choroidal injection of a cell suspension, injection of a cell suspension in a surgically induced cyclodialysis cleft, and implantation of solid tumor fragments in a surgically induced cyclodialysis cleft. The rabbits were immunosuppressed with daily injections of Cyclosporin A to prevent host versus graft reaction. The eyes were studied weekly with indirect ophthalmoscopy and fundus photography to monitor tumor growth and indocyanine green angiography using a confocal scanning laser ophthalmoscope to identify microcirculation patterns in vivo and correlate these findings with the histologic demonstration of tumor microcirculation patterns. A tumor mass was identified by indirect ophthalmoscopy in 16 of the 40 implanted rabbit eyes (40%). Each of these tumors was confirmed histologically to represent a focal elevated choroidal mass. All 16 elevated choroidal masses grow in eyes in which solid tumor fragments were implanted. In total, a melanoma was identified histologically in 28 of the implanted 40 eyes (70%). In addition to the 16 eyes where the melanoma appeared as a focal elevated choroidal mass, 4 eyes contained a focal elevated mass in the sclera and 8 eyes contained a flat choroidal tumor. Histologically, microcirculation patterns were identified only in the 16 eyes with focal elevated choroidal masses. Confocal indocyanine green angiography imaged microcirculation patterns in 13 of these 16 eyes (81%). The surgical implantation of small solid fragments of human choroidal melanoma in immunosuppressed rabbit eyes provides the best method to consistently obtain focal elevated choroidal masses. These focal elevated choroidal masses resemble booth the localization and the growth pattern of choroidal melanomas in humans. In addition, they also contain microcirculation patterns similar to those seen in humans that are detectable with confocal indocyanine green angiography. The use of indocyanine green angiography with this animal model may be especially useful in designing and evaluating anti-microcirculation treatments directed at uveal melanoma.
authors.affiliation: Department of Ophthalmology, Shiley Eye Center, University of California, San Diego, 9415 Campus Point Dr., La Jolla, CA, 92093-0946, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Mueller
authors.forename: R
authors.initials: R
authors.lastname: Folberg
authors.forename: W R
authors.initials: WR
authors.lastname: Freeman
authors.forename: D U
authors.initials: DU
authors.lastname: Bartsch
authors.forename: G
authors.initials: G
authors.lastname: Bergeron-Lynn
authors.forename: M G
authors.initials: MG
authors.lastname: Mehaffey
authors.forename: J
authors.initials: J
authors.lastname: Kan-Mitchell
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: G
authors.initials: G
authors.lastname: Jian
authors.forename: C
authors.initials: C
authors.lastname: Avila
authors.forename: I
authors.initials: I
authors.lastname: Taskintuna
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: J
authors.initials: J
authors.lastname: Wang
mesh_terms: D000792:Angiography; D000818:Animals; D002830:Choroid Neoplasms / Q000098:blood supply* / Q000473:pathology; D004396:Coloring Agents; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D006801:Humans; D016867:Immunocompromised Host; D007208:Indocyanine Green; D008545:Melanoma / Q000098:blood supply* / Q000473:pathology; D008833:Microcirculation / Q000000981:diagnostic imaging; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging; D011817:Rabbits; D014183:Transplantation, Heterologous
chemical_list: D004396:Coloring Agents; D007208:Indocyanine Green