International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 184 - FUNCTIONAL ANALYSIS OF THE HYALOID MICROCIRCULATION IN A MOUSE MODEL OF RETINOBLASTOMA

Duckett AS, Leamen L, Cucevic V, Foster FS

Sunnybrook and Womens College Health Sciences Centre,  University of Toronto, Toronto, Canada

High resolution micro imaging tools have enabled non invasive visualization of tissue remodelling in longitudinal studies of the mouse. In mice, the hyaloid vasculature of the eye degenerates from a well defined structure at birth via progressive loss of branching structure.  Hyaloid regression is accompanied through a complex and poorly understood process by retinal vascular maturation.  Until the present it has not been possible to study ocular vascular patterning noninvasively.  Recently developed high frequency ultrasound microimaging (UBM) is well suited for the study of this process because the vascular networks of eye are comparativley superficial and are in juxtaposition to the echolucent tissues of the vitreous and lens. Flow is easily measured in the hyaloid artery (HA), vasa hyaloidea propria (VHP), and tunica vasculosa lentis (TVL), and retina.  In this study, flow waveforms at all 4 locations were measured in normal CD-1 and LHbTAg (retinoblastoma) mice over the period from birth  to 4.5 months.  Ultrasound imaging and Doppler were performed with a Vevo 660 (VisualSonics,Toronto) mouse scanner. Contrast enhanced MicroCT was used as a gold standard for vessel structure and was performed with an MS8 scanner (EVS (now  General Electric), London Ontario).  All imaging was performed under an approved animal protocol.  Observations of normal mice showed marked remodeling of the hyaloid vasculature over the first 16 days.  Peak flow velocities in the hyaloid artery dropped from 3.0 ± 1.0 cm/s to 0 between P0 and P13 while peak velocities in the VHP and TVL dropped from 1.25 ± .25 cm/s to 0 from P0 to P13.  No flow or evidence of a hyaloid vasculature was observed in the control mice after P13. Flow in the retinal vasculature showed an inversely proportional increase from 0.3 ± .05 cm/s to 4.1 ± 0.6 cm/s over the same time period.  In the retinoblastoma mice intraocular tumours were visible at 2 months and by 4.5 months had filled the vitreous cavity.  The blood supply for these tumours is demonstrated to be derived from a persistent and significantly augmented hyaloid vasculature. Conclusion:  Functional flow patterns of the hyaloid vasculature is result from a sensitive balance of angiogenic and apoptotic factors and appear to be inversely proportional to flow in the retinal circulation.  Flow in the hyaloid circulation does not normally persist beyond P13. Ocular tumours in a spontaneous model of retinoblastoma appear to recruit and expand the hyaloid vasculature to sustain an aggressive growth pattern.

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