DEVELOPMENT AND CHARACTERIZATION OF A PRECLINICAL MODEL OF DISSEMINATED RETINOBLASTOMA

GUILLERMO CHANTADA; JUAN OSCAR CROXATTO; MARÍA DEL ROSARIO ASCHERO; PAULA SCHAIQUEVICH; ÁNGEL MONTERO CARCABOSO; ANA TORBIDONI; SANTIAGO ZUGBI; OSVALDO PODHAJCER; EDUARDO CAFFERATA; URSULA WINTER

Congreso; Reunión Conjunta Anual de Sociedades de Biociencias; 2017

In the absence of prompt diagnosis and appropriatetreatment,retinoblastomadisseminates outside of the ocularglobe. In lower-income countries, patients more oftenpresentwith disseminated disease at the time of diagnosis.These patients receive an empirical and aggressive formof chemotherapy treatment, but still, fatal outcomes areobserved. Currently, there is no second line of treatmentand so disseminated retinoblastoma is considered an unmetmedical need.There are no previous reports of any type of animal modelfordisseminated retinoblastoma. In order to study the tumorbiologyand new or alternative pharmacological treatments weneed an adequate preclinical model that still is notavailable.Thus, ouraimwas to develop an animal model that closelyresembles the patient´s condition.The protocol (#838) was approved by the local IRB. The cellmodel (396LNP) was derived from a unilateral patient withdisseminated retinoblastoma in the cervical lymph node.These cells were injected into the posterior segment of theeye in 6-week old athymic mice. The animals were observed tillthe tumor invaded the ocular globe causing proptosis.The mice were then enucleated and sacrificed. Eyes wereconserved for histopathological studies. Tissue sampleswerecollected to assess for retinoblastomadisseminationquantifyingthespecific lineage molecular markerCRXby means ofRT-qPCR.A total of 19 eyes were injected with 396LNP cells with a79%of engraftment. The eye survival was 23 days. In3 of15animalscells disseminated into the lymph nodes and in7/15optic nerves which resembled the patient´s condition. Allthebone marrow samples were negative for CRX.We have established a new disseminated RB animal modelfor the study of metastatic disease. This animal can beused to evaluate more advanced and efficient alternativetreatment options.It will also allow for the development ofapre-clinical research platform which can later be appliedfortranslational studies.Keywords: Disseminated Retinoblastoma, preclinical model,metastasis